Clinical trial - Knowledge

1307:

reasoning behind this discovery may be patients are happy with their current care. Another reason for the negative relationship between perceived fairness and clinical trial enrollment is the lack of independence from the care provider. Results found that there is a positive relationship between a lack of willingness to talk with their doctor and clinical trial enrollment. Lack of willingness to talk about clinical trials with current care providers may be due to patients' independence from the doctor. Patients who are less likely to talk about clinical trials are more willing to use other sources of information to gain a better insight of alternative treatments. Clinical trial enrollment should be motivated to utilize websites and television advertising to inform the public about clinical trial enrollment.

302:(PPI). Public involvement involves a working partnership between patients, caregivers, people with lived experience, and researchers to shape and influence what is researcher and how. PPI can improve the quality of research and make it more relevant and accessible. People with current or past experience of illness can provide a different perspective than professionals and compliment their knowledge. Through their personal knowledge they can identify research topics that are relevant and important to those living with an illness or using a service. They can also help to make the research more grounded in the needs of the specific communities they are part of. Public contributors can also ensure that the research is presented in 40: 1122: 1763:(IEC), is necessary before all but the most informal research can begin. In commercial clinical trials, the study protocol is not approved by an IRB before the sponsor recruits sites to conduct the trial. However, the study protocol and procedures have been tailored to fit generic IRB submission requirements. In this case, and where there is no independent sponsor, each local site investigator submits the study protocol, the consent(s), the data collection forms, and supporting documentation to the local IRB. Universities and most hospitals have in-house IRBs. Other researchers (such as in walk-in clinics) use independent IRBs. 1226:

find the appropriate patients and obtain their consent, especially when they may receive no direct benefit (because they are not paid, the study drug is not yet proven to work, or the patient may receive a placebo). In the case of cancer patients, fewer than 5% of adults with cancer will participate in drug trials. According to the Pharmaceutical Research and Manufacturers of America (PhRMA), about 400 cancer medicines were being tested in clinical trials in 2005. Not all of these will prove to be useful, but those that are may be delayed in getting approved because the number of participants is so low.

1591:

trials. Inclusion of children in clinical trials has additional moral considerations, as children lack decision-making autonomy. Trials in the past had been criticized for using hospitalized children or orphans; these ethical concerns effectively stopped future research. In efforts to maintain effective pediatric care, several European countries and the US have policies to entice or compel pharmaceutical companies to conduct pediatric trials. International guidance recommends ethical pediatric trials by limiting harm, considering varied risks, and taking into account the complexities of pediatric care.

10728: 2030: 1202:

drugs are tested before just one reaches the point of being tested in a clinical trial. For example, a new cancer drug has, on average, six years of research behind it before it even makes it to clinical trials. But the major holdup in making new cancer drugs available is the time it takes to complete clinical trials themselves. On average, about eight years pass from the time a cancer drug enters clinical trials until it receives approval from regulatory agencies for sale to the public. Drugs for other diseases have similar timelines.

1904:, offer grants to investigators who design clinical trials that attempt to answer research questions of interest to the agency. In these cases, the investigator who writes the grant and administers the study acts as the sponsor, and coordinates data collection from any other sites. These other sites may or may not be paid for participating in the study, depending on the amount of the grant and the amount of effort expected from them. Using internet resources can, in some cases, reduce the economic burden. 1806:

management. Different countries have different regulatory requirements and enforcement abilities. An estimated 40% of all clinical trials now take place in Asia, Eastern Europe, and Central and South America. "There is no compulsory registration system for clinical trials in these countries and many do not follow European directives in their operations", says Jacob Sijtsma of the Netherlands-based WEMOS, an advocacy health organisation tracking clinical trials in developing countries.

1814:(ICH) Currently, most clinical trial programs follow ICH guidelines, aimed at "ensuring that good quality, safe and effective medicines are developed and registered in the most efficient and cost-effective manner. These activities are pursued in the interest of the consumer and public health, to prevent unnecessary duplication of clinical trials in humans and to minimize the use of animal testing without compromising the regulatory obligations of safety and effectiveness." 10714: 493: 1669: 1194: 320: 10752: 926: 1922:

motivations such as contributing to science and others. In later phase trials, subjects may not be paid to ensure their motivation for participating with potential for a health benefit or contributing to medical knowledge. Small payments may be made for study-related expenses such as travel or as compensation for their time in providing follow-up information about their health after the trial treatment ends.

10740: 146:

intended to be used, what other treatments are available, and the severity of the disease or condition. The benefits must outweigh the risks. For example, many drugs to treat cancer have severe side effects that would not be acceptable for an over-the-counter pain medication, yet the cancer drugs have been approved since they are used under a physician's care and are used for a life-threatening condition.

785: 1823:

regulatory agencies to monitor the aggregate safety profile of experimental medicines as they are developed. The value of assessing aggregate safety data is: a) decisions based on aggregate safety assessment during development of the medicine can be made throughout the medicine's development and b) it sets up the sponsor and regulators well for assessing the medicine's safety after the drug is approved.

3725: 1290:(IRB) with the documentation necessary to obtain its permission to conduct the study, assisting with study start-up, identifying eligible patients, obtaining consent from them or their families, administering study treatment(s), collecting and statistically analyzing data, maintaining and updating data files during followup, and communicating with the IRB, as well as the sponsor and CRO. 1377:

available for analysis while subjects are still being assigned to treatment groups in the trial. Early analysis may allow the emerging evidence to assist decisions about whether to stop the study, or to reassign participants to the more successful segment of the trial. Investigators may also want to stop a trial when data analysis shows no treatment effect.

1931: 1735:("first, do no harm") guides the trial, and if an investigator believes the study treatment may be harming subjects in the study, the investigator can stop participating at any time. On the other hand, investigators often have a financial interest in recruiting subjects, and could act unethically to obtain and maintain their participation. 1044:, which includes varying genetic disruptions from patient to patient. Amgen, AstraZeneca and Pfizer are involved, the first time they have worked together in a late-stage trial. Patients whose genomic profiles do not match any of the trial drugs receive a drug designed to stimulate the immune system to attack cancer. 433:. The treatment of group five stopped after six days when they ran out of fruit, but by then one sailor was fit for duty while the other had almost recovered. Apart from that, only group one also showed some effect of its treatment. Each year, May 20 is celebrated as Clinical Trials Day in honor of Lind's research. 1136:". The document includes details such as its purpose, duration, required procedures, risks, potential benefits, key contacts and institutional requirements. The participant then decides whether to sign the document. The document is not a contract, as the participant can withdraw at any time without penalty. 354:, arranged for seven prisoners who had been sentenced to death to undergo variolation in exchange for their life. Although they survived and did not contract smallpox, there was no control group to assess whether this result was due to the inoculation or some other factor. Similar experiments performed by 1987:

It has been observed that participants in clinical trials are disproportionately white. Often, minorities are not informed about clinical trials. One recent systematic review of the literature found that race/ethnicity as well as sex were not well-represented nor at times even tracked as participants

1801:

any study of a drug, biological product or device in humans submitted in a marketing application or reclassification petition that the applicant or FDA relies on to establish that the product is effective (including studies that show equivalence to an effective product) or any study in which a single

1766:

The IRB scrutinizes the study both for medical safety and for protection of the patients involved in the study, before it allows the researcher to begin the study. It may require changes in study procedures or in the explanations given to the patient. A required yearly "continuing review" report from

1746:

When a local investigator is the sponsor, there may not be formal adverse event reports, but study staff at all locations are responsible for informing the coordinating investigator of anything unexpected. The local investigator is responsible for being truthful to the local IRB in all communications

1411:

of participating human subjects. (One of the IRB's main functions is to ensure potential patients are adequately informed about the clinical trial.) If the patient is unable to consent for him/herself, researchers can seek consent from the patient's legally authorized representative. In addition, the

1357:

I trial that used telemonitoring, also known as remote patient monitoring, to collect biometric data in patients' homes and transmit it electronically to the trial database. This technology provides many more data points and is far more convenient for patients, because they have fewer visits to trial

1260:

Clinical trials designed by a local investigator, and (in the US) federally funded clinical trials, are almost always administered by the researcher who designed the study and applied for the grant. Small-scale device studies may be administered by the sponsoring company. Clinical trials of new drugs

1028:

A master protocol includes multiple substudies, which may have different objectives and involve coordinated efforts to evaluate one or more medical products in one or more diseases or conditions within the overall study structure. Trials that could develop a master protocol include the umbrella trial

1006:

Clinical studies can be "sponsored" (financed and organized) by academic institutions, pharmaceutical companies, government entities and even private groups. Trials are conducted for new drugs, biotechnology, diagnostic assays or medical devices to determine their safety and efficacy prior to being

1783:

the files of local site investigators after they have finished participating in a study, to see if they were correctly following study procedures. This audit may be random, or for cause (because the investigator is suspected of fraudulent data). Avoiding an audit is an incentive for investigators to

1323:

are often used by research sponsors or CROs to help plan and manage the operational aspects of a clinical trial, particularly with respect to investigational sites. Advanced analytics for identifying researchers and research sites with expertise in a given area utilize public and private information

1216:

Only certain people who have the target disease condition are eligible to take part in each clinical trial. Researchers who treat these particular patients must participate in the trial. Then they must identify the desirable patients and obtain consent from them or their families to take part in the

1015:

In cases where giving a placebo to a person suffering from a disease may be unethical, "active comparator" (also known as "active control") trials may be conducted instead. In trials with an active control group, subjects are given either the experimental treatment or a previously approved treatment

655:, the investigators give the research subjects an experimental drug, surgical procedure, use of a medical device, diagnostic or other intervention to compare the treated subjects with those receiving no treatment or the standard treatment. Then the researchers assess how the subjects' health changes. 1809:

Beginning in the 1980s, harmonization of clinical trial protocols was shown as feasible across countries of the European Union. At the same time, coordination between Europe, Japan and the United States led to a joint regulatory-industry initiative on international harmonization named after 1990 as

1599:

Responsibility for the safety of the subjects in a clinical trial is shared between the sponsor, the local site investigators (if different from the sponsor), the various IRBs that supervise the study, and (in some cases, if the study involves a marketable drug or device), the regulatory agency for

1537:

Conducting clinical trials of vaccines during epidemics and pandemics is subject to ethical concerns. For diseases with high mortality rates like Ebola, assigning individuals to a placebo or control group can be viewed as a death sentence. In response to ethical concerns regarding clinical research

1395:

Clinical trials are closely supervised by appropriate regulatory authorities. All studies involving a medical or therapeutic intervention on patients must be approved by a supervising ethics committee before permission is granted to run the trial. The local ethics committee has discretion on how it

1225:

The biggest barrier to completing studies is the shortage of people who take part. All drug and many device trials target a subset of the population, meaning not everyone can participate. Some drug trials require patients to have unusual combinations of disease characteristics. It is a challenge to

2081:

Although trials are commonly conducted at major medical centers, some participants are excluded due to the distance and expenses required for travel, leading to hardship, disadvantage, and inequity for participants, especially those in rural and underserved communities. Therefore, the concept of a

2037:

The risk information seeking and processing (RISP) model analyzes social implications that affect attitudes and decision making pertaining to clinical trials. People who hold a higher stake or interest in the treatment provided in a clinical trial showed a greater likelihood of seeking information

1738:

The local investigators are responsible for conducting the study according to the study protocol, and supervising the study staff throughout the duration of the study. The local investigator or his/her study staff are also responsible for ensuring the potential subjects in the study understand the

1500:

cancer research. Similarly, competition for tenured academic positions, government grants and prestige create conflicts of interest among academic scientists. According to one study, approximately 75% of articles retracted for misconduct-related reasons have no declared industry financial support.

1376:

are used to determine whether such differences are true, result from chance, or are the same as no treatment (placebo). Data from a clinical trial accumulate gradually over the trial duration, extending from months to years. Accordingly, results for participants recruited early in the study become

1201:

Clinical trials are only a small part of the research that goes into developing a new treatment. Potential drugs, for example, first have to be discovered, purified, characterized, and tested in labs (in cell and animal studies) before ever undergoing clinical trials. In all, about 1,000 potential

882:

Phase II-a is specifically designed to assess dosing requirements (how much drug should be given), while a Phase II-b trial is designed to determine efficacy (100–300 people), assessing how well the drug works at the prescribed dose(s) to establish a therapeutic dose range and monitor for possible

845:

Phase 0 trials are optional first-in-human trials. Single subtherapeutic doses of the study drug or treatment are given to a small number of subjects (typically 10 to 15) to gather preliminary data on the agent's pharmacodynamics (what the drug does to the body) and pharmacokinetics (what the body

765:

to assess the trial's progress. In some cases, trials have become an ongoing process that regularly adds and drops therapies and patient groups as more information is gained. The aim is to more quickly identify drugs that have a therapeutic effect and to zero in on patient populations for whom the

149:

In the US the elderly constitute 14% of the population, while they consume over one-third of drugs. People over 55 (or a similar cutoff age) are often excluded from trials because their greater health issues and drug use complicate data interpretation, and because they have different physiological

6174:

Klein, Harry; Mazor, Tali; Siegel, Ethan; Trukhanov, Pavel; Ovalle, Andrea; Vecchio Fitz, Catherine Del; Zwiesler, Zachary; Kumari, Priti; Van Der Veen, Bernd; Marriott, Eric; Hansel, Jason; Yu, Joyce; Albayrak, Adem; Barry, Susan; Keller, Rachel B.; MacConaill, Laura E.; Lindeman, Neal; Johnson,

1822:

Aggregating safety data across clinical trials during drug development is important because trials are generally designed to focus on determining how well the drug works. The safety data collected and aggregated across multiple trials as the drug is developed allows the sponsor, investigators and

1654:

that accurately informs the potential subjects of the true risks and potential benefits of participating in the study, while at the same time presenting the material as briefly as possible and in ordinary language. FDA regulations state that participating in clinical trials is voluntary, with the

1528:

warned of the persistence of a gap in the credibility of conclusions arising from industry-funded clinical trials, and called for ensuring strict adherence to ethical standards in industrial collaborations with academia, in order to avoid further erosion of the public's trust. Issues referred for

1455:

Ethically balancing the rights of multiple stakeholders may be difficult. For example, when drug trials fail, the sponsors may have a duty to tell current and potential investors immediately, which means both the research staff and the enrolled participants may first hear about the end of a trial

990:

Blind: The subjects involved in the study do not know which study treatment they receive. If the study is double-blind, the researchers also do not know which treatment a subject receives. This intent is to prevent researchers from treating the two groups differently. A form of double-blind study

1590:

epidemic, a scientist noted that by excluding these groups from potentially life-saving treatment, they were being "protected to death". Projects such as Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) have advocated for the ethical inclusion of pregnant women in vaccine

1139:

Informed consent is a legal process in which a recruit is instructed about key facts before deciding whether to participate. Researchers explain the details of the study in terms the subject can understand. The information is presented in the subject's native language. Generally, children cannot

157:

The sponsor designs the trial in coordination with a panel of expert clinical investigators, including what alternative or existing treatments to compare to the new drug and what type(s) of patients might benefit. If the sponsor cannot obtain enough test subjects at one location investigators at

1912:

Investigators are often compensated for their work in clinical trials. These amounts can be small, just covering a partial salary for research assistants and the cost of any supplies (usually the case with national health agency studies), or be substantial and include "overhead" that allows the

1805:

Alternatively, many American pharmaceutical companies have moved some clinical trials overseas. Benefits of conducting trials abroad include lower costs (in some countries) and the ability to run larger trials in shorter timeframes, whereas a potential disadvantage exists in lower-quality trial

1742:

Local investigators are responsible for reviewing all adverse event reports sent by the sponsor. These adverse event reports contain the opinions of both the investigator (at the site where the adverse event occurred) and the sponsor, regarding the relationship of the adverse event to the study

1585:

Pregnant women and children are typically excluded from clinical trials as vulnerable populations, though the data to support excluding them is not robust. By excluding them from clinical trials, information about the safety and effectiveness of therapies for these populations is often lacking.

1306:

An Interactional Justice Model may be used to test the effects of willingness to talk with a doctor about clinical trial enrollment. Results found that potential clinical trial candidates were less likely to enroll in clinical trials if the patient is more willing to talk with their doctor. The

812:

or longer. If the drug successfully passes through phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population. Phase IV trials are performed after the newly approved drug, diagnostic or device is marketed, providing assessment about

404:

in 1747. He included a dietary supplement of an acidic quality in the experiment after two months at sea, when the ship was already afflicted with scurvy. He divided twelve scorbutic sailors into six groups of two. They all received the same diet but, in addition, group one was given a quart of

145:

There are two goals to testing medical treatments: to learn whether they work well enough, called "efficacy", or "effectiveness"; and to learn whether they are safe enough, called "safety". Neither is an absolute criterion; both safety and efficacy are evaluated relative to how the treatment is

1423:) law and good clinical practice. The International Conference of Harmonisation Guidelines for Good Clinical Practice is a set of standards used internationally for the conduct of clinical trials. The guidelines aim to ensure the "rights, safety and well being of trial subjects are protected". 2000:

Depending on the kind of participants required, sponsors of clinical trials, or contract research organizations working on their behalf, try to find sites with qualified personnel as well as access to patients who could participate in the trial. Working with those sites, they may use various

1624:

Throughout the clinical trial, the sponsor is responsible for accurately informing the local site investigators of the true historical safety record of the drug, device or other medical treatments to be tested, and of any potential interactions of the study treatment(s) with already approved

930: 969:, provide less compelling evidence than the randomized controlled trial. In observational studies, the investigators retrospectively assess associations between the treatments given to participants and their health status, with potential for considerable errors in design and interpretation. 1921:

Participants in Phase I drug trials do not gain any direct health benefit from taking part. They are generally paid a fee for their time, with payments regulated and not related to any risk involved. Motivations of healthy volunteers is not limited to financial reward and may include other

1512:

In 2001, the editors of 12 major journals issued a joint editorial, published in each journal, on the control over clinical trials exerted by sponsors, particularly targeting the use of contracts which allow sponsors to review the studies prior to publication and withhold publication. They

750:

trials provide partially tested, unapproved therapeutics to a small number of patients who have no other realistic options. Usually, this involves a disease for which no effective therapy has been approved, or a patient who has already failed all standard treatments and whose health is too

929: 933: 932: 927: 789: 1073:

The protocol contains a precise study plan to assure safety and health of the trial subjects and to provide an exact template for trial conduct by investigators. This allows data to be combined across all investigators/sites. The protocol also informs the study administrators (often a

787: 1811: 1083: 792: 791: 786: 934: 793: 1615:

For safety reasons, many clinical trials of drugs are designed to exclude women of childbearing age, pregnant women, or women who become pregnant during the study. In some cases, the male partners of these women are also excluded or required to take birth control measures.

1508:

In the United States, all clinical trials submitted to the FDA as part of a drug approval process are independently assessed by clinical experts within the Food and Drug Administration, including inspections of primary data collection at selected clinical trial sites.

1637:

data the sponsor has received so far. The DMC has the power to recommend termination of the study based on their review, for example if the study treatment is causing more deaths than the standard treatment, or seems to be causing unexpected and study-related serious

1336:

systems are used by sites to register the enrollment of patients using a phone and to allocate patients to a particular treatment arm (although phones are being increasingly replaced with web-based (IWRS) tools which are sometimes part of the EDC system). While

166:, concentration of the study drug in the blood or tissues, changes to symptoms, and whether improvement or worsening of the condition targeted by the study drug occurs. The researchers send the data to the trial sponsor, who then analyzes the pooled data using 1945:

Phase 0 and Phase I drug trials seek healthy volunteers. Most other clinical trials seek patients who have a specific disease or medical condition. The diversity observed in society should be reflected in clinical trials through the appropriate inclusion of

1002:

Clinical studies having small numbers of subjects may be "sponsored" by single researchers or a small group of researchers, and are designed to test simple questions or feasibility to expand the research for a more comprehensive randomized controlled trial.

4691:

Woolley KL, Lew RA, Stretton S, Ely JA, Bramich NJ, Keys JR, Monk JA, Woolley MJ (June 2011). "Lack of involvement of medical writers and the pharmaceutical industry in publications retracted for misconduct: a systematic, controlled, retrospective study".

931: 1281:

I clinical trials of new medicines are often conducted in a specialist clinical trial clinic, with dedicated pharmacologists, where the subjects can be observed by full-time staff. These clinics are often run by a CRO which specialises in these studies.

790: 1039:

enables researchers to group patients according to their genetic profile, deliver drugs based on that profile to that group and compare the results. Multiple companies can participate, each bringing a different drug. The first such approach targets

1081:

The format and content of clinical trial protocols sponsored by pharmaceutical, biotechnology or medical device companies in the United States, European Union, or Japan have been standardized to follow Good Clinical Practice guidance issued by the

760:

use existing data to design the trial, and then use interim results to modify the trial as it proceeds. Modifications include dosage, sample size, drug undergoing trial, patient selection criteria and "cocktail" mix. Adaptive trials often employ a

1212:

For drugs that are not expected to have a strong effect (meaning a large number of patients must be recruited to observe 'any' effect), recruiting enough patients to test the drug's effectiveness (i.e., getting statistical power) can take several

5508:"Investigational New Drug (IND) Application - Final Rule: Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products and Safety Reporting Requirements for Bioavailability and Bioequivalence Studies in Humans" 1160:-lowering drug versus placebo with 100 patients in each group might have a power of 0.90 to detect a difference between placebo and trial groups receiving dosage of 10 mg/dL or more, but only 0.70 to detect a difference of 6 mg/dL. 2008:

trials around the world to volunteers who have a specific set of criteria such as location, age, and symptoms. Other disease-specific services exist for volunteers to find trials related to their condition. Volunteers may search directly on

1495:

Drug researchers not directly employed by pharmaceutical companies often seek grants from manufacturers, and manufacturers often look to academic researchers to conduct studies within networks of universities and their hospitals, e.g., for

894:

Testing with large groups of people (typically 1,000–3,000) to confirm drug efficacy, evaluate its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow it to be used safely.

4629: 1065:

The protocol describes the scientific rationale, objective(s), design, methodology, statistical considerations and organization of the planned trial. Details of the trial are provided in documents referenced in the protocol, such as an

846:

does to the drugs). For a test drug, the trial documents the absorption, distribution, metabolization, and clearance (excretion) of the drug, and the drug's interactions within the body, to confirm that these appear to be as expected.

5515: 539:

of several independent factors. Of these, blocking and factorial design are seldom applied in clinical trials, because the experimental units are human subjects and there is typically only one independent intervention: the treatment.

1221:

A clinical trial might also include an extended post-study follow-up period from months to years for people who have participated in the trial, a so-called "extension phase", which aims to identify long-term impact of the treatment.

1358:

sites. As noted below, decentralized clinical trials are those that do not require patients' physical presence at a site, and instead rely largely on digital health data collection, digital informed consent processes, and so on.

2038:

about clinical trials. Cancer patients reported more optimistic attitudes towards clinical trials than the general population. Having a more optimistic outlook on clinical trials also leads to greater likelihood of enrolling.

1603:

A systematic concurrent safety review is frequently employed to assure research participant safety. The conduct and on-going review is designed to be proportional to the risk of the trial. Typically this role is filled by a

5247: 1796:

in the outcome of the study. For example, the applicant must disclose whether an investigator owns equity in the sponsor, or owns proprietary interest in the product under investigation. The FDA defines a covered study as

6017: 1529:

attention in this respect include potential observation bias, duration of the observation time for maintenance studies, the selection of the patient populations, factors that affect placebo response, and funding sources.

2001:

recruitment strategies, including patient databases, newspaper and radio advertisements, flyers, posters in places the patients might go (such as doctor's offices), and personal recruitment of patients by investigators.

161:

During the trial, investigators recruit subjects with the predetermined characteristics, administer the treatment(s) and collect data on the subjects' health for a defined time period. Data include measurements such as

2511: 1285:

At a participating site, one or more research assistants (often nurses) do most of the work in conducting the clinical trial. The research assistant's job can include some or all of the following: providing the local

554:

The first randomised curative trial was carried out at the MRC Tuberculosis Research Unit by Sir Geoffrey Marshall (1887–1982). The trial, carried out between 1946 and 1947, aimed to test the efficacy of the chemical

142:. Other clinical trials pertain to people with specific health conditions who are willing to try an experimental treatment. Pilot experiments are conducted to gain insights for design of the clinical trial to follow. 1437:. However, it may be hard to turn this objective into a well-defined, quantified, objective function. In some cases this can be done, however, for instance, for questions of when to stop sequential treatments (see 2050:

Manual: Healthcare providers or clinical trial coordinators manually review patient records and available trial criteria to identify potential matches. This might also include manually searching in clinical trial

2264: 5209: 1148:

In any clinical trial, the number of subjects, also called the sample size, has a large impact on the ability to reliably detect and measure the effects of the intervention. This ability is described as its

4893:

Mansi, Bernadette A.; Clark, Juli; David, Frank S.; Gesell, Thomas M.; Glasser, Susan; Gonzalez, John; Haller, Daniel G.; Laine, Christine; Miller, Charles L.; Mooney, LaVerne A.; Zecevic, Maja (May 2012).

6175:

Bruce E.; Rollins, Barrett J.; Do, Khanh T.; Beardslee, Brian; Shapiro, Geoffrey; Hector-Barry, Suzanne; Methot, John; Sholl, Lynette; Lindsay, James; Hassett, Michael J.; Cerami, Ethan (6 October 2022).

1646:

reports from all site investigators in the study, and for informing all the investigators of the sponsor's judgment as to whether these adverse events were related or not related to the study treatment.

1404:. Most IRBs are located at the local investigator's hospital or institution, but some sponsors allow the use of a central (independent/for profit) IRB for investigators who work at smaller institutions. 108:

Costs for clinical trials can range into the billions of dollars per approved drug, and the complete trial process to approval may require 7–15 years. The sponsor may be a governmental organization or a

1743:

treatments. Local investigators also are responsible for making an independent judgment of these reports, and promptly informing the local IRB of all serious and study treatment-related adverse events.

1988:

in a large number of clinical trials of hearing loss management in adults. This may reduce the validity of findings in respect of non-white patients by not adequately representing the larger population

3153:

Metcalfe NH (February 2011). "Sir Geoffrey Marshall (1887-1982): respiratory physician, catalyst for anaesthesia development, doctor to both Prime Minister and King, and World War I Barge Commander".

1847:

The cost of a study depends on many factors, especially the number of sites conducting the study, the number of patients involved, and whether the study treatment is already approved for medical use.

5807: 6237:

Yang ZJ, McComas KA, Gay GK, Leonard JP, Dannenberg AJ, Dillon H (2012). "Comparing decision making between cancer patients and the general population: thoughts, emotions, or social influence?".

5485: 1831:

Clinical trial costs vary depending on trial phase, type of trial, and disease studied. A study of clinical trials conducted in the United States from 2004 to 2012 found the average cost of Phase

5934: 928: 4636: 788: 770:

Clinical trials are conducted typically in four phases, with each phase using different numbers of subjects and having a different purpose to construct focus on identifying a specific effect.

5507: 3368: 2399:

Van Spall HG, Toren A, Kiss A, Fowler RA (March 2007). "Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review".

1433:

trials the latter becomes a particularly difficult problem. The final objective is to serve the community of patients or future patients in a best-possible and most responsible way. See also

1298:

In the context of a clinical trial, quality typically refers to the absence of errors which can impact decision making, both during the conduct of the trial and in use of the trial results.

4669: 2457: 1957:

All volunteers being considered for a trial are required to undertake a medical screening. Requirements differ according to the trial needs, but typically volunteers would be screened in a

3342: 3391: 751:

compromised to qualify for participation in randomized clinical trials. Usually, case-by-case approval must be granted by both the FDA and the pharmaceutical company for such exceptions.

204:. The protocol is the trial's "operating manual" and ensures all researchers perform the trial in the same way on similar subjects and that the data is comparable across all subjects. 4152: 1265:(CRO) hired by the sponsoring company. The sponsor provides the drug and medical oversight. A CRO is contracted to perform all the administrative work on a clinical trial. For Phases 1153:", which must be calculated before initiating a study to figure out if the study is worth its costs. In general, a larger sample size increases the statistical power, also the cost. 1016:

with known effectiveness. In other cases, sponsors may conduct an active comparator trial to establish an efficacy claim relative to the active comparator instead of the placebo in

3109:

Creswell, J.W. (2008). Educational research: Planning, conducting, and evaluating quantitative and qualitative research (3rd). Upper Saddle River, NJ: Prentice Hall. 2008, p. 300.

74:) and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received 5239: 2370: 2069:

methods to more effectively match patients to trials. These methods are faced with the challenge of overcoming the limitations of EHR records such as omissions and logging errors.

1156:

The statistical power estimates the ability of a trial to detect a difference of a particular size (or larger) between the treatment and control groups. For example, a trial of a

551:

to advise and assist in the arrangement of properly controlled clinical trials on new products that seem likely on experimental grounds to have value in the treatment of disease.

6013: 2623:

Farrokhyar F, Karanicolas PJ, Thoma A, Simunovic M, Bhandari M, Devereaux PJ, Anvari M, Adili A, Guyatt G (March 2010). "Randomized controlled trials of surgical interventions".

150:

capacity than younger people. Children and people with unrelated medical conditions are also frequently excluded. Pregnant women are often excluded due to potential risks to the

5605: 5576: 5544: 4004: 2507: 3218:"SearCh for humourIstic and Extravagant acroNyms and Thoroughly Inappropriate names For Important Clinical trials (SCIENTIFIC): qualitative and quantitative systematic study" 991:

called a "double-dummy" design allows additional insurance against bias. In this kind of study, all patients are given both placebo and active doses in alternating periods.

6291: 4840:

Davidoff F, DeAngelis CD, Drazen JM, Nicholls MG, Hoey J, Højgaard L, Horton R, Kotzin S, Nylenna M, Overbeke AJ, Sox HC, Van Der Weyden MB, Wilkes MS (September 2001).

1419:

In some US locations, the local IRB must certify researchers and their staff before they can conduct clinical trials. They must understand the federal patient privacy (

754:

Fixed trials consider existing data only during the trial's design, do not modify the trial after it begins, and do not assess the results until the study is completed.

2766: 89:, and subsequently conduct progressively larger scale comparative studies. Clinical trials can vary in size and cost, and they can involve a single research center or 5217: 3706: 2046:

Matching involves a systematic comparison of a patient's clinical and demographic information against the eligibility criteria of various trials. Methods include:

1989: 804:

Clinical trials involving new drugs are commonly classified into five phases. Each phase of the drug approval process is treated as a separate clinical trial. The

3743: 2791: 2072:

Direct-to-patient services: Resources are specialized to support patients in finding clinical trials through online platforms, hotlines, and personalized support.

2004:

Volunteers with specific conditions or diseases have additional online resources to help them locate clinical trials. For example, the Fox Trial Finder connects

1739:

risks and potential benefits of participating in the study. In other words, they (or their legally authorized representatives) must give truly informed consent.

4896:"Ten recommendations for closing the credibility gap in reporting industry-sponsored clinical research: a joint journal and pharmaceutical industry perspective" 3504: 1625:

treatments. This allows the local investigators to make an informed judgment on whether to participate in the study or not. The sponsor is also responsible for

1349:

is used to analyze the collected data and prepare them for regulatory submission. Access to many of these applications are increasingly aggregated in web-based

1174:

Merely giving a treatment can have nonspecific effects. These are controlled for by the inclusion of patients who receive only a placebo. Subjects are assigned

1062:

is a document used to define and manage the trial. It is prepared by a panel of experts. All study investigators are expected to strictly observe the protocol.

2057:(EHR). Some systems integrate with EHRs to automatically flag patients that may be eligible for trials based on their medical data. These systems may leverage 618:

the leader in the development in medicine of the precise experimental methods now used nationally and internationally in the evaluation of new therapeutic and

1033:(multiple products for a single disease entering and leaving the platform), and basket trial (one medical product for multiple diseases or disease subtypes). 4558: 4173:

Yang, Z. J., et al. (2010). "Motivation for Health Information Seeking and Processing About Clinical Trial Enrollment". Health Communication 25(5): 423–436.

2143: 1835:

I trials to be between $ 1.4 million and $ 6.6 million, depending on the type of disease. Phase II trials ranged from $ 7 million to $ 20 million, and Phase

1412:

clinical trial participants must be made aware that they can withdraw from the clinical trial at any time without any adverse action taken against them. In

1469: 1178:

without informing them to which group they belonged. Many trials are doubled-blinded so that researchers do not know to which group a subject is assigned.

484:; this organization collected data from physicians practicing outside the hospital setting and was the precursor of modern collaborative clinical trials." 246:. Device trials may compare a new device to an established therapy, or may compare similar devices to each other. An example of the former in the field of 5835: 1784:

follow study procedures. A 'covered clinical study' refers to a trial submitted to the FDA as part of a marketing application (for example, as part of an

857:

Often are first-in-person trials. Testing within a small group of people (typically 20–80) to evaluate safety, determine safe dosage ranges, and identify

4183: 2533:

Lederle FA, Freischlag JA, Kyriakides TC, Padberg FT, Matsumura JS, Kohler TR, Lin PH, Jean-Claude JM, Cikrit DF, Swanson KM, Peduzzi PN (October 2009).

2300: 1524:

Despite explicit recommendations by stakeholders of measures to improve the standards of industry-sponsored medical research, in 2013,

1420: 1099: 117:

or medical-device company. Certain functions necessary to the trial, such as monitoring and lab work, may be managed by an outsourced partner, such as a

5477: 5297: 4815: 274:

Similarly to drugs, medical or surgical procedures may be subjected to clinical trials, such as comparing different surgical approaches in treatment of

7302: 6583: 2082:"decentralized clinical trial" that minimizes or eliminates the need for patients to travel to sites, is now more widespread, a capability improved by 1629:

the results of the study as they come in from the various sites as the trial proceeds. In larger clinical trials, a sponsor will use the services of a

1445: 670:

trials look for ways to prevent disease in people who have never had the disease or to prevent a disease from returning. These approaches may include

8357: 4308: 1273:, sets up meetings, monitors the sites for compliance with the clinical protocol, and ensures the sponsor receives data from every site. Specialist 6104: 5926: 4208:

Life Sciences Strategy Group, "Clinical Trial Technology Utilization, Purchasing Preferences & Growth Outlook" Syndicated Publication, May 2009

3364: 4661: 2453: 2351: 1633:(DMC, known in the US as a data safety monitoring board). This independent group of clinicians and statisticians meets periodically to review the 4218: 3395: 3338: 3713:. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research. 21 December 2023. p. 1 1181:

Assigning a subject to a placebo group can pose an ethical problem if it violates his or her right to receive the best available treatment. The

9849: 7500: 2495: 2332: 294:

Besides being participants in a clinical trial, members of the public can be actively collaborate with researchers in designing and conducting

906:

Postmarketing studies delineate risks, benefits, and optimal use. As such, they are ongoing during the drug's lifetime of active medical use.

531:—to arrange experimental units into groups of units that are similar to each other, and thus reducing irrelevant sources of variation; use of 10354: 7389: 377:

deficiency, would often have terrible effects on the welfare of the crew of long-distance ocean voyages. In 1740, the catastrophic result of

4144: 2197:

Dimasi, Joseph A; Grabowski, Henry G; Hansen, Ronald W (2016). "Innovation in the pharmaceutical industry: New estimates of R&D costs".

2172: 1873:

communication with the local researchers, including on-site monitoring by the CRO before and (in some cases) multiple times during the study

7540: 7535: 5849:

McDonald AM, Knight RC, Campbell MK, Entwistle VA, Grant AM, Cook JA, Elbourne DR, Francis D, Garcia J, Roberts I, Snowdon C (April 2006).

5680: 3199: 2479: 1472:

published new guidelines urging companies to report all findings and limit the financial involvement in drug companies by researchers. The

1396:

will supervise noninterventional studies (observational studies or those using already collected data). In the US, this body is called the

5900: 1248:

Clinical trials that do not involve a new drug usually have a much shorter duration. (Exceptions are epidemiological studies, such as the

10504: 3684: 3127: 2963: 2367: 10128: 8769: 6320: 3274: 2840: 2666:

Metwally, Mostafa; Raybould, Grace; Cheong, Ying C; Horne, Andrew W (29 January 2020). Cochrane Gynaecology and Fertility Group (ed.).

1867:

payments to local researchers and their staff for their time and effort in recruiting test subjects and collecting data for the sponsor

1277:

can also be hired to coordinate with the CRO to ensure rapid IRB/IEC approval and faster site initiation and patient recruitment. Phase

994:

Placebo-controlled: The use of a placebo (fake treatment) allows the researchers to isolate the effect of the study treatment from the

6148: 5601: 5569: 5537: 1521:

in the US. Researchers may be restricted from contributing to the trial design, accessing the raw data, and interpreting the results.

7114: 3996: 732:

trials are conducted to assess the prediction accuracy of genetic disorders making a person more or less likely to develop a disease.

544: 382: 4403: 2021:. There also is software that allows clinicians to find trial options for an individual patient based on data such as genomic data. 9902: 6875: 6871: 4780: 1426:

The notion of informed consent of participating human subjects exists in many countries but its precise definition may still vary.

1091: 5401: 3969: 1332:

are used in a majority of clinical trials to collect case report data from sites, manage its quality and prepare it for analysis.

10341: 7937: 6921: 6879: 6867: 1269:

II–IV the CRO recruits participating researchers, trains them, provides them with supplies, coordinates study administration and

1140:

autonomously provide informed consent, but depending on their age and other factors, may be required to provide informed assent.

7721: 5538:"Guidance for Industry and Investigators Safety Reporting Requirements for INDs and BA/BE Studies Small Entity Compliance Guide" 1954:

or participant recruitment plays a significant role in the activities and responsibilities of sites conducting clinical trials.

7550: 6576: 4111: 3623:"Defining Feasibility and Pilot Studies in Preparation for Randomised Controlled Trials: Development of a Conceptual Framework" 1468:

In response to specific cases in which unfavorable data from pharmaceutical company-sponsored research were not published, the

1245:), the study may be done during a limited part of the year (such as spring for pollen allergies), when the drug can be tested. 6283: 5329: 1209:

For chronic conditions such as cancer, it takes months, if not years, to see if a cancer treatment has an effect on a patient.

515:

in the 1920s as an accurate methodology for the proper design of experiments. Among his major ideas include the importance of

8408: 8336: 3428: 3053: 3026: 2881: 2834: 6041:"Racial/Ethnic and Sex Representation in US-Based Clinical Trials of Hearing Loss Management in Adults: A Systematic Review" 342:

to provide an accurate comparison for the demonstration of the intervention's efficacy was generally lacking. For instance,

54:

designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel

8764: 8464: 7942: 7042: 6958: 5455: 4332: 3832: 385:

attracted much attention in Europe; out of 1900 men, 1400 had died, most of them allegedly from having contracted scurvy.

193:

While most clinical trials test one alternative to the novel intervention, some expand to three or four and may include a

9368: 8516: 7974: 7726: 7652: 7505: 6823: 6538:

The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use

5431: 1576: 1342: 972:

A randomized controlled trial can provide compelling evidence that the study treatment causes an effect on human health.

17: 7332: 6793: 4871: 8384: 7691: 7324: 5094: 3769: 3747: 2014: 189:

Evaluation of the study drug or device relative to two or more already approved/common interventions for that condition

4803:"Information Sheet Guidance For IRBs, Clinical Investigators, and Sponsors: FDA Inspections of Clinical Investigators" 3216:

Pottegård, Anton; Haastrup, Maija Bruun; Stage, Tore Bjerregaard; Hansen, Morten Rix; et al. (16 December 2014).

1864:

payments to the contract research organization, the site management organization (if used) and any outside consultants

648:, the investigators observe the subjects and measure their outcomes. The researchers do not actively manage the study. 242:

Similarly to drugs, manufacturers of medical devices in the United States are required to conduct clinical trials for

10151: 10043: 7796: 7152: 6569: 5277: 4516: 3863: 3533:"Randomized clinical trials and observational studies: guidelines for assessing respective strengths and limitations" 3496: 3114: 2993: 2946: 2925: 2905: 1812:

International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use

1716: 1401: 629: 1698: 659:

Trials are classified by their purpose. After approval for human research is granted to the trial sponsor, the U.S.

173:

Examples of clinical trial goals include assessing the safety and relative effectiveness of a medication or device:

82:

of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted.

10756: 10329: 10203: 8425: 8363: 7333: 7080: 5851:"What influences recruitment to randomised controlled trials? A review of trials funded by two UK funding agencies" 5684: 1767:

the investigator updates the IRB on the progress of the study and any new safety information related to the study.

1320: 1095: 740:

trials have the goal of identifying the general causes, patterns or control of diseases in large numbers of people.

78:

approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the

6039:

Pittman, Corinne A.; Roura, Raúl; Price, Carrie; Lin, Frank R.; Marrone, Nicole; Nieman, Carrie L. (1 July 2021).

1429:

Informed consent is clearly a 'necessary' condition for ethical conduct but does not 'ensure' ethical conduct. In

262:

device. An example of the latter are clinical trials on mechanical devices used in the management of adult female

85:

Depending on product type and development stage, investigators initially enroll volunteers or patients into small

10387: 10048: 9793: 9164: 8754: 7984: 7952: 7947: 7776: 4542: 2242: 2139: 1690: 1341:

were often paper based in the past, measurements are increasingly being collected using web portals or hand-held

1329: 508: 139: 6887: 10788: 10783: 10438: 9650: 9457: 9346: 9304: 8042: 7647: 6925: 6647: 3298:"EU Compassionate Use Programmes (CUPs): Regulatory Framework and Points to Consider before CUP Implementation" 1694: 1514: 1262: 1075: 299: 186:

Evaluation for improved efficacy in treating a condition as compared to the standard therapy for that condition

167: 118: 9378: 5210:"NINDS Guidelines for Monitoring in Clinical Trials | National Institute of Neurological Disorders and Stroke" 4802: 4075:

Weiss SC, Rowell R, Krochmal L (2008). "Impact of seasonality on conducting clinical studies in dermatology".

2290: 39: 10681: 9640: 8543: 7840: 7545: 7107: 7073: 6758: 6014:"Nearly Half of Black Patients With Metastatic Breast Cancer Report Not Being Informed About Clinical Trials" 5293: 4582:"Who pays for the pizza? Redefining the relationships between doctors and drug companies. 2: Disentanglement" 4032:

American Society of Clinical Oncology Educational Book. American Society of Clinical Oncology. Annual Meeting

1901: 1626: 1580: 1489: 1372:

A clinical trial produces data that could reveal quantitative differences between two or more interventions;

451: 378: 4328:

Small Clinical Trials Issues and Challenges; In: Statistical Approaches to Analysis of Small Clinical Trials

4187: 10232: 10181: 10166: 10156: 10025: 9897: 9864: 9690: 9645: 9475: 7052: 5325: 4810: 2018: 1776: 1605: 1539: 1274: 877: 870: 762: 716: 660: 259: 6040: 10798: 10744: 10576: 10377: 10301: 9602: 9356: 9025: 8489: 7016: 6988: 6917: 6671: 1390: 1367: 1234: 1175: 954: 779: 702:

trials are conducted to find better tests or procedures for diagnosing a particular disease or condition.

481: 200:

Except for small, single-location trials, the design and objectives are specified in a document called a

4325:

Evans Jr., CH; Ildstad, ST, eds. (2001). "Statistical Approaches to Analysis of Small Clinical Trials".

3744:"Foundation Medicine Joins Coalition Aiming to Shake Up Cancer Drug Trials | MIT Technology Review" 2898:

Scurvy: How a Surgeon, a Mariner, and a Gentleman Solved the Greatest Medical Mystery of the Age of Sail

10793: 10461: 10433: 10428: 10176: 9935: 9841: 9821: 9729: 9440: 9258: 8741: 8613: 7962: 7399: 7382: 7066: 6742: 1756: 1609: 1397: 1333: 1287: 1169: 1067: 987:

Randomized: Each study subject is randomly assigned to receive either the study treatment or a placebo.

390: 75: 4226: 2348: 720:

trials (supportive care trials) evaluate how to improve comfort and quality of care for people with a

10193: 9961: 9682: 9607: 9536: 9465: 9385: 9373: 9243: 9231: 9224: 8932: 8653: 8012: 6861: 2491: 2109: 1630: 1542:

authored a report identifying seven ethical and scientific considerations. These considerations are:

938: 797: 343: 251: 63: 31: 2329: 1416:, the state has prioritized the individuals who can serve as the legally authorized representative. 547:

officially recognized the importance of clinical trials from the 1930s. The council established the

10778: 10676: 10443: 10306: 9991: 9956: 9920: 9705: 9147: 9056: 9015: 8927: 8618: 8457: 7967: 7932: 7927: 7922: 7229: 7100: 6799: 6747: 6627: 5958:"Racial and Ethnic Disparities in Research Studies: The Challenge of Creating More Diverse Cohorts" 2767:"Public Information Pack (PIP): How to get involved in NHS, public health and social care research" 2054: 1679: 1386: 1338: 536: 520: 219: 6095: 5240:"Data and Safety Monitoring Board Training Manual for Investigator-Initiated Studies – Tufts CTSI" 282:. However, when clinical trials are unethical or logistically impossible in the surgical setting, 10803: 10585: 10198: 10138: 10075: 9713: 9697: 9435: 9297: 9287: 9137: 9051: 8413: 8346: 8327: 8123: 8095: 8057: 8052: 8032: 7555: 6845: 6715: 6693: 6662: 6637: 6620: 4028:"The Role of Clinical Trial Participation in Cancer Research: Barriers, Evidence, and Strategies" 3805: 2535:"Outcomes following endovascular vs open repair of abdominal aortic aneurysm: a randomized trial" 2165: 2114: 2062: 1934: 1683: 1650:

The sponsor and the local site investigators are jointly responsible for writing a site-specific

1518: 1325: 1249: 1182: 1121: 1059: 1053: 946: 757: 524: 457: 227: 201: 110: 4841: 3196: 1885:

the expense of treating a test subject who develops a medical condition caused by the study drug

468:, made substantial contributions to the process of clinical trials, where "he separated chronic 10623: 10553: 10346: 10283: 10038: 9925: 8922: 8819: 8726: 8605: 8504: 8394: 8323: 7317: 7285: 7188: 7183: 7137: 6996: 6833: 6754: 5904: 2869: 2005: 1497: 1316: 560: 527:, measurements should be repeated and experiments replicated to identify sources of variation; 473: 51: 5002:"Treatment Guidelines in Bipolar Disorders and the Importance of Proper Clinical Trial Design" 3043: 121:

or a central laboratory. Only 10 percent of all drugs started in human clinical trials become

10648: 10590: 10533: 10359: 10252: 10161: 9887: 9771: 9630: 9622: 9512: 9504: 9319: 9215: 9193: 9152: 9117: 9084: 9030: 9005: 8960: 8899: 8859: 8661: 8484: 8389: 8223: 8218: 7669: 7615: 7525: 7142: 6837: 6724: 6632: 6596: 4302: 3131: 2959: 2873: 2863: 2792:"Briefing notes for researchers - public involvement in NHS, health and social care research" 1793: 1350: 950: 920: 687: 607: 602:

in 1950, which compared lung cancer patients with matched control and also began a sustained

528: 516: 401: 98: 94: 6561: 6316: 4753: 4736: 3680: 3270: 3016: 2824: 10571: 10146: 10095: 10071: 10033: 9951: 9930: 9882: 9761: 9739: 9708: 9617: 9494: 9445: 9363: 9336: 9292: 9248: 9010: 8786: 8666: 8272: 8213: 8004: 7642: 7520: 7471: 7438: 7372: 6803: 6152: 5186: 5169: 4448: 3634: 3621:

Eldridge SM, Lancaster GA, Campbell MJ, Thabane L, Hopewell S, Coleman CL, Bond CM (2016).

1785: 1346: 1041: 708:

trials test experimental drugs, new combinations of drugs, or new approaches to surgery or

575: 532: 496: 263: 231: 2313:

Of the drugs started in clinical trials on humans, only 10 percent secure F.D.A. approval.

1930: 808:

process will normally proceed through phases I–IV over many years, frequently involving a

8: 10718: 10643: 10566: 10247: 10011: 10004: 9966: 9874: 9854: 9826: 9559: 9425: 9420: 9410: 9402: 9220: 9181: 9071: 9061: 8970: 8749: 8705: 8623: 8548: 8450: 8195: 8161: 8047: 7870: 7813: 7808: 7754: 7585: 7453: 7425: 7377: 7178: 7168: 6710: 6642: 5759:"More than the money: A review of the literature examining healthy volunteer motivations" 5478:"Management of Safety Information from Clinical Trials: Report of CIOMS Working Group VI" 4410: 2087: 1951: 645: 59: 7865: 7605: 6549: 6395:"Consensus recommendations for improving the cancer clinical trial matching environment" 4776: 4452: 3856:

Protection of Human Research Subjects: A Practical Guide to Federal Laws and Regulations

3638: 3197:

ISCR releases Guide for clinical trial participants on International Clinical Trials Day

586:, among others. He became famous for a landmark study carried out in collaboration with 10732: 10543: 10397: 10293: 10242: 10118: 10015: 9999: 9976: 9753: 9487: 9470: 9430: 9341: 9236: 9198: 9169: 9129: 9089: 9035: 8952: 8638: 8633: 8228: 8062: 7803: 7764: 7749: 7625: 7610: 7595: 7515: 7433: 7147: 6963: 6913: 6728: 6657: 6615: 6511: 6486: 6462: 6435: 6370: 6343: 6262: 6211: 6176: 6076: 5990: 5957: 5877: 5850: 5827: 5783: 5758: 5734: 5707: 5658: 5409: 5378: 5351: 5034: 5001: 4928: 4895: 4717: 4606: 4581: 4508: 4380: 4355: 4285: 4252: 4088: 4052: 4027: 3973: 3946: 3929: 3905: 3880: 3657: 3622: 3603: 3475: 3319: 3244: 3217: 3178: 2743: 2716: 2692: 2667: 2648: 2600: 2575: 2295: 2286: 2066: 2010: 1958: 1485: 966: 640:

Clinical trials are classified by the research objective created by the investigators.

599: 283: 255: 243: 218:

The most common clinical trials evaluate new pharmaceutical products, medical devices,

79: 67: 3462: 3445: 1879:

expense incurred by the local researchers, such as pharmacy fees, IRB fees and postage

10727: 10638: 10608: 10600: 10420: 10411: 10336: 10267: 10123: 10108: 10083: 9971: 9912: 9778: 9766: 9392: 9309: 9253: 9176: 9020: 8942: 8721: 8595: 8351: 8318: 8151: 7992: 7882: 7771: 7632: 7457: 7420: 7310: 7213: 7037: 7001: 6968: 6893: 6815: 6592: 6516: 6467: 6416: 6375: 6254: 6216: 6198: 6080: 6068: 6060: 5995: 5977: 5882: 5788: 5739: 5708:"The Internet and clinical trials: background, online resources, examples and issues" 5650: 5383: 5273: 5191: 5147: 5139: 5086: 5078: 5039: 5021: 4982: 4974: 4933: 4915: 4863: 4858: 4758: 4709: 4611: 4550: 4466: 4385: 4290: 4272: 4092: 4057: 3951: 3910: 3859: 3662: 3595: 3554: 3467: 3424: 3249: 3170: 3110: 3092: 3049: 3022: 2942: 2921: 2901: 2877: 2830: 2748: 2697: 2640: 2605: 2556: 2416: 2224: 1731: 1430: 1150: 709: 671: 603: 461: 440:

demonstrated the importance of a control group for the correct identification of the

295: 223: 212: 90: 8297: 5831: 5662: 5319: 4512: 4219:"Electronic Patient Reported Outcomes (ePRO) – Changing the Face of Clinical Trials" 4118: 3607: 3479: 3323: 3182: 2652: 1513:

strengthened editorial restrictions to counter the effect. The editorial noted that

306:

that is clear to the wider society and the specific groups it is most relevant for.

211:

and rigorously monitor and assess outcomes, it can be seen as an application of the

10663: 10618: 10382: 10369: 10262: 10237: 10171: 10103: 9981: 9589: 9482: 9415: 9328: 9275: 9094: 8965: 8759: 8643: 8558: 8525: 8277: 8262: 8118: 7979: 7892: 7254: 7198: 6811: 6732: 6686: 6681: 6506: 6498: 6457: 6447: 6406: 6365: 6355: 6266: 6246: 6206: 6188: 6052: 5985: 5969: 5872: 5862: 5819: 5778: 5770: 5729: 5719: 5640: 5373: 5363: 5181: 5129: 5070: 5029: 5013: 4964: 4923: 4907: 4853: 4748: 4721: 4701: 4601: 4593: 4500: 4456: 4375: 4367: 4280: 4264: 4084: 4047: 4039: 3941: 3900: 3892: 3652: 3642: 3585: 3544: 3457: 3309: 3239: 3229: 3162: 3082: 2738: 2728: 2717:"Study design in evidence-based surgery: What is the role of case-control studies?" 2687: 2683: 2679: 2632: 2595: 2591: 2587: 2546: 2408: 2214: 2210: 2206: 2058: 1760: 1651: 1634: 1408: 1133: 1104: 976: 839: 835: 805: 564: 504: 359: 247: 86: 7818: 2508:"Medical Devices, Premarket Clinical Studies for Investigational Device Exemption" 2033:

Eli Lilly pharmaceutical company recruiting participants at the Indiana State Fair

2029: 10580: 10324: 10186: 10113: 9788: 9662: 9635: 9612: 9581: 9208: 9203: 9157: 8887: 8538: 8282: 8080: 7887: 7845: 7731: 7711: 7681: 7664: 7590: 7580: 7510: 7449: 7445: 7394: 7249: 7203: 7123: 7006: 6829: 6784: 6552:; a concentrated source for bibliographic reports of randomized controlled trials 6502: 6250: 5368: 5059:"Severity of symptoms in mania-clinical guidelines and study design implications" 4911: 4705: 3840: 3647: 3590: 3573: 3418: 3203: 2636: 2374: 2355: 2336: 2099: 1947: 1850:

The expenses incurred by a pharmaceutical company in administering a Phase III or

1655:

subject having the right not to participate or to end participation at any time.

1434: 1270: 1126: 1036: 747: 721: 578:, who had been involved in the streptomycin trials. From the 1920s, Hill applied 102: 10070: 4326: 3881:"Statistics in Brief: Statistical Power: What Is It and When Should It Be Used?" 3273:. National Library of Medicine, US National Institutes of Health. 1 March 2019. 10524: 8987: 8917: 8563: 8146: 8037: 7997: 7877: 7698: 7637: 7259: 7234: 7032: 6953: 6905: 6698: 6452: 6360: 6193: 3549: 3532: 3420:

The Cure in the Code: How 20th Century Law Is Undermining 21st Century Medicine

2487: 2104: 1897: 1802:

investigator makes a significant contribution to the demonstration of safety."

1525: 1438: 1030: 1017: 995: 446: 441: 422: 303: 71: 6056: 5774: 5438: 5134: 5117: 4969: 4952: 4597: 4371: 4184:"BIO to Use ViS Analytics to Streamline Pediatric Clinical Research - WSJ.com" 3896: 2366:

Merck Manual. Last full review/revision October 2013 by Daniel A. Hussar, PhD

1132:

Clinical trials recruit study subjects to sign a document representing their "

519:—the random assignment of individuals to different groups for the experiment; 10772: 10686: 10653: 10516: 10477: 10288: 10257: 9721: 9675: 9280: 8982: 8809: 8573: 8568: 8302: 8287: 8257: 8252: 8107: 7860: 7855: 7759: 7404: 7280: 7193: 7173: 7011: 6978: 6973: 6202: 6064: 5981: 5645: 5628: 5143: 5082: 5025: 4978: 4919: 4554: 4504: 4276: 3780: 3729: 2483: 2412: 1913:

investigator to pay the research staff during times between clinical trials.

1643: 1639: 1565:

Post-trial access to tested therapies that had been withheld during the trial

1502: 1457: 1087: 679: 611: 437: 436:

After 1750 the discipline began to take its modern shape. The English doctor

414: 355: 339: 331: 323: 122: 114: 7659: 4268: 3166: 3087: 3070: 1896:

for clinical trials conducted on drugs being developed for the treatment of

230:, or other interventions. Clinical trials may be required before a national 10628: 10561: 10538: 10453: 9783: 9079: 8977: 8912: 8854: 8839: 8776: 8731: 8379: 8022: 7917: 7850: 7791: 7786: 7466: 7357: 7337: 7291: 7264: 6853: 6737: 6520: 6471: 6420: 6379: 6258: 6220: 6072: 5999: 5886: 5792: 5743: 5677:"Tax Credit for Testing Expenses for Drugs for Rare Diseases or Conditions" 5654: 5627:

Sertkaya, Aylin; Wong, Hui-Hsing; Jessup, Amber; Beleche, Trinidad (2016).

5387: 5195: 5151: 5090: 5058: 5043: 4986: 4937: 4867: 4762: 4713: 4615: 4470: 4389: 4294: 4096: 4061: 3955: 3914: 3666: 3599: 3558: 3471: 3392:"Health: Scientists Look to Improve Cost and Time of Drug Trials - WSJ.com" 3253: 3174: 2752: 2701: 2644: 2609: 2560: 2551: 2534: 2420: 2228: 1938: 1792:), about which the FDA may require disclosure of financial interest of the 1242: 1230: 962: 958: 736: 619: 587: 583: 556: 477: 430: 394: 386: 327: 5867: 5017: 3096: 2985: 2733: 1193: 450:. Further work in that direction was carried out by the eminent physician 10671: 10633: 10316: 10217: 10079: 9892: 9859: 9351: 9268: 9263: 8907: 8864: 8844: 8824: 8814: 8583: 8166: 8156: 8017: 7823: 7706: 7674: 7600: 7462: 7353: 7345: 7208: 7047: 6901: 6774: 6764: 5973: 5676: 5629:"Key cost drivers of pharmaceutical clinical trials in the United States" 4485: 1817: 1473: 1229:

For clinical trials involving potential for seasonal influences (such as

975:

Some Phase II and most Phase III drug trials are designed as randomized,

858: 595: 347: 338:

Although early medical experimentation was performed often, the use of a

279: 250:

is the Open versus Endovascular Repair (OVER trial) for the treatment of

163: 5724: 4043: 365:

The first proper clinical trial was conducted by the Scottish physician

9517: 8997: 8697: 8628: 8578: 8553: 8473: 8292: 8267: 7957: 7907: 7239: 6849: 6841: 6807: 6769: 6676: 6411: 6394: 5823: 5602:"Evidence Synthesis and Meta-Analysis: Report of CIOMS Working Group X" 3970:"Frequently Asked Questions | University of Arizona Cancer Center" 3314: 3297: 2219: 2083: 1893: 1449: 1413: 1373: 696:

trials test for ways to identify certain diseases or health conditions.

579: 492: 366: 208: 6544:

ClinicalTrials.gov, a worldwide database of registered clinical trials

5074: 4145:"Implementing QbD in Your Clinical Trial? 4 Questions To Answer First" 3234: 1007:

submitted for regulatory review that would determine market approval.

663:(FDA) organizes and monitors the results of trials according to type: 9670: 9522: 9142: 8937: 8849: 8834: 8829: 8794: 8341: 7912: 7780: 7349: 6909: 6897: 5321:

Guidance for Industry: Financial Disclosure by Clinical Investigators

5272:. International Journal of Statistics and Medical Informatics. 2019. 1238: 469: 374: 6436:"Decentralized clinical trials (DCTs): A few ethical considerations" 4461: 4436: 3930:"FDA approval for use of medications in pregnancy: an uphill battle" 1668: 610:

over a period of several years. His certificate for election to the

9186: 8804: 8681: 8676: 8671: 8183: 8176: 8171: 8141: 7897: 7833: 7828: 6943: 6177:"MatchMiner: an open-source platform for cancer precision medicine" 2622: 1587: 728: 351: 7092: 5570:"Safety Assessment for IND Safety Reporting Guidance for Industry" 3574:"Clinical Research Methodology 2: Observational Clinical Research" 2532: 608:

studying the smoking habits and health of more than 30,000 doctors

499:

was a pivotal figure in the modern development of clinical trials.

319: 10691: 10392: 7902: 7341: 6948: 6096:"How to stop a lack of diversity undermining clinical trial data" 5463: 4662:"Rise in Scientific Journal Retractions Prompts Calls for Reform" 4630:"Hogan & Hartson Update on Pharmaceutical Trial Registration" 3728:

This article incorporates text from this source, which is in the

1870:

the cost of study materials and the charges incurred to ship them

1197:

Timeline of various approval tracks and research phases in the US

980: 874: 683: 675: 591: 568: 418: 410: 275: 194: 55: 6126: 4112:"Seasonality: The Clinical Trial Manager's Logistical Challenge" 3620: 1861:

staff salaries for the designers and administrators of the trial

1463: 574:

The methodology of clinical trials was further developed by Sir

397:

from the 17th century, but their use did not become widespread.

10613: 9594: 9568: 9548: 8799: 8590: 8205: 8190: 7476: 6556:

ClinicalTrials.eu, European Clinical Trials Information Network

6342:

Fountzilas E, Tsimberidou AM, Vo HH, Kurzrock R (August 2022).

6341: 5848: 5170:"Ethics of Conducting Clinical Research in an Outbreak Setting" 4839: 1968:

Measurement of blood pressure, heart rate, and body temperature

1789: 1612:, or for small or low-risk studies the principal investigator. 1157: 809: 465: 370: 6543: 5514:. Center for Drug Evaluation and Research. 29 September 2010. 4543:"When a Drug Study Abruptly Ends, Volunteers Are Left to Cope" 3707:"Master Protocols for Drug and Biological Product Development" 582:

to medicine, attending the lectures of renowned mathematician

480:. He also founded the Collective Investigation Record for the 421:, group four half a pint of seawater, group five received two 8442: 8200: 8085: 7686: 7620: 6591: 6319:. ClinicalTrials.gov, US National Library of Medicine. 2023. 3365:"Adaptive Clinical Trials for Overcoming Research Challenges" 1780: 606:

into the broader issue of smoking and health, which involved

426: 406: 151: 50:

are prospective biomedical or behavioral research studies on

6555: 6284:"What to Know About Cancer Clinical Trial Matching Programs" 3997:"Janssen Uses Geofencing To Monitor Clinical Trial Patients" 3215: 1925: 632:

are often contrived, and have been the subject of derision.

507:

still play a role in clinical trials. While working for the

8533: 7495: 4257:

Journal of Experimental Stroke & Translational Medicine

2665: 1484:

III clinical trials to be registered by the sponsor on the

1441:), and then quantified methods may play an important role. 625:

International clinical trials day is celebrated on 20 May.

3014: 6173: 5626: 5352:"Clinical trials have gone global: is this a good thing?" 3339:"CROs Slowly Shifting to Adaptive Clinical Trial Designs" 3015:

Green S, Crowley J, Benedetti J, Smith A (30 July 2002).

2265:"How long a new drug takes to go through clinical trials" 2243:"The Drug Development Process. Step 3: Clinical Research" 1965:

Measurement of the electrical activity of the heart (ECG)

444:

in his celebrated study of the ineffective remedy called

330:, a boy of eight, on 14 May 1796. Jenner failed to use a 6550:

Cochrane Central Register of Controlled Trials (CENTRAL)

6344:"Clinical trial design in the era of precision medicine" 5402:"India: Prime Destination for Unethical Clinical Trials" 2398: 1444:

Additional ethical concerns are present when conducting

1205:

Some reasons a clinical trial might last several years:

869:

Establishing the preliminary efficacy of the drug in a

30:"Clinical Trials" redirects here. For the journal, see 6537: 5270:

Designing and Conducting Clinical Trials – An overview

4486:"Emergency research and the interests of participants" 4038:(36). American Society of Clinical Oncology: 185–198. 3797: 2576:"Mechanical devices for urinary incontinence in women" 1858:

production of the drug(s) or device(s) being evaluated

1818:

Aggregation of safety data during clinical development

1108:, encourage investigators to publish their protocols. 138:

Some clinical trials involve healthy subjects with no

6236: 5296:. US Food and Drug Administration. 25 February 2016. 4892: 4690: 2196: 1750: 1608:, an externally appointed Medical Safety Monitor, an 10355:

Autoregressive conditional heteroskedasticity (ARCH)

6038: 5294:"For Patients: Informed Consent for Clinical Trials" 5122:

The International Journal of Neuropsychopharmacology

5006:

The International Journal of Neuropsychopharmacology

4957:

The International Journal of Neuropsychopharmacology

2941:, John Wiley & Songs, Inc., New Jersey. p. 393. 2454:"What are the different types of clinical research?" 2142:. US National Institutes of Health. 3 October 2022. 1470:

Pharmaceutical Research and Manufacturers of America

1407:

To be ethical, researchers must obtain the full and

1319:

use in the planning and conduct of clinical trials.

4356:"The Ethics of Withdrawal from Study Participation" 4074: 1600:the country where the drug or device will be sold. 429:, and the last group a spicy paste plus a drink of 43:

A clinical trial participant receives an injection.

9817: 6094: 4025: 3446:"Phase 0 trials: a platform for drug development?" 2818: 2816: 2814: 2812: 2510:. US Food and Drug Administration. 17 March 2017. 2140:"NIH Clinical Research Trials and You: The Basics" 1029:(multiple medical products for a single disease), 535:—efficient at evaluating the effects and possible 511:in the field of agriculture, Fisher developed his 8358:Cedillo v. Secretary of Health and Human Services 5808:"Achieving Ethnic Diversity in Trial Recruitment" 5805: 5543:. Food and Drug Administration =. December 2012. 2668:"Surgical treatment of fibroids for subfertility" 2245:. US Food and Drug Administration. 4 January 2018 289: 158:other locations are recruited to join the study. 10770: 5705: 5118:"Credibility of industry-funded clinical trials" 4953:"Credibility of industry-funded clinical trials" 4324: 4253:"Common statistical concerns in clinical trials" 3927: 3008: 2865:The Harvard Medical School guide to men's health 2616: 1889:These expenses are incurred over several years. 409:daily, group two twenty-five drops of elixir of 9903:Multivariate adaptive regression splines (MARS) 6540:, a guideline for regulation of clinical trials 5903:. Boston, MA: CenterWatch. 2016. Archived from 5575:. Food and Drug Administration. December 2015. 5349: 2822: 2809: 2796:National Institute for Health and Care Research 2771:National Institute for Health and Care Research 2573: 6278: 6276: 5757:Stunkel, Leanne; Grady, Christine (May 2011). 5167: 4353: 4026:Unger, JM; Cook, E; Tai, E; Bleyer, A (2016). 2939:Scientific American Inventions and Discoveries 2826:Clinical trials: design, conduct, and analysis 1882:any payments to subjects enrolled in the trial 1839:III trials from $ 11 million to $ 53 million. 1570: 1532: 1517:had, by 2000, received 60% of the grants from 1125:Example of informed consent document from the 8458: 7318: 7108: 6577: 5168:Edwards, Kathryn M.; Kochhar, Sonali (2020). 4307:: CS1 maint: DOI inactive as of March 2024 ( 2960:"James Lind: A Treatise of the Scurvy (1754)" 2013:to locate trials using a registry run by the 1892:In the US, sponsors may receive a 50 percent 1854:IV clinical trial may include, among others: 1559:Concern for participant welfare and interests 1464:Conflicts of interest and unfavorable studies 1102:also follow ICH guidelines. Journals such as 5927:"Diversity and Inclusion in Clinical Trials" 5756: 4842:"Sponsorship, authorship and accountability" 4777:"Development & Approval Process (Drugs)" 4186:. Online.wsj.com. 7 May 2013. Archived from 4003:. Pennsylvania, United States: VertMarkets. 3571: 3068: 2714: 2448: 2446: 2444: 2442: 2440: 2438: 2436: 2434: 2432: 2430: 2134: 2132: 2130: 1642:. The sponsor is responsible for collecting 1452:), and in emergency or epidemic situations. 1315:The last decade has seen a proliferation of 6273: 6045:JAMA Otolaryngology–Head & Neck Surgery 5799: 4573: 3018:Clinical Trials in Oncology, Second Edition 2829:. Oxford University Press, USA. p. 3. 2580:The Cochrane Database of Systematic Reviews 2574:Lipp A, Shaw C, Glavind K (December 2014). 1900:. National health agencies, such as the US 1697:. Unsourced material may be challenged and 1658: 1476:signed into law a bill which requires Phase 93:, in one country or in multiple countries. 8503: 8465: 8451: 7325: 7311: 7115: 7101: 6584: 6570: 6484: 5163: 5161: 4117:. Pharm-Olam International. Archived from 3885:Clinical Orthopaedics and Related Research 3443: 2478:The regulatory authority in the US is the 2235: 1876:one or more investigator training meetings 1047: 9116: 6510: 6461: 6451: 6410: 6369: 6359: 6210: 6192: 5989: 5876: 5866: 5782: 5733: 5723: 5706:Paul J, Seib R, Prescott T (March 2005). 5699: 5644: 5377: 5367: 5185: 5133: 5033: 4968: 4927: 4857: 4752: 4734: 4605: 4483: 4460: 4379: 4284: 4051: 3945: 3904: 3656: 3646: 3589: 3548: 3526: 3524: 3522: 3461: 3410: 3313: 3243: 3233: 3086: 2742: 2732: 2691: 2599: 2550: 2456:. US Food and Drug Administration. 2019. 2427: 2218: 2127: 1926:Participant recruitment and participation 1717:Learn how and when to remove this message 1345:(or eDiary) devices, sometimes wireless. 1310: 1084:International Conference on Harmonisation 1010: 891:Final confirmation of safety and efficacy 346:, who campaigned for the introduction of 6876:Preventable fraction among the unexposed 6872:Attributable fraction for the population 6232: 6230: 4579: 4246: 4244: 4142: 3858:. Boston, MA: Springer US. p. 151. 3614: 3497:"Phase IIa and Phase IIb clinical trial" 3357: 3265: 3263: 3152: 3048:. John Wiley & Sons. pp. 118–. 2715:Cao AM, Cox MR, Eslick GD (March 2016). 2472: 2257: 2028: 1929: 1192: 1120: 924: 783: 491: 318: 38: 6880:Preventable fraction for the population 6868:Attributable fraction among the exposed 6433: 6311: 6309: 5158: 4754:10.7326/0003-4819-149-4-200808190-00012 4437:"Ethical dilemma for Ebola drug trials" 4354:Gordon, E. J.; Prohaska, T. R. (2006). 3853: 3827: 3825: 3823: 3565: 3383: 3367:. News-medical.net. 17 September 2013. 3336: 3035: 2672:Cochrane Database of Systematic Reviews 2285: 2076: 269: 14: 10771: 10429:Kaplan–Meier estimator (product limit) 6392: 6335: 6294:from the original on 28 September 2023 5955: 5187:10.1146/annurev-virology-013120-013123 4728: 4434: 4320: 4318: 3994: 3934:Reviews in Obstetrics & Gynecology 3746:. Technologyreview.com. Archived from 3530: 3519: 3295: 2496:Ministry of Health, Labour and Welfare 1770: 800:video on the phases of clinical trials 234:approves marketing of the innovation. 215:, specifically the experimental step. 27:Phase of clinical research in medicine 10502: 10069: 9816: 9115: 8885: 8502: 8446: 7306: 7096: 6565: 6323:from the original on 26 December 2023 6227: 6149:"Medical Information on the Internet" 6127:"Parkinson's Disease Clinical Trials" 6107:from the original on 10 December 2022 5806:Liu JJ, Davidson E, Sheikh A (2011). 5115: 5056: 4999: 4950: 4779:. U.S. Food and Drug Administration. 4250: 4241: 4109: 3878: 3572:Sessler DI, Imrey PB (October 2015). 3491: 3489: 3416: 3390:Wang, Shirley S. (30 December 2013). 3260: 2861: 2267:. Cancer Research UK. 1 February 2022 2171:. Bill and Melinda Gates Foundation. 941:video on clinical trial randomization 393:, had recommended the consumption of 389:, an English military surgeon of the 350:(then called variolation) to prevent 10739: 10439:Accelerated failure time (AFT) model 7043:Correlation does not imply causation 6959:Animal testing on non-human primates 6558:; Clinical Trials easily understood. 6491:JACC: Basic to Translational Science 6317:"How to Search for Clinical Studies" 6306: 5712:Journal of Medical Internet Research 5550:from the original on 16 January 2019 4694:Current Medical Research and Opinion 4540: 4155:from the original on 27 January 2020 4143:Marshall, Megan (19 December 2019). 4007:from the original on 27 January 2020 3820: 3681:"Active Control / Active Comparator" 3389: 3125: 3062: 2996:from the original on 5 February 2023 2900:. New York, NY: St. Martin's Press. 2526: 2514:from the original on 1 November 2017 2330:FDA's Drug Review Process: Continued 2328:FDA Page last updated 25 April 2014 2303:from the original on 5 December 2022 2178:from the original on 12 January 2017 2158: 1695:adding citations to reliable sources 1662: 1562:A balance towards benefit over risks 1143: 957:. Types of observational studies in 400:Lind conducted the first systematic 237: 10751: 10034:Analysis of variance (ANOVA, anova) 8886: 7122: 6485:Van Norman, G. A. (27 April 2021). 6434:Petrini, Carlo (15 December 2022). 5901:"Volunteering for a Clinical Trial" 5893: 5608:from the original on 15 August 2019 5488:from the original on 15 August 2019 5448: 5000:Tohen, Mauricio (1 February 2017). 4315: 3371:from the original on 11 August 2020 3345:from the original on 27 August 2017 3195:Pharmabiz.com, 19 May 2014, Mumbai 3041: 2966:from the original on 1 October 2018 2784: 1577:pregnant women in clinical research 1353:. In 2011, the FDA approved a Phase 1185:provides guidelines on this issue. 1116: 24: 10129:Cochran–Mantel–Haenszel statistics 8755:Pearson product-moment correlation 8385:Eradication of infectious diseases 8142:Androvax (androstenedione albumin) 5937:from the original on 18 March 2023 5518:from the original on 23 April 2019 5456:"ICH Official web site : ICH" 4951:Tohen, Mauricio (September 2013). 4874:from the original on 15 April 2023 4335:from the original on 15 April 2023 4089:10.1016/j.clindermatol.2008.01.016 3972:. Azcc.arizona.edu. Archived from 3798:"ICH Official web site : ICH" 3537:JACC. Cardiovascular Interventions 3507:from the original on 9 August 2020 3486: 2843:from the original on 15 April 2023 2759: 2368:Overview of Over-the-Counter Drugs 2146:from the original on 22 April 2020 2015:U.S. National Institutes of Health 1995: 1751:Institutional review boards (IRBs) 1400:(IRB); in the EU, they are called 1380: 1324:about ongoing research. Web-based 1111: 1023: 362:were equally conceptually flawed. 133: 25: 10815: 7975:Respiratory syncytial virus (RSV) 6546:; US National Library of Medicine 6531: 6020:from the original on 7 April 2023 5962:Environmental Health Perspectives 5687:from the original on 6 April 2007 5300:from the original on 22 July 2017 5250:from the original on 7 April 2023 5097:from the original on 8 April 2023 4821:from the original on 11 June 2014 4783:from the original on 10 June 2018 4672:from the original on 18 June 2018 4561:from the original on 7 April 2023 4522:from the original on 9 April 2023 4331:. National Academies Press (US). 3928:Norwitz ER, Greenberg JA (2011). 3741: 3687:from the original on 8 April 2023 2460:from the original on 12 June 2019 1941:to participate in clinical trials 1321:Clinical trial management systems 1255: 1163: 1086:(ICH). Regulatory authorities in 513:Principles of experimental design 76:health authority/ethics committee 10750: 10738: 10726: 10713: 10712: 10503: 8364:Alternative vaccination schedule 7334:Artificial induction of immunity 6478: 6427: 6386: 6167: 6141: 6119: 6087: 6032: 6006: 5949: 5919: 5842: 5750: 5669: 5620: 5594: 5562: 5332:from the original on 11 May 2009 4735:Sox HC, Rennie D (August 2008). 3808:from the original on 25 May 2011 3723: 3394:. Online.wsj.com. Archived from 3277:from the original on 19 May 2019 2920:. New York, NY: The Free Press. 1907: 1667: 1586:During the early history of the 1505:are particularly controversial. 1330:clinical data management systems 545:British Medical Research Council 487: 417:), group three six spoonfuls of 10388:Least-squares spectral analysis 6487:"Decentralized Clinical Trials" 6239:Journal of Health Communication 5582:from the original on 4 May 2017 5530: 5500: 5470: 5432:"Pmda.go.jp 独立行政法人医薬品医療機器総合機構" 5424: 5394: 5343: 5312: 5286: 5262: 5232: 5202: 5109: 5050: 4993: 4944: 4886: 4833: 4795: 4769: 4737:"Seeding trials: just say "no"" 4684: 4654: 4622: 4534: 4477: 4428: 4396: 4347: 4211: 4202: 4176: 4167: 4136: 4103: 4068: 4019: 3995:Miseta, Ed (17 December 2019). 3988: 3962: 3921: 3872: 3847: 3790: 3762: 3735: 3699: 3673: 3437: 3330: 3289: 3209: 3189: 3146: 3119: 3103: 2978: 2952: 2931: 2910: 2890: 2855: 2823:Meinert CL, Tonascia S (1986). 2708: 2659: 2567: 2500: 2392: 2379: 1515:contract research organizations 914: 813:risks, benefits, or best uses. 509:Rothamsted experimental station 207:As a trial is designed to test 140:pre-existing medical conditions 9369:Mean-unbiased minimum-variance 8472: 8196:Ovandrotone albumin (Fecundin) 6926:Pre- and post-test probability 6648:Patient and public involvement 5350:Lang T, Siribaddana S (2012). 4635:. 3 March 2008. Archived from 3833:"Learn About Clinical Studies" 2684:10.1002/14651858.CD003857.pub4 2592:10.1002/14651858.CD001756.pub6 2389:, pp. 129–33. Alfred A. Knopf. 2360: 2349:Drug Discovery and Development 2341: 2322: 2279: 2211:10.1016/j.jhealeco.2016.01.012 2190: 1263:contract research organization 1261:are usually administered by a 1076:contract research organization 373:, now known to be caused by a 314: 300:patient and public involvement 290:Patient and public involvement 119:contract research organization 13: 1: 10682:Geographic information system 9898:Simultaneous equations models 7727:Group B streptococcal disease 7546:Vaccines for Children Program 4151:. Pennsylvania: VertMarkets. 3463:10.1016/S0140-6736(09)61309-X 3417:Huber PW (12 November 2013). 3069:O'Rourke MF (February 1992). 2291:"The Solution to Drug Prices" 2120: 1977:Weight and height measurement 1937:seeking patients and healthy 1902:National Institutes of Health 1581:Children in clinical research 1490:National Institutes of Health 1275:site management organizations 945:A fundamental distinction in 452:Sir William Gull, 1st Baronet 177:On a specific kind of patient 9865:Coefficient of determination 9476:Uniformly most powerful test 7053:Sex as a biological variable 6503:10.1016/j.jacbts.2021.01.011 6251:10.1080/10810730.2011.635774 6151:. Mlanet.org. Archived from 5763:Contemporary Clinical Trials 5681:Food and Drug Administration 5604:. CIOMS Publications. 2016. 5369:10.1371/journal.pmed.1001228 5326:Food and Drug Administration 4912:10.1016/j.mayocp.2012.02.009 4811:Food and Drug Administration 4706:10.1185/03007995.2011.573546 4541:Span, Paula (3 March 2020). 4484:Pattinson, Shaun D. (2012). 3648:10.1371/journal.pone.0150205 3591:10.1213/ANE.0000000000000861 3155:Journal of Medical Biography 2721:World Journal of Methodology 2637:10.1097/SLA.0b013e3181cf863d 2480:Food and Drug Administration 2019:National Library of Medicine 1842: 1826: 1761:Independent Ethics Committee 1540:National Academy of Medicine 1301: 955:randomized controlled trials 763:Bayesian experimental design 661:Food and Drug Administration 549:Therapeutic Trials Committee 260:endovascular aneurysm repair 7: 10434:Proportional hazards models 10378:Spectral density estimation 10360:Vector autoregression (VAR) 9794:Maximum posterior estimator 9026:Randomized controlled trial 7017:Intention-to-treat analysis 6989:Analysis of clinical trials 6918:Specificity and sensitivity 6672:Randomized controlled trial 4741:Annals of Internal Medicine 4435:Hayden EC (November 2014). 3501:www.musculardystrophyuk.org 3271:"What is a clinical study?" 2986:"About Clinical Trials Day" 2916:Rogers, Everett M. (1995). 2199:Journal of Health Economics 2093: 2041: 2024: 1916: 1571:Pregnant women and children 1533:During public health crisis 1446:clinical trials on children 1391:Clinical trials publication 1368:Analysis of clinical trials 1361: 1235:seasonal affective disorder 1188: 903:Safety studies during sales 780:Phases of clinical research 604:long-term prospective study 590:on the correlation between 482:British Medical Association 254:, which compared the older 128: 10: 10820: 10194:Multivariate distributions 8614:Average absolute deviation 6453:10.3389/fpubh.2022.1081150 6361:10.1186/s13073-022-01102-1 6194:10.1038/s41698-022-00312-5 4360:Accountability in Research 4271:(inactive 17 March 2024). 3854:Maloney, Dennis M (1984). 3550:10.1016/j.jcin.2008.01.008 3341:. Outsourcing-pharma.com. 3021:. CRC Press. pp. 1–. 2896:Brown, Stephen R. (2003). 1757:Institutional Review Board 1619: 1610:Independent Safety Officer 1574: 1398:Institutional Review Board 1384: 1365: 1334:Interactive voice response 1293: 1288:institutional review board 1170:Placebo-controlled studies 1167: 1051: 918: 777: 630:titling of clinical trials 391:British East India Company 309: 29: 10708: 10662: 10599: 10552: 10515: 10511: 10498: 10470: 10452: 10419: 10410: 10368: 10315: 10276: 10225: 10216: 10182:Structural equation model 10137: 10094: 10090: 10065: 10024: 9990: 9944: 9911: 9873: 9840: 9836: 9812: 9752: 9661: 9580: 9544: 9535: 9518:Score/Lagrange multiplier 9503: 9456: 9401: 9327: 9318: 9128: 9124: 9111: 9070: 9044: 8996: 8951: 8933:Sample size determination 8898: 8894: 8881: 8785: 8740: 8714: 8696: 8652: 8604: 8524: 8515: 8511: 8498: 8480: 8403: 8372: 8311: 8243: 8134: 8106: 8073: 7742: 7573: 7566: 7485: 7413: 7365: 7273: 7222: 7161: 7130: 7061: 7026:Interpretation of results 7025: 6987: 6936: 6886: 6860: 6822: 6792: 6783: 6759:Nested case–control study 6709: 6656: 6603: 6057:10.1001/jamaoto.2021.0550 5775:10.1016/j.cct.2010.12.003 5174:Annual Review of Virology 5135:10.1017/S1461145713000461 4970:10.1017/S1461145713000461 4598:10.1136/bmj.326.7400.1193 4493:Medical Law International 4372:10.1080/08989620600848645 3897:10.1007/s11999-010-1435-0 3879:Dorey, Frederick (2011). 3337:Brennan Z (5 June 2013). 3206:(Accessed on 20 May 2014) 3071:"Frederick Akbar Mahomed" 2937:Carlisle, Rodney (2004). 2862:Simon, Harvey B. (2002). 2492:European Medicines Agency 2110:Preregistration (science) 2055:Electronic health records 1729:The ethical principle of 1631:data monitoring committee 1606:Data and Safety Committee 1594: 939:National Cancer Institute 798:National Cancer Institute 773: 628:The acronyms used in the 460:(d. 1884), who worked at 344:Lady Mary Wortley Montagu 252:abdominal aortic aneurysm 32:Clinical Trials (journal) 10677:Environmental statistics 10199:Elliptical distributions 9992:Generalized linear model 9921:Simple linear regression 9691:Hodges–Lehmann estimator 9148:Probability distribution 9057:Stochastic approximation 8619:Coefficient of variation 7722:Clostridioides difficile 7153:Food safety organization 6628:Academic clinical trials 5956:Konkel, Lindsey (2015). 5646:10.1177/1740774515625964 5116:Tohen, Mauricio (2013). 5057:Tohen, Mauricio (2018). 4505:10.1177/0968533212465615 4404:"Assembly Bill No. 2328" 4251:Evans, Scott R. (2010). 3578:Anesthesia and Analgesia 3444:The Lancet (July 2009). 3045:Clinical Trials Handbook 2918:Diffusion of Innovations 2413:10.1001/jama.297.11.1233 1935:Newspaper advertisements 1659:Local site investigators 1519:pharmaceutical companies 1488:website compiled by the 1387:Clinical research ethics 1339:patient-reported outcome 758:Adaptive clinical trials 635: 10337:Cross-correlation (XCF) 9945:Non-standard predictors 9379:Lehmann–Scheffé theorem 9052:Adaptive clinical trial 7985:Tick-borne encephalitis 6846:Relative risk reduction 6694:Adaptive clinical trial 6638:Evidence-based medicine 6621:Adaptive clinical trial 4900:Mayo Clinic Proceedings 4586:British Medical Journal 4269:10.6030/1939-067x-3.1.1 3770:"ICH Official web site" 3531:Hannan EL (June 2008). 3167:10.1258/jmb.2010.010019 3088:10.1161/01.HYP.19.2.212 3042:Gad SC (17 June 2009). 2373:4 February 2015 at the 2115:Marketing authorisation 2063:artificial intelligence 1747:relating to the study. 1326:electronic data capture 1183:Declaration of Helsinki 1068:investigator's brochure 1060:clinical trial protocol 1054:Clinical trial protocol 1048:Clinical trial protocol 947:evidence-based practice 458:Frederick Akbar Mahomed 284:case-controlled studies 258:technique to the newer 228:psychological therapies 202:clinical trial protocol 10733:Mathematics portal 10554:Engineering statistics 10462:Nelson–Aalen estimator 10039:Analysis of covariance 9926:Ordinary least squares 9850:Pearson product-moment 9254:Statistical functional 9165:Empirical distribution 8998:Controlled experiments 8727:Frequency distribution 8505:Descriptive statistics 8395:List of vaccine topics 7390:Mathematical modelling 7189:Nondestructive testing 7184:Discrimination testing 7138:Standards organization 6834:Number needed to treat 6181:npj Precision Oncology 5244:tuftsctsi.wpengine.com 4077:Clinics in Dermatology 2552:10.1001/jama.2009.1426 2034: 1942: 1538:during epidemics, the 1351:clinical trial portals 1317:information technology 1311:Information technology 1198: 1129: 1011:Active control studies 942: 801: 561:pulmonary tuberculosis 500: 478:essential hypertension 476:from what we now term 474:secondary hypertension 335: 44: 10789:Clinical pharmacology 10784:Design of experiments 10649:Population statistics 10591:System identification 10325:Autocorrelation (ACF) 10253:Exponential smoothing 10167:Discriminant analysis 10162:Canonical correlation 10026:Partition of variance 9888:Regression validation 9732:(Jonckheere–Terpstra) 9631:Likelihood-ratio test 9320:Frequentist inference 9232:Location–scale family 9153:Sampling distribution 9118:Statistical inference 9085:Cross-sectional study 9072:Observational studies 9031:Randomized experiment 8860:Stem-and-leaf display 8662:Central limit theorem 8390:Vaccinate Your Family 7841:Japanese encephalitis 7143:Consumer organization 7131:Testing organizations 6838:Number needed to harm 6725:Cross-sectional study 6677:Scientific experiment 6633:Clinical study design 5868:10.1186/1745-6215-7-9 4580:Moynihan, R. (2003). 3786:on 21 September 2008. 2734:10.5662/wjm.v6.i1.101 2354:10 April 2023 at the 2347:PhRMA. February 2007 2335:23 April 2019 at the 2088:wearable technologies 2032: 1933: 1794:clinical investigator 1196: 1124: 951:observational studies 937: 921:Clinical study design 796: 598:. They carried out a 563:. The trial was both 533:factorial experiments 495: 322: 95:Clinical study design 42: 10572:Probabilistic design 10157:Principal components 10000:Exponential families 9952:Nonlinear regression 9931:General linear model 9893:Mixed effects models 9883:Errors and residuals 9860:Confounding variable 9762:Bayesian probability 9740:Van der Waerden test 9730:Ordered alternative 9495:Multiple comparisons 9374:Rao–Blackwellization 9337:Estimating equations 9293:Statistical distance 9011:Factorial experiment 8544:Arithmetic-Geometric 8273:John Franklin Enders 6804:Cumulative incidence 6440:Front. Public Health 5974:10.1289/ehp.123-A297 5838:on 14 November 2011. 5444:on 17 December 2008. 3202:7 April 2023 at the 2494:; and in Japan, the 2289:(9 September 2015). 2077:Decentralized trials 1691:improve this section 1556:Community engagement 1374:statistical analyses 1347:Statistical software 1250:Nurses' Health Study 1042:squamous cell cancer 873:, usually against a 854:Screening for safety 766:drug is appropriate. 653:interventional study 576:Austin Bradford Hill 497:Austin Bradford Hill 270:Trials of procedures 264:urinary incontinence 232:regulatory authority 183:For a new indication 10644:Official statistics 10567:Methods engineering 10248:Seasonal adjustment 10016:Poisson regressions 9936:Bayesian regression 9875:Regression analysis 9855:Partial correlation 9827:Regression analysis 9426:Prediction interval 9421:Likelihood interval 9411:Confidence interval 9403:Interval estimation 9364:Unbiased estimators 9182:Model specification 9062:Up-and-down designs 8750:Partial correlation 8706:Index of dispersion 8624:Interquartile range 7454:Virus-like particle 7378:Vaccine ingredients 7179:Destructive testing 7169:Conformance testing 6711:Observational study 6643:Real world evidence 6597:experimental design 6103:. 18 January 2019. 5907:on 25 November 2016 5725:10.2196/jmir.7.1.e5 5412:on 15 December 2007 5018:10.1093/ijnp/pyx002 4592:(7400): 1193–1196. 4453:2014Natur.515..177C 4044:10.1200/EDBK_156686 3750:on 13 November 2013 3639:2016PLoSO..1150205E 3128:"Replication study" 2990:Clinical Trials Day 2006:Parkinson's disease 1952:Patient recruitment 1771:Regulatory agencies 1553:Respect for persons 646:observational study 620:prophylactic agents 298:. This is known as 99:scientific validity 97:aims to ensure the 68:dietary supplements 18:Clinical researcher 10799:Medical statistics 10664:Spatial statistics 10544:Medical statistics 10444:First hitting time 10398:Whittle likelihood 10049:Degrees of freedom 10044:Multivariate ANOVA 9977:Heteroscedasticity 9789:Bayesian estimator 9754:Bayesian inference 9603:Kolmogorov–Smirnov 9488:Randomization test 9458:Testing hypotheses 9431:Tolerance interval 9342:Maximum likelihood 9237:Exponential family 9170:Density estimation 9130:Statistical theory 9090:Natural experiment 9036:Scientific control 8953:Survey methodology 8639:Standard deviation 8430:Never to phase III 8229:Hexavalent vaccine 8043:Epstein–Barr virus 7938:Oxford–AstraZeneca 7626:NmVac4-A/C/Y/W-135 7148:Trade organization 6997:Risk–benefit ratio 6964:First-in-man study 6914:Case fatality rate 6755:Case–control study 6729:Longitudinal study 6412:10.1002/cncr.35034 6393:Fleury ME (2023). 6129:. Fox Trial Finder 5824:10.1007/BF03256863 5482:CIOMS Publications 4666:The New York Times 4547:The New York Times 4416:on 2 December 2007 4190:on 4 February 2014 3976:on 2 December 2013 3837:clinicaltrials.gov 3315:10.1007/BF03256820 2387:Powerful Medicines 2296:The New York Times 2067:precision medicine 2035: 2011:ClinicalTrials.gov 1980:Drug abuse testing 1959:medical laboratory 1943: 1486:clinicaltrials.gov 1231:airborne allergies 1199: 1130: 967:case-control study 943: 802: 600:case-control study 569:placebo-controlled 501: 336: 286:will be replaced. 256:open aortic repair 244:premarket approval 180:At varying dosages 80:risk/benefit ratio 52:human participants 45: 10794:Clinical research 10766: 10765: 10704: 10703: 10700: 10699: 10639:National accounts 10609:Actuarial science 10601:Social statistics 10494: 10493: 10490: 10489: 10486: 10485: 10421:Survival function 10406: 10405: 10268:Granger causality 10109:Contingency table 10084:Survival analysis 10061: 10060: 10057: 10056: 9913:Linear regression 9808: 9807: 9804: 9803: 9779:Credible interval 9748: 9747: 9531: 9530: 9347:Method of moments 9216:Parametric family 9177:Statistical model 9107: 9106: 9103: 9102: 9021:Random assignment 8943:Statistical power 8877: 8876: 8873: 8872: 8722:Contingency table 8692: 8691: 8559:Generalized/power 8440: 8439: 8352:Vaccines and SIDS 8239: 8238: 8013:Hepatitis A and B 7989:Varicella zoster 7446:Subunit/component 7300: 7299: 7214:Usability testing 7090: 7089: 7038:Survivorship bias 7002:Systematic review 6969:Multicenter trial 6932: 6931: 6922:Likelihood-ratios 6894:Clinical endpoint 6862:Population impact 6816:Period prevalence 6593:Clinical research 6290:. 14 March 2023. 6155:on 3 October 2013 6016:. 6 August 2022. 5968:(12): A297–A302. 5683:. 17 April 2001. 5328:, 20 March 2001, 5220:on 9 January 2020 5075:10.1111/bdi.12598 5063:Bipolar Disorders 4668:. 16 April 2012. 4110:Khan Y, Tilly S. 3843:on 10 April 2012. 3430:978-0-465-06981-1 3296:Helene S (2010). 3235:10.1136/bmj.g7092 3055:978-0-470-46635-3 3028:978-1-4200-3530-8 2883:978-0-684-87181-3 2836:978-0-19-503568-1 2625:Annals of Surgery 2385:Avorn J. (2004). 2166:"Clinical Trials" 1983:Pregnancy testing 1732:primum non-nocere 1727: 1726: 1719: 1431:compassionate use 1402:Ethics committees 1144:Statistical power 935: 910: 909: 871:"treatment group" 794: 744:Compassionate use 710:radiation therapy 447:Perkin's tractors 296:clinical research 238:Trials of devices 224:diagnostic assays 213:scientific method 168:statistical tests 16:(Redirected from 10811: 10754: 10753: 10742: 10741: 10731: 10730: 10716: 10715: 10619:Crime statistics 10513: 10512: 10500: 10499: 10417: 10416: 10383:Fourier analysis 10370:Frequency domain 10350: 10297: 10263:Structural break 10223: 10222: 10172:Cluster analysis 10119:Log-linear model 10092: 10091: 10067: 10066: 10008: 9982:Homoscedasticity 9838: 9837: 9814: 9813: 9733: 9725: 9717: 9716:(Kruskal–Wallis) 9701: 9686: 9641:Cross validation 9626: 9608:Anderson–Darling 9555: 9542: 9541: 9513:Likelihood-ratio 9505:Parametric tests 9483:Permutation test 9466:1- & 2-tails 9357:Minimum distance 9329:Point estimation 9325: 9324: 9276:Optimal decision 9227: 9126: 9125: 9113: 9112: 9095:Quasi-experiment 9045:Adaptive designs 8896: 8895: 8883: 8882: 8760:Rank correlation 8522: 8521: 8513: 8512: 8500: 8499: 8467: 8460: 8453: 8444: 8443: 8331:MMR autism fraud 8278:Maurice Hilleman 8263:Hilary Koprowski 7571: 7570: 7327: 7320: 7313: 7304: 7303: 7286:Just-About-Right 7255:Software testing 7230:Cannabis testing 7199:Sensory analysis 7117: 7110: 7103: 7094: 7093: 6937:Trial/test types 6812:Point prevalence 6790: 6789: 6733:Ecological study 6716:EBM II-2 to II-3 6687:Open-label trial 6682:Blind experiment 6658:Controlled study 6586: 6579: 6572: 6563: 6562: 6525: 6524: 6514: 6482: 6476: 6475: 6465: 6455: 6431: 6425: 6424: 6414: 6390: 6384: 6383: 6373: 6363: 6339: 6333: 6332: 6330: 6328: 6313: 6304: 6303: 6301: 6299: 6280: 6271: 6270: 6234: 6225: 6224: 6214: 6196: 6171: 6165: 6164: 6162: 6160: 6145: 6139: 6138: 6136: 6134: 6123: 6117: 6116: 6114: 6112: 6098: 6091: 6085: 6084: 6036: 6030: 6029: 6027: 6025: 6010: 6004: 6003: 5993: 5953: 5947: 5946: 5944: 5942: 5923: 5917: 5916: 5914: 5912: 5897: 5891: 5890: 5880: 5870: 5846: 5840: 5839: 5834:. Archived from 5803: 5797: 5796: 5786: 5754: 5748: 5747: 5737: 5727: 5703: 5697: 5696: 5694: 5692: 5673: 5667: 5666: 5648: 5624: 5618: 5617: 5615: 5613: 5598: 5592: 5591: 5589: 5587: 5581: 5574: 5566: 5560: 5559: 5557: 5555: 5549: 5542: 5534: 5528: 5527: 5525: 5523: 5504: 5498: 5497: 5495: 5493: 5474: 5468: 5467: 5466:on 30 June 2007. 5462:. Archived from 5452: 5446: 5445: 5443: 5437:. Archived from 5436: 5428: 5422: 5421: 5419: 5417: 5408:. Archived from 5398: 5392: 5391: 5381: 5371: 5347: 5341: 5340: 5339: 5337: 5316: 5310: 5309: 5307: 5305: 5290: 5284: 5283: 5266: 5260: 5259: 5257: 5255: 5236: 5230: 5229: 5227: 5225: 5216:. Archived from 5206: 5200: 5199: 5189: 5165: 5156: 5155: 5137: 5128:(8): 1879–1884. 5113: 5107: 5106: 5104: 5102: 5054: 5048: 5047: 5037: 4997: 4991: 4990: 4972: 4963:(8): 1879–1884. 4948: 4942: 4941: 4931: 4890: 4884: 4883: 4881: 4879: 4861: 4837: 4831: 4830: 4828: 4826: 4820: 4807: 4799: 4793: 4792: 4790: 4788: 4773: 4767: 4766: 4756: 4732: 4726: 4725: 4688: 4682: 4681: 4679: 4677: 4658: 4652: 4651: 4649: 4647: 4641: 4634: 4626: 4620: 4619: 4609: 4577: 4571: 4570: 4568: 4566: 4538: 4532: 4531: 4529: 4527: 4521: 4490: 4481: 4475: 4474: 4464: 4432: 4426: 4425: 4423: 4421: 4415: 4409:. Archived from 4408: 4400: 4394: 4393: 4383: 4351: 4345: 4344: 4342: 4340: 4322: 4313: 4312: 4306: 4298: 4288: 4248: 4239: 4238: 4236: 4234: 4225:. Archived from 4215: 4209: 4206: 4200: 4199: 4197: 4195: 4180: 4174: 4171: 4165: 4164: 4162: 4160: 4140: 4134: 4133: 4131: 4129: 4123: 4116: 4107: 4101: 4100: 4072: 4066: 4065: 4055: 4023: 4017: 4016: 4014: 4012: 3992: 3986: 3985: 3983: 3981: 3966: 3960: 3959: 3949: 3925: 3919: 3918: 3908: 3876: 3870: 3869: 3851: 3845: 3844: 3839:. Archived from 3829: 3818: 3817: 3815: 3813: 3794: 3788: 3787: 3785: 3779:. Archived from 3774: 3766: 3760: 3759: 3757: 3755: 3739: 3733: 3727: 3726: 3722: 3720: 3718: 3703: 3697: 3696: 3694: 3692: 3683:. 3 March 2017. 3677: 3671: 3670: 3660: 3650: 3618: 3612: 3611: 3593: 3569: 3563: 3562: 3552: 3528: 3517: 3516: 3514: 3512: 3493: 3484: 3483: 3465: 3441: 3435: 3434: 3414: 3408: 3407: 3405: 3403: 3398:on 14 March 2016 3387: 3381: 3380: 3378: 3376: 3361: 3355: 3354: 3352: 3350: 3334: 3328: 3327: 3317: 3293: 3287: 3286: 3284: 3282: 3267: 3258: 3257: 3247: 3237: 3213: 3207: 3193: 3187: 3186: 3150: 3144: 3143: 3141: 3139: 3130:. Archived from 3123: 3117: 3107: 3101: 3100: 3090: 3066: 3060: 3059: 3039: 3033: 3032: 3012: 3006: 3005: 3003: 3001: 2982: 2976: 2975: 2973: 2971: 2956: 2950: 2935: 2929: 2914: 2908: 2894: 2888: 2887: 2859: 2853: 2852: 2850: 2848: 2820: 2807: 2806: 2804: 2802: 2788: 2782: 2781: 2779: 2777: 2763: 2757: 2756: 2746: 2736: 2712: 2706: 2705: 2695: 2663: 2657: 2656: 2620: 2614: 2613: 2603: 2586:(12): CD001756. 2571: 2565: 2564: 2554: 2530: 2524: 2523: 2521: 2519: 2504: 2498: 2476: 2470: 2469: 2467: 2465: 2450: 2425: 2424: 2396: 2390: 2383: 2377: 2364: 2358: 2345: 2339: 2326: 2320: 2319: 2316: 2310: 2308: 2283: 2277: 2276: 2274: 2272: 2261: 2255: 2254: 2252: 2250: 2239: 2233: 2232: 2222: 2194: 2188: 2187: 2185: 2183: 2177: 2170: 2162: 2156: 2155: 2153: 2151: 2136: 2059:machine learning 1853: 1838: 1834: 1800: 1722: 1715: 1711: 1708: 1702: 1671: 1663: 1652:informed consent 1547:Scientific value 1483: 1479: 1409:informed consent 1356: 1280: 1268: 1134:informed consent 1117:Informed consent 936: 840:pharmacokinetics 836:Pharmacodynamics 818: 817: 806:drug development 795: 617: 505:Ronald A. Fisher 383:circumnavigation 360:smallpox vaccine 248:vascular surgery 105:of the results. 91:multiple centers 21: 10819: 10818: 10814: 10813: 10812: 10810: 10809: 10808: 10779:Clinical trials 10769: 10768: 10767: 10762: 10725: 10696: 10658: 10595: 10581:quality control 10548: 10530:Clinical trials 10507: 10482: 10466: 10454:Hazard function 10448: 10402: 10364: 10348: 10311: 10307:Breusch–Godfrey 10295: 10272: 10212: 10187:Factor analysis 10133: 10114:Graphical model 10086: 10053: 10020: 10006: 9986: 9940: 9907: 9869: 9832: 9831: 9800: 9744: 9731: 9723: 9715: 9699: 9684: 9663:Rank statistics 9657: 9636:Model selection 9624: 9582:Goodness of fit 9576: 9553: 9527: 9499: 9452: 9397: 9386:Median unbiased 9314: 9225: 9158:Order statistic 9120: 9099: 9066: 9040: 8992: 8947: 8890: 8888:Data collection 8869: 8781: 8736: 8710: 8688: 8648: 8600: 8517:Continuous data 8507: 8494: 8476: 8471: 8441: 8436: 8435: 8420:Clinical trials 8399: 8368: 8307: 8283:Stanley Plotkin 8245: 8235: 8147:Cancer vaccines 8130: 8124:Schistosomiasis 8102: 8096:Trypanosomiasis 8069: 8033:Cytomegalovirus 7943:Pfizer–BioNTech 7738: 7562: 7511:Vaccine wastage 7481: 7409: 7361: 7331: 7301: 7296: 7269: 7250:Package testing 7218: 7204:Survey research 7157: 7126: 7124:Product testing 7121: 7091: 7086: 7057: 7021: 6983: 6928: 6882: 6856: 6830:Risk difference 6818: 6779: 6713: 6705: 6660: 6652: 6616:Trial protocols 6599: 6590: 6534: 6529: 6528: 6483: 6479: 6432: 6428: 6391: 6387: 6348:Genome Medicine 6340: 6336: 6326: 6324: 6315: 6314: 6307: 6297: 6295: 6282: 6281: 6274: 6235: 6228: 6172: 6168: 6158: 6156: 6147: 6146: 6142: 6132: 6130: 6125: 6124: 6120: 6110: 6108: 6101:Financial Times 6093: 6092: 6088: 6037: 6033: 6023: 6021: 6012: 6011: 6007: 5954: 5950: 5940: 5938: 5925: 5924: 5920: 5910: 5908: 5899: 5898: 5894: 5847: 5843: 5804: 5800: 5755: 5751: 5704: 5700: 5690: 5688: 5675: 5674: 5670: 5633:Clinical Trials 5625: 5621: 5611: 5609: 5600: 5599: 5595: 5585: 5583: 5579: 5572: 5568: 5567: 5563: 5553: 5551: 5547: 5540: 5536: 5535: 5531: 5521: 5519: 5506: 5505: 5501: 5491: 5489: 5476: 5475: 5471: 5454: 5453: 5449: 5441: 5434: 5430: 5429: 5425: 5415: 5413: 5400: 5399: 5395: 5362:(6): e1001228. 5348: 5344: 5335: 5333: 5318: 5317: 5313: 5303: 5301: 5292: 5291: 5287: 5280: 5268: 5267: 5263: 5253: 5251: 5246:. 15 May 2018. 5238: 5237: 5233: 5223: 5221: 5208: 5207: 5203: 5166: 5159: 5114: 5110: 5100: 5098: 5055: 5051: 4998: 4994: 4949: 4945: 4891: 4887: 4877: 4875: 4838: 4834: 4824: 4822: 4818: 4805: 4801: 4800: 4796: 4786: 4784: 4775: 4774: 4770: 4733: 4729: 4689: 4685: 4675: 4673: 4660: 4659: 4655: 4645: 4643: 4642:on 25 June 2008 4639: 4632: 4628: 4627: 4623: 4578: 4574: 4564: 4562: 4539: 4535: 4525: 4523: 4519: 4488: 4482: 4478: 4462:10.1038/515177a 4447:(7526): 177–8. 4433: 4429: 4419: 4417: 4413: 4406: 4402: 4401: 4397: 4352: 4348: 4338: 4336: 4323: 4316: 4300: 4299: 4249: 4242: 4232: 4230: 4217: 4216: 4212: 4207: 4203: 4193: 4191: 4182: 4181: 4177: 4172: 4168: 4158: 4156: 4149:Clinical Leader 4141: 4137: 4127: 4125: 4124:on 15 July 2011 4121: 4114: 4108: 4104: 4073: 4069: 4024: 4020: 4010: 4008: 4001:Clinical Leader 3993: 3989: 3979: 3977: 3968: 3967: 3963: 3926: 3922: 3877: 3873: 3866: 3852: 3848: 3831: 3830: 3821: 3811: 3809: 3796: 3795: 3791: 3783: 3772: 3768: 3767: 3763: 3753: 3751: 3740: 3736: 3724: 3716: 3714: 3705: 3704: 3700: 3690: 3688: 3679: 3678: 3674: 3633:(3): e0150205. 3619: 3615: 3570: 3566: 3529: 3520: 3510: 3508: 3495: 3494: 3487: 3442: 3438: 3431: 3423:. Basic Books. 3415: 3411: 3401: 3399: 3388: 3384: 3374: 3372: 3363: 3362: 3358: 3348: 3346: 3335: 3331: 3294: 3290: 3280: 3278: 3269: 3268: 3261: 3214: 3210: 3204:Wayback Machine 3194: 3190: 3151: 3147: 3137: 3135: 3124: 3120: 3108: 3104: 3067: 3063: 3056: 3040: 3036: 3029: 3013: 3009: 2999: 2997: 2984: 2983: 2979: 2969: 2967: 2958: 2957: 2953: 2936: 2932: 2915: 2911: 2895: 2891: 2884: 2860: 2856: 2846: 2844: 2837: 2821: 2810: 2800: 2798: 2790: 2789: 2785: 2775: 2773: 2765: 2764: 2760: 2713: 2709: 2678:(1): CD003857. 2664: 2660: 2621: 2617: 2572: 2568: 2545:(14): 1535–42. 2531: 2527: 2517: 2515: 2506: 2505: 2501: 2477: 2473: 2463: 2461: 2452: 2451: 2428: 2407:(11): 1233–40. 2397: 2393: 2384: 2380: 2375:Wayback Machine 2365: 2361: 2356:Wayback Machine 2346: 2342: 2337:Wayback Machine 2327: 2323: 2314: 2306: 2304: 2284: 2280: 2270: 2268: 2263: 2262: 2258: 2248: 2246: 2241: 2240: 2236: 2195: 2191: 2181: 2179: 2175: 2168: 2164: 2163: 2159: 2149: 2147: 2138: 2137: 2128: 2123: 2100:Outcome measure 2096: 2079: 2044: 2027: 1998: 1996:Locating trials 1948:ethnic minority 1928: 1919: 1910: 1898:orphan diseases 1851: 1845: 1836: 1832: 1829: 1820: 1798: 1775:In the US, the 1773: 1755:Approval by an 1753: 1723: 1712: 1706: 1703: 1688: 1672: 1661: 1622: 1597: 1583: 1573: 1568: 1535: 1481: 1477: 1466: 1456:through public 1435:Expanded access 1393: 1385:Main articles: 1383: 1381:Ethical aspects 1370: 1364: 1354: 1313: 1304: 1296: 1278: 1271:data collection 1266: 1258: 1191: 1172: 1166: 1146: 1127:PARAMOUNT trial 1119: 1114: 1112:Design features 1056: 1050: 1037:Genetic testing 1026: 1024:Master protocol 1013: 925: 923: 917: 784: 782: 776: 748:expanded access 737:Epidemiological 722:chronic illness 717:Quality of life 638: 615: 614:called him "... 490: 317: 312: 292: 272: 240: 136: 134:Trials of drugs 131: 103:reproducibility 72:medical devices 64:dietary choices 48:Clinical trials 35: 28: 23: 22: 15: 12: 11: 5: 10817: 10807: 10806: 10804:Drug discovery 10801: 10796: 10791: 10786: 10781: 10764: 10763: 10761: 10760: 10748: 10736: 10722: 10709: 10706: 10705: 10702: 10701: 10698: 10697: 10695: 10694: 10689: 10684: 10679: 10674: 10668: 10666: 10660: 10659: 10657: 10656: 10651: 10646: 10641: 10636: 10631: 10626: 10621: 10616: 10611: 10605: 10603: 10597: 10596: 10594: 10593: 10588: 10583: 10574: 10569: 10564: 10558: 10556: 10550: 10549: 10547: 10546: 10541: 10536: 10527: 10525:Bioinformatics 10521: 10519: 10509: 10508: 10496: 10495: 10492: 10491: 10488: 10487: 10484: 10483: 10481: 10480: 10474: 10472: 10468: 10467: 10465: 10464: 10458: 10456: 10450: 10449: 10447: 10446: 10441: 10436: 10431: 10425: 10423: 10414: 10408: 10407: 10404: 10403: 10401: 10400: 10395: 10390: 10385: 10380: 10374: 10372: 10366: 10365: 10363: 10362: 10357: 10352: 10344: 10339: 10334: 10333: 10332: 10330:partial (PACF) 10321: 10319: 10313: 10312: 10310: 10309: 10304: 10299: 10291: 10286: 10280: 10278: 10277:Specific tests 10274: 10273: 10271: 10270: 10265: 10260: 10255: 10250: 10245: 10240: 10235: 10229: 10227: 10220: 10214: 10213: 10211: 10210: 10209: 10208: 10207: 10206: 10191: 10190: 10189: 10179: 10177:Classification 10174: 10169: 10164: 10159: 10154: 10149: 10143: 10141: 10135: 10134: 10132: 10131: 10126: 10124:McNemar's test 10121: 10116: 10111: 10106: 10100: 10098: 10088: 10087: 10063: 10062: 10059: 10058: 10055: 10054: 10052: 10051: 10046: 10041: 10036: 10030: 10028: 10022: 10021: 10019: 10018: 10002: 9996: 9994: 9988: 9987: 9985: 9984: 9979: 9974: 9969: 9964: 9962:Semiparametric 9959: 9954: 9948: 9946: 9942: 9941: 9939: 9938: 9933: 9928: 9923: 9917: 9915: 9909: 9908: 9906: 9905: 9900: 9895: 9890: 9885: 9879: 9877: 9871: 9870: 9868: 9867: 9862: 9857: 9852: 9846: 9844: 9834: 9833: 9830: 9829: 9824: 9818: 9810: 9809: 9806: 9805: 9802: 9801: 9799: 9798: 9797: 9796: 9786: 9781: 9776: 9775: 9774: 9769: 9758: 9756: 9750: 9749: 9746: 9745: 9743: 9742: 9737: 9736: 9735: 9727: 9719: 9703: 9700:(Mann–Whitney) 9695: 9694: 9693: 9680: 9679: 9678: 9667: 9665: 9659: 9658: 9656: 9655: 9654: 9653: 9648: 9643: 9633: 9628: 9625:(Shapiro–Wilk) 9620: 9615: 9610: 9605: 9600: 9592: 9586: 9584: 9578: 9577: 9575: 9574: 9566: 9557: 9545: 9539: 9537:Specific tests 9533: 9532: 9529: 9528: 9526: 9525: 9520: 9515: 9509: 9507: 9501: 9500: 9498: 9497: 9492: 9491: 9490: 9480: 9479: 9478: 9468: 9462: 9460: 9454: 9453: 9451: 9450: 9449: 9448: 9443: 9433: 9428: 9423: 9418: 9413: 9407: 9405: 9399: 9398: 9396: 9395: 9390: 9389: 9388: 9383: 9382: 9381: 9376: 9361: 9360: 9359: 9354: 9349: 9344: 9333: 9331: 9322: 9316: 9315: 9313: 9312: 9307: 9302: 9301: 9300: 9290: 9285: 9284: 9283: 9273: 9272: 9271: 9266: 9261: 9251: 9246: 9241: 9240: 9239: 9234: 9229: 9213: 9212: 9211: 9206: 9201: 9191: 9190: 9189: 9184: 9174: 9173: 9172: 9162: 9161: 9160: 9150: 9145: 9140: 9134: 9132: 9122: 9121: 9109: 9108: 9105: 9104: 9101: 9100: 9098: 9097: 9092: 9087: 9082: 9076: 9074: 9068: 9067: 9065: 9064: 9059: 9054: 9048: 9046: 9042: 9041: 9039: 9038: 9033: 9028: 9023: 9018: 9013: 9008: 9002: 9000: 8994: 8993: 8991: 8990: 8988:Standard error 8985: 8980: 8975: 8974: 8973: 8968: 8957: 8955: 8949: 8948: 8946: 8945: 8940: 8935: 8930: 8925: 8920: 8918:Optimal design 8915: 8910: 8904: 8902: 8892: 8891: 8879: 8878: 8875: 8874: 8871: 8870: 8868: 8867: 8862: 8857: 8852: 8847: 8842: 8837: 8832: 8827: 8822: 8817: 8812: 8807: 8802: 8797: 8791: 8789: 8783: 8782: 8780: 8779: 8774: 8773: 8772: 8767: 8757: 8752: 8746: 8744: 8738: 8737: 8735: 8734: 8729: 8724: 8718: 8716: 8715:Summary tables 8712: 8711: 8709: 8708: 8702: 8700: 8694: 8693: 8690: 8689: 8687: 8686: 8685: 8684: 8679: 8674: 8664: 8658: 8656: 8650: 8649: 8647: 8646: 8641: 8636: 8631: 8626: 8621: 8616: 8610: 8608: 8602: 8601: 8599: 8598: 8593: 8588: 8587: 8586: 8581: 8576: 8571: 8566: 8561: 8556: 8551: 8549:Contraharmonic 8546: 8541: 8530: 8528: 8519: 8509: 8508: 8496: 8495: 8493: 8492: 8487: 8481: 8478: 8477: 8470: 8469: 8462: 8455: 8447: 8438: 8437: 8434: 8433: 8432: 8431: 8428: 8417: 8411: 8405: 8404: 8401: 8400: 8398: 8397: 8392: 8387: 8382: 8376: 8374: 8370: 8369: 8367: 8366: 8361: 8354: 8349: 8344: 8339: 8334: 8321: 8315: 8313: 8309: 8308: 8306: 8305: 8300: 8298:Katalin Karikó 8295: 8290: 8285: 8280: 8275: 8270: 8265: 8260: 8255: 8249: 8247: 8241: 8240: 8237: 8236: 8234: 8233: 8232: 8231: 8226: 8221: 8216: 8208: 8203: 8198: 8193: 8188: 8187: 8186: 8181: 8180: 8179: 8174: 8164: 8159: 8154: 8144: 8138: 8136: 8132: 8131: 8129: 8128: 8127: 8126: 8121: 8112: 8110: 8104: 8103: 8101: 8100: 8099: 8098: 8090: 8089: 8088: 8077: 8075: 8071: 8070: 8068: 8067: 8066: 8065: 8060: 8055: 8053:Herpes simplex 8050: 8045: 8040: 8035: 8027: 8026: 8025: 8020: 8015: 8007: 8002: 8001: 8000: 7995: 7987: 7982: 7977: 7972: 7971: 7970: 7965: 7960: 7955: 7953:Sinopharm BIBP 7950: 7945: 7940: 7935: 7930: 7925: 7920: 7915: 7910: 7905: 7903:Bharat Biotech 7900: 7890: 7885: 7880: 7875: 7874: 7873: 7868: 7858: 7853: 7848: 7843: 7838: 7837: 7836: 7831: 7821: 7816: 7811: 7806: 7801: 7800: 7799: 7794: 7789: 7784: 7769: 7768: 7767: 7757: 7752: 7746: 7744: 7740: 7739: 7737: 7736: 7735: 7734: 7729: 7724: 7716: 7715: 7714: 7709: 7701: 7696: 7695: 7694: 7689: 7679: 7678: 7677: 7667: 7662: 7657: 7656: 7655: 7650: 7640: 7635: 7630: 7629: 7628: 7623: 7613: 7608: 7603: 7598: 7593: 7588: 7583: 7577: 7575: 7568: 7564: 7563: 7561: 7560: 7559: 7558: 7553: 7548: 7543: 7538: 7530: 7529: 7528: 7526:Vaccine injury 7523: 7518: 7513: 7508: 7503: 7498: 7489: 7487: 7486:Administration 7483: 7482: 7480: 7479: 7474: 7469: 7460: 7443: 7442: 7441: 7436: 7428: 7423: 7417: 7415: 7411: 7410: 7408: 7407: 7402: 7397: 7392: 7387: 7386: 7385: 7375: 7369: 7367: 7363: 7362: 7330: 7329: 7322: 7315: 7307: 7298: 7297: 7295: 7294: 7289: 7283: 7277: 7275: 7271: 7270: 7268: 7267: 7262: 7260:Whisky tasting 7257: 7252: 7247: 7245:Clinical trial 7242: 7237: 7235:Coffee cupping 7232: 7226: 7224: 7223:Product fields 7220: 7219: 7217: 7216: 7211: 7206: 7201: 7196: 7191: 7186: 7181: 7176: 7171: 7165: 7163: 7159: 7158: 7156: 7155: 7150: 7145: 7140: 7134: 7132: 7128: 7127: 7120: 7119: 7112: 7105: 7097: 7088: 7087: 7085: 7084: 7081:List of topics 7077: 7070: 7062: 7059: 7058: 7056: 7055: 7050: 7045: 7040: 7035: 7033:Selection bias 7029: 7027: 7023: 7022: 7020: 7019: 7014: 7009: 7004: 6999: 6993: 6991: 6985: 6984: 6982: 6981: 6976: 6971: 6966: 6961: 6956: 6954:Animal testing 6951: 6946: 6940: 6938: 6934: 6933: 6930: 6929: 6906:Mortality rate 6892: 6890: 6884: 6883: 6866: 6864: 6858: 6857: 6828: 6826: 6820: 6819: 6798: 6796: 6787: 6781: 6780: 6778: 6777: 6772: 6767: 6762: 6752: 6751: 6750: 6745: 6735: 6721: 6719: 6707: 6706: 6704: 6703: 6702: 6701: 6699:Platform trial 6691: 6690: 6689: 6684: 6679: 6668: 6666: 6654: 6653: 6651: 6650: 6645: 6640: 6635: 6630: 6625: 6624: 6623: 6618: 6611:Clinical trial 6607: 6605: 6601: 6600: 6589: 6588: 6581: 6574: 6566: 6560: 6559: 6553: 6547: 6541: 6533: 6532:External links 6530: 6527: 6526: 6497:(4): 384–387. 6477: 6426: 6385: 6334: 6305: 6272: 6226: 6166: 6140: 6118: 6086: 6051:(7): 656–662. 6031: 6005: 5948: 5918: 5892: 5841: 5818:(4): 215–222. 5798: 5769:(3): 342–352. 5749: 5698: 5668: 5639:(2): 117–126. 5619: 5593: 5561: 5529: 5499: 5469: 5447: 5423: 5393: 5342: 5311: 5285: 5278: 5261: 5231: 5201: 5180:(1): 475–494. 5157: 5108: 5069:(2): 171–172. 5049: 4992: 4943: 4906:(5): 424–429. 4885: 4832: 4794: 4768: 4727: 4700:(6): 1175–82. 4683: 4653: 4621: 4572: 4533: 4499:(2): 121–141. 4476: 4427: 4395: 4366:(4): 285–309. 4346: 4314: 4240: 4229:on 21 May 2015 4210: 4201: 4175: 4166: 4135: 4102: 4067: 4018: 3987: 3961: 3920: 3891:(2): 619–620. 3871: 3864: 3846: 3819: 3789: 3761: 3742:Young, Susan. 3734: 3698: 3672: 3613: 3584:(4): 1043–51. 3564: 3518: 3485: 3436: 3429: 3409: 3382: 3356: 3329: 3308:(4): 223–229. 3288: 3259: 3208: 3188: 3145: 3134:on 2 June 2012 3118: 3102: 3061: 3054: 3034: 3027: 3007: 2977: 2951: 2930: 2909: 2889: 2882: 2854: 2835: 2808: 2783: 2758: 2707: 2658: 2615: 2566: 2525: 2499: 2488:European Union 2471: 2426: 2391: 2378: 2359: 2340: 2321: 2278: 2256: 2234: 2189: 2157: 2125: 2124: 2122: 2119: 2118: 2117: 2112: 2107: 2105:Odds algorithm 2102: 2095: 2092: 2078: 2075: 2074: 2073: 2070: 2052: 2043: 2040: 2026: 2023: 1997: 1994: 1985: 1984: 1981: 1978: 1975: 1974:Urine sampling 1972: 1971:Blood sampling 1969: 1966: 1927: 1924: 1918: 1915: 1909: 1906: 1887: 1886: 1883: 1880: 1877: 1874: 1871: 1868: 1865: 1862: 1859: 1844: 1841: 1828: 1825: 1819: 1816: 1772: 1769: 1752: 1749: 1725: 1724: 1675: 1673: 1666: 1660: 1657: 1640:adverse events 1621: 1618: 1596: 1593: 1572: 1569: 1567: 1566: 1563: 1560: 1557: 1554: 1551: 1548: 1544: 1534: 1531: 1503:Seeding trials 1465: 1462: 1439:Odds algorithm 1382: 1379: 1363: 1360: 1312: 1309: 1303: 1300: 1295: 1292: 1257: 1256:Administration 1254: 1219: 1218: 1214: 1210: 1190: 1187: 1168:Main article: 1165: 1164:Placebo groups 1162: 1145: 1142: 1118: 1115: 1113: 1110: 1052:Main article: 1049: 1046: 1031:platform trial 1025: 1022: 1012: 1009: 1000: 999: 996:placebo effect 992: 988: 961:, such as the 919:Main article: 916: 913: 912: 911: 908: 907: 904: 901: 897: 896: 892: 889: 885: 884: 883:side effects. 880: 867: 863: 862: 855: 852: 848: 847: 843: 833: 829: 828: 825: 822: 778:Main article: 775: 772: 768: 767: 755: 752: 741: 733: 725: 713: 703: 697: 691: 680:micronutrients 657: 656: 649: 637: 634: 489: 486: 462:Guy's Hospital 454:in the 1860s. 442:placebo effect 402:clinical trial 369:. The disease 316: 313: 311: 308: 304:plain language 291: 288: 271: 268: 239: 236: 191: 190: 187: 184: 181: 178: 135: 132: 130: 127: 123:approved drugs 111:pharmaceutical 26: 9: 6: 4: 3: 2: 10816: 10805: 10802: 10800: 10797: 10795: 10792: 10790: 10787: 10785: 10782: 10780: 10777: 10776: 10774: 10759: 10758: 10749: 10747: 10746: 10737: 10735: 10734: 10729: 10723: 10721: 10720: 10711: 10710: 10707: 10693: 10690: 10688: 10687:Geostatistics 10685: 10683: 10680: 10678: 10675: 10673: 10670: 10669: 10667: 10665: 10661: 10655: 10654:Psychometrics 10652: 10650: 10647: 10645: 10642: 10640: 10637: 10635: 10632: 10630: 10627: 10625: 10622: 10620: 10617: 10615: 10612: 10610: 10607: 10606: 10604: 10602: 10598: 10592: 10589: 10587: 10584: 10582: 10578: 10575: 10573: 10570: 10568: 10565: 10563: 10560: 10559: 10557: 10555: 10551: 10545: 10542: 10540: 10537: 10535: 10531: 10528: 10526: 10523: 10522: 10520: 10518: 10517:Biostatistics 10514: 10510: 10506: 10501: 10497: 10479: 10478:Log-rank test 10476: 10475: 10473: 10469: 10463: 10460: 10459: 10457: 10455: 10451: 10445: 10442: 10440: 10437: 10435: 10432: 10430: 10427: 10426: 10424: 10422: 10418: 10415: 10413: 10409: 10399: 10396: 10394: 10391: 10389: 10386: 10384: 10381: 10379: 10376: 10375: 10373: 10371: 10367: 10361: 10358: 10356: 10353: 10351: 10349:(Box–Jenkins) 10345: 10343: 10340: 10338: 10335: 10331: 10328: 10327: 10326: 10323: 10322: 10320: 10318: 10314: 10308: 10305: 10303: 10302:Durbin–Watson 10300: 10298: 10292: 10290: 10287: 10285: 10284:Dickey–Fuller 10282: 10281: 10279: 10275: 10269: 10266: 10264: 10261: 10259: 10258:Cointegration 10256: 10254: 10251: 10249: 10246: 10244: 10241: 10239: 10236: 10234: 10233:Decomposition 10231: 10230: 10228: 10224: 10221: 10219: 10215: 10205: 10202: 10201: 10200: 10197: 10196: 10195: 10192: 10188: 10185: 10184: 10183: 10180: 10178: 10175: 10173: 10170: 10168: 10165: 10163: 10160: 10158: 10155: 10153: 10150: 10148: 10145: 10144: 10142: 10140: 10136: 10130: 10127: 10125: 10122: 10120: 10117: 10115: 10112: 10110: 10107: 10105: 10104:Cohen's kappa 10102: 10101: 10099: 10097: 10093: 10089: 10085: 10081: 10077: 10073: 10068: 10064: 10050: 10047: 10045: 10042: 10040: 10037: 10035: 10032: 10031: 10029: 10027: 10023: 10017: 10013: 10009: 10003: 10001: 9998: 9997: 9995: 9993: 9989: 9983: 9980: 9978: 9975: 9973: 9970: 9968: 9965: 9963: 9960: 9958: 9957:Nonparametric 9955: 9953: 9950: 9949: 9947: 9943: 9937: 9934: 9932: 9929: 9927: 9924: 9922: 9919: 9918: 9916: 9914: 9910: 9904: 9901: 9899: 9896: 9894: 9891: 9889: 9886: 9884: 9881: 9880: 9878: 9876: 9872: 9866: 9863: 9861: 9858: 9856: 9853: 9851: 9848: 9847: 9845: 9843: 9839: 9835: 9828: 9825: 9823: 9820: 9819: 9815: 9811: 9795: 9792: 9791: 9790: 9787: 9785: 9782: 9780: 9777: 9773: 9770: 9768: 9765: 9764: 9763: 9760: 9759: 9757: 9755: 9751: 9741: 9738: 9734: 9728: 9726: 9720: 9718: 9712: 9711: 9710: 9707: 9706:Nonparametric 9704: 9702: 9696: 9692: 9689: 9688: 9687: 9681: 9677: 9676:Sample median 9674: 9673: 9672: 9669: 9668: 9666: 9664: 9660: 9652: 9649: 9647: 9644: 9642: 9639: 9638: 9637: 9634: 9632: 9629: 9627: 9621: 9619: 9616: 9614: 9611: 9609: 9606: 9604: 9601: 9599: 9597: 9593: 9591: 9588: 9587: 9585: 9583: 9579: 9573: 9571: 9567: 9565: 9563: 9558: 9556: 9551: 9547: 9546: 9543: 9540: 9538: 9534: 9524: 9521: 9519: 9516: 9514: 9511: 9510: 9508: 9506: 9502: 9496: 9493: 9489: 9486: 9485: 9484: 9481: 9477: 9474: 9473: 9472: 9469: 9467: 9464: 9463: 9461: 9459: 9455: 9447: 9444: 9442: 9439: 9438: 9437: 9434: 9432: 9429: 9427: 9424: 9422: 9419: 9417: 9414: 9412: 9409: 9408: 9406: 9404: 9400: 9394: 9391: 9387: 9384: 9380: 9377: 9375: 9372: 9371: 9370: 9367: 9366: 9365: 9362: 9358: 9355: 9353: 9350: 9348: 9345: 9343: 9340: 9339: 9338: 9335: 9334: 9332: 9330: 9326: 9323: 9321: 9317: 9311: 9308: 9306: 9303: 9299: 9296: 9295: 9294: 9291: 9289: 9286: 9282: 9281:loss function 9279: 9278: 9277: 9274: 9270: 9267: 9265: 9262: 9260: 9257: 9256: 9255: 9252: 9250: 9247: 9245: 9242: 9238: 9235: 9233: 9230: 9228: 9222: 9219: 9218: 9217: 9214: 9210: 9207: 9205: 9202: 9200: 9197: 9196: 9195: 9192: 9188: 9185: 9183: 9180: 9179: 9178: 9175: 9171: 9168: 9167: 9166: 9163: 9159: 9156: 9155: 9154: 9151: 9149: 9146: 9144: 9141: 9139: 9136: 9135: 9133: 9131: 9127: 9123: 9119: 9114: 9110: 9096: 9093: 9091: 9088: 9086: 9083: 9081: 9078: 9077: 9075: 9073: 9069: 9063: 9060: 9058: 9055: 9053: 9050: 9049: 9047: 9043: 9037: 9034: 9032: 9029: 9027: 9024: 9022: 9019: 9017: 9014: 9012: 9009: 9007: 9004: 9003: 9001: 8999: 8995: 8989: 8986: 8984: 8983:Questionnaire 8981: 8979: 8976: 8972: 8969: 8967: 8964: 8963: 8962: 8959: 8958: 8956: 8954: 8950: 8944: 8941: 8939: 8936: 8934: 8931: 8929: 8926: 8924: 8921: 8919: 8916: 8914: 8911: 8909: 8906: 8905: 8903: 8901: 8897: 8893: 8889: 8884: 8880: 8866: 8863: 8861: 8858: 8856: 8853: 8851: 8848: 8846: 8843: 8841: 8838: 8836: 8833: 8831: 8828: 8826: 8823: 8821: 8818: 8816: 8813: 8811: 8810:Control chart 8808: 8806: 8803: 8801: 8798: 8796: 8793: 8792: 8790: 8788: 8784: 8778: 8775: 8771: 8768: 8766: 8763: 8762: 8761: 8758: 8756: 8753: 8751: 8748: 8747: 8745: 8743: 8739: 8733: 8730: 8728: 8725: 8723: 8720: 8719: 8717: 8713: 8707: 8704: 8703: 8701: 8699: 8695: 8683: 8680: 8678: 8675: 8673: 8670: 8669: 8668: 8665: 8663: 8660: 8659: 8657: 8655: 8651: 8645: 8642: 8640: 8637: 8635: 8632: 8630: 8627: 8625: 8622: 8620: 8617: 8615: 8612: 8611: 8609: 8607: 8603: 8597: 8594: 8592: 8589: 8585: 8582: 8580: 8577: 8575: 8572: 8570: 8567: 8565: 8562: 8560: 8557: 8555: 8552: 8550: 8547: 8545: 8542: 8540: 8537: 8536: 8535: 8532: 8531: 8529: 8527: 8523: 8520: 8518: 8514: 8510: 8506: 8501: 8497: 8491: 8488: 8486: 8483: 8482: 8479: 8475: 8468: 8463: 8461: 8456: 8454: 8449: 8448: 8445: 8429: 8427: 8424: 8423: 8421: 8418: 8415: 8412: 8410: 8407: 8406: 8402: 8396: 8393: 8391: 8388: 8386: 8383: 8381: 8378: 8377: 8375: 8371: 8365: 8362: 8360: 8359: 8355: 8353: 8350: 8348: 8345: 8343: 8340: 8338: 8335: 8332: 8330: 8325: 8322: 8320: 8317: 8316: 8314: 8310: 8304: 8303:Drew Weissman 8301: 8299: 8296: 8294: 8291: 8289: 8288:H. Fred Clark 8286: 8284: 8281: 8279: 8276: 8274: 8271: 8269: 8266: 8264: 8261: 8259: 8258:Louis Pasteur 8256: 8254: 8253:Edward Jenner 8251: 8250: 8248: 8242: 8230: 8227: 8225: 8224:DTwP-HepB-Hib 8222: 8220: 8219:DTaP-IPV-HepB 8217: 8215: 8212: 8211: 8210:combination: 8209: 8207: 8204: 8202: 8199: 8197: 8194: 8192: 8189: 8185: 8182: 8178: 8175: 8173: 8170: 8169: 8168: 8165: 8163: 8160: 8158: 8155: 8153: 8150: 8149: 8148: 8145: 8143: 8140: 8139: 8137: 8133: 8125: 8122: 8120: 8117: 8116: 8114: 8113: 8111: 8109: 8108:Helminthiasis 8105: 8097: 8094: 8093: 8091: 8087: 8084: 8083: 8082: 8079: 8078: 8076: 8072: 8064: 8061: 8059: 8056: 8054: 8051: 8049: 8046: 8044: 8041: 8039: 8036: 8034: 8031: 8030: 8028: 8024: 8021: 8019: 8016: 8014: 8011: 8010: 8009:combination: 8008: 8006: 8003: 7999: 7996: 7994: 7991: 7990: 7988: 7986: 7983: 7981: 7978: 7976: 7973: 7969: 7966: 7964: 7961: 7959: 7956: 7954: 7951: 7949: 7946: 7944: 7941: 7939: 7936: 7934: 7931: 7929: 7926: 7924: 7921: 7919: 7916: 7914: 7911: 7909: 7906: 7904: 7901: 7899: 7896: 7895: 7894: 7891: 7889: 7886: 7884: 7881: 7879: 7876: 7872: 7869: 7867: 7864: 7863: 7862: 7859: 7857: 7854: 7852: 7849: 7847: 7844: 7842: 7839: 7835: 7832: 7830: 7827: 7826: 7825: 7822: 7820: 7817: 7815: 7812: 7810: 7807: 7805: 7802: 7798: 7795: 7793: 7790: 7788: 7785: 7782: 7778: 7775: 7774: 7773: 7770: 7766: 7763: 7762: 7761: 7758: 7756: 7753: 7751: 7748: 7747: 7745: 7741: 7733: 7730: 7728: 7725: 7723: 7720: 7719: 7717: 7713: 7710: 7708: 7707:DPT/DTwP/DTaP 7705: 7704: 7703:combination: 7702: 7700: 7697: 7693: 7690: 7688: 7685: 7684: 7683: 7680: 7676: 7673: 7672: 7671: 7668: 7666: 7663: 7661: 7658: 7654: 7651: 7649: 7646: 7645: 7644: 7641: 7639: 7636: 7634: 7631: 7627: 7624: 7622: 7619: 7618: 7617: 7616:Meningococcus 7614: 7612: 7609: 7607: 7606:Leptospirosis 7604: 7602: 7599: 7597: 7594: 7592: 7589: 7587: 7584: 7582: 7579: 7578: 7576: 7572: 7569: 7565: 7557: 7554: 7552: 7549: 7547: 7544: 7542: 7541:Vaccine court 7539: 7537: 7534: 7533: 7531: 7527: 7524: 7522: 7519: 7517: 7514: 7512: 7509: 7507: 7504: 7502: 7499: 7497: 7496:GAVI Alliance 7494: 7493: 7491: 7490: 7488: 7484: 7478: 7475: 7473: 7470: 7468: 7464: 7461: 7459: 7455: 7451: 7447: 7444: 7440: 7437: 7435: 7432: 7431: 7429: 7427: 7424: 7422: 7419: 7418: 7416: 7412: 7406: 7403: 7401: 7398: 7396: 7393: 7391: 7388: 7384: 7381: 7380: 7379: 7376: 7374: 7371: 7370: 7368: 7364: 7359: 7355: 7351: 7347: 7343: 7339: 7335: 7328: 7323: 7321: 7316: 7314: 7309: 7308: 7305: 7293: 7290: 7287: 7284: 7282: 7279: 7278: 7276: 7272: 7266: 7263: 7261: 7258: 7256: 7253: 7251: 7248: 7246: 7243: 7241: 7238: 7236: 7233: 7231: 7228: 7227: 7225: 7221: 7215: 7212: 7210: 7207: 7205: 7202: 7200: 7197: 7195: 7194:Physical test 7192: 7190: 7187: 7185: 7182: 7180: 7177: 7175: 7174:Chemical test 7172: 7170: 7167: 7166: 7164: 7162:Methodologies 7160: 7154: 7151: 7149: 7146: 7144: 7141: 7139: 7136: 7135: 7133: 7129: 7125: 7118: 7113: 7111: 7106: 7104: 7099: 7098: 7095: 7083: 7082: 7078: 7076: 7075: 7071: 7069: 7068: 7064: 7063: 7060: 7054: 7051: 7049: 7046: 7044: 7041: 7039: 7036: 7034: 7031: 7030: 7028: 7024: 7018: 7015: 7013: 7012:Meta-analysis 7010: 7008: 7005: 7003: 7000: 6998: 6995: 6994: 6992: 6990: 6986: 6980: 6979:Vaccine trial 6977: 6975: 6974:Seeding trial 6972: 6970: 6967: 6965: 6962: 6960: 6957: 6955: 6952: 6950: 6947: 6945: 6942: 6941: 6939: 6935: 6927: 6923: 6919: 6915: 6911: 6907: 6903: 6899: 6895: 6891: 6889: 6885: 6881: 6877: 6873: 6869: 6865: 6863: 6859: 6855: 6851: 6847: 6843: 6839: 6835: 6831: 6827: 6825: 6821: 6817: 6813: 6809: 6805: 6801: 6797: 6795: 6791: 6788: 6786: 6782: 6776: 6773: 6771: 6768: 6766: 6763: 6760: 6756: 6753: 6749: 6746: 6744: 6743:Retrospective 6741: 6740: 6739: 6736: 6734: 6730: 6726: 6723: 6722: 6720: 6717: 6712: 6708: 6700: 6697: 6696: 6695: 6692: 6688: 6685: 6683: 6680: 6678: 6675: 6674: 6673: 6670: 6669: 6667: 6664: 6663:EBM I to II-1 6659: 6655: 6649: 6646: 6644: 6641: 6639: 6636: 6634: 6631: 6629: 6626: 6622: 6619: 6617: 6614: 6613: 6612: 6609: 6608: 6606: 6602: 6598: 6594: 6587: 6582: 6580: 6575: 6573: 6568: 6567: 6564: 6557: 6554: 6551: 6548: 6545: 6542: 6539: 6536: 6535: 6522: 6518: 6513: 6508: 6504: 6500: 6496: 6492: 6488: 6481: 6473: 6469: 6464: 6459: 6454: 6449: 6445: 6441: 6437: 6430: 6422: 6418: 6413: 6408: 6404: 6400: 6396: 6389: 6381: 6377: 6372: 6367: 6362: 6357: 6353: 6349: 6345: 6338: 6322: 6318: 6312: 6310: 6293: 6289: 6285: 6279: 6277: 6268: 6264: 6260: 6256: 6252: 6248: 6245:(4): 477–94. 6244: 6240: 6233: 6231: 6222: 6218: 6213: 6208: 6204: 6200: 6195: 6190: 6186: 6182: 6178: 6170: 6154: 6150: 6144: 6128: 6122: 6106: 6102: 6097: 6090: 6082: 6078: 6074: 6070: 6066: 6062: 6058: 6054: 6050: 6046: 6042: 6035: 6019: 6015: 6009: 6001: 5997: 5992: 5987: 5983: 5979: 5975: 5971: 5967: 5963: 5959: 5952: 5936: 5932: 5928: 5922: 5906: 5902: 5896: 5888: 5884: 5879: 5874: 5869: 5864: 5860: 5856: 5852: 5845: 5837: 5833: 5829: 5825: 5821: 5817: 5813: 5809: 5802: 5794: 5790: 5785: 5780: 5776: 5772: 5768: 5764: 5760: 5753: 5745: 5741: 5736: 5731: 5726: 5721: 5717: 5713: 5709: 5702: 5686: 5682: 5678: 5672: 5664: 5660: 5656: 5652: 5647: 5642: 5638: 5634: 5630: 5623: 5607: 5603: 5597: 5578: 5571: 5565: 5546: 5539: 5533: 5517: 5513: 5509: 5503: 5487: 5483: 5479: 5473: 5465: 5461: 5457: 5451: 5440: 5433: 5427: 5411: 5407: 5406:Common Dreams 5403: 5397: 5389: 5385: 5380: 5375: 5370: 5365: 5361: 5357: 5356:PLOS Medicine 5353: 5346: 5331: 5327: 5323: 5322: 5315: 5299: 5295: 5289: 5281: 5279:9781096489085 5275: 5271: 5265: 5249: 5245: 5241: 5235: 5219: 5215: 5214:ninds.nih.gov 5211: 5205: 5197: 5193: 5188: 5183: 5179: 5175: 5171: 5164: 5162: 5153: 5149: 5145: 5141: 5136: 5131: 5127: 5123: 5119: 5112: 5096: 5092: 5088: 5084: 5080: 5076: 5072: 5068: 5064: 5060: 5053: 5045: 5041: 5036: 5031: 5027: 5023: 5019: 5015: 5011: 5007: 5003: 4996: 4988: 4984: 4980: 4976: 4971: 4966: 4962: 4958: 4954: 4947: 4939: 4935: 4930: 4925: 4921: 4917: 4913: 4909: 4905: 4901: 4897: 4889: 4873: 4869: 4865: 4860: 4855: 4851: 4847: 4843: 4836: 4817: 4814:. June 2010. 4813: 4812: 4804: 4798: 4782: 4778: 4772: 4764: 4760: 4755: 4750: 4747:(4): 279–80. 4746: 4742: 4738: 4731: 4723: 4719: 4715: 4711: 4707: 4703: 4699: 4695: 4687: 4671: 4667: 4663: 4657: 4638: 4631: 4625: 4617: 4613: 4608: 4603: 4599: 4595: 4591: 4587: 4583: 4576: 4560: 4556: 4552: 4548: 4544: 4537: 4518: 4514: 4510: 4506: 4502: 4498: 4494: 4487: 4480: 4472: 4468: 4463: 4458: 4454: 4450: 4446: 4442: 4438: 4431: 4412: 4405: 4399: 4391: 4387: 4382: 4377: 4373: 4369: 4365: 4361: 4357: 4350: 4334: 4330: 4329: 4321: 4319: 4310: 4304: 4296: 4292: 4287: 4282: 4278: 4274: 4270: 4266: 4262: 4258: 4254: 4247: 4245: 4228: 4224: 4223:Med-Quest.org 4220: 4214: 4205: 4189: 4185: 4179: 4170: 4154: 4150: 4146: 4139: 4120: 4113: 4106: 4098: 4094: 4090: 4086: 4082: 4078: 4071: 4063: 4059: 4054: 4049: 4045: 4041: 4037: 4033: 4029: 4022: 4006: 4002: 3998: 3991: 3975: 3971: 3965: 3957: 3953: 3948: 3943: 3939: 3935: 3931: 3924: 3916: 3912: 3907: 3902: 3898: 3894: 3890: 3886: 3882: 3875: 3867: 3865:9781461327035 3861: 3857: 3850: 3842: 3838: 3834: 3828: 3826: 3824: 3807: 3803: 3799: 3793: 3782: 3778: 3771: 3765: 3749: 3745: 3738: 3731: 3730:public domain 3712: 3708: 3702: 3686: 3682: 3676: 3668: 3664: 3659: 3654: 3649: 3644: 3640: 3636: 3632: 3628: 3624: 3617: 3609: 3605: 3601: 3597: 3592: 3587: 3583: 3579: 3575: 3568: 3560: 3556: 3551: 3546: 3542: 3538: 3534: 3527: 3525: 3523: 3506: 3502: 3498: 3492: 3490: 3481: 3477: 3473: 3469: 3464: 3459: 3456:(9685): 176. 3455: 3451: 3447: 3440: 3432: 3426: 3422: 3421: 3413: 3397: 3393: 3386: 3370: 3366: 3360: 3344: 3340: 3333: 3325: 3321: 3316: 3311: 3307: 3303: 3299: 3292: 3276: 3272: 3266: 3264: 3255: 3251: 3246: 3241: 3236: 3231: 3227: 3223: 3219: 3212: 3205: 3201: 3198: 3192: 3184: 3180: 3176: 3172: 3168: 3164: 3160: 3156: 3149: 3133: 3129: 3126:Hani (2009). 3122: 3116: 3115:0-13-613550-1 3112: 3106: 3098: 3094: 3089: 3084: 3080: 3076: 3072: 3065: 3057: 3051: 3047: 3046: 3038: 3030: 3024: 3020: 3019: 3011: 2995: 2991: 2987: 2981: 2965: 2961: 2955: 2948: 2947:0-471-24410-4 2944: 2940: 2934: 2927: 2926:0-7432-2209-1 2923: 2919: 2913: 2907: 2906:0-312-31391-8 2903: 2899: 2893: 2885: 2879: 2875: 2871: 2867: 2866: 2858: 2842: 2838: 2832: 2828: 2827: 2819: 2817: 2815: 2813: 2797: 2793: 2787: 2772: 2768: 2762: 2754: 2750: 2745: 2740: 2735: 2730: 2726: 2722: 2718: 2711: 2703: 2699: 2694: 2689: 2685: 2681: 2677: 2673: 2669: 2662: 2654: 2650: 2646: 2642: 2638: 2634: 2631:(3): 409–16. 2630: 2626: 2619: 2611: 2607: 2602: 2597: 2593: 2589: 2585: 2581: 2577: 2570: 2562: 2558: 2553: 2548: 2544: 2540: 2536: 2529: 2513: 2509: 2503: 2497: 2493: 2489: 2485: 2484:Health Canada 2482:; in Canada, 2481: 2475: 2459: 2455: 2449: 2447: 2445: 2443: 2441: 2439: 2437: 2435: 2433: 2431: 2422: 2418: 2414: 2410: 2406: 2402: 2395: 2388: 2382: 2376: 2372: 2369: 2363: 2357: 2353: 2350: 2344: 2338: 2334: 2331: 2325: 2318: 2302: 2298: 2297: 2292: 2288: 2282: 2266: 2260: 2244: 2238: 2230: 2226: 2221: 2216: 2212: 2208: 2204: 2200: 2193: 2174: 2167: 2161: 2145: 2141: 2135: 2133: 2131: 2126: 2116: 2113: 2111: 2108: 2106: 2103: 2101: 2098: 2097: 2091: 2089: 2085: 2071: 2068: 2064: 2060: 2056: 2053: 2049: 2048: 2047: 2039: 2031: 2022: 2020: 2016: 2012: 2007: 2002: 1993: 1991: 1982: 1979: 1976: 1973: 1970: 1967: 1964: 1963: 1962: 1960: 1955: 1953: 1950:populations. 1949: 1940: 1936: 1932: 1923: 1914: 1908:Investigators 1905: 1903: 1899: 1895: 1890: 1884: 1881: 1878: 1875: 1872: 1869: 1866: 1863: 1860: 1857: 1856: 1855: 1848: 1840: 1824: 1815: 1813: 1807: 1803: 1795: 1791: 1787: 1782: 1778: 1768: 1764: 1762: 1758: 1748: 1744: 1740: 1736: 1734: 1733: 1721: 1718: 1710: 1707:November 2014 1700: 1696: 1692: 1686: 1685: 1681: 1676:This section 1674: 1670: 1665: 1664: 1656: 1653: 1648: 1645: 1644:adverse event 1641: 1636: 1632: 1628: 1617: 1613: 1611: 1607: 1601: 1592: 1589: 1582: 1578: 1564: 1561: 1558: 1555: 1552: 1549: 1546: 1545: 1543: 1541: 1530: 1527: 1522: 1520: 1516: 1510: 1506: 1504: 1499: 1498:translational 1493: 1491: 1487: 1475: 1471: 1461: 1459: 1458:business news 1453: 1451: 1447: 1442: 1440: 1436: 1432: 1427: 1424: 1422: 1417: 1415: 1410: 1405: 1403: 1399: 1392: 1388: 1378: 1375: 1369: 1359: 1352: 1348: 1344: 1340: 1335: 1331: 1327: 1322: 1318: 1308: 1299: 1291: 1289: 1283: 1276: 1272: 1264: 1253: 1251: 1246: 1244: 1243:skin diseases 1240: 1236: 1232: 1227: 1223: 1215: 1211: 1208: 1207: 1206: 1203: 1195: 1186: 1184: 1179: 1177: 1171: 1161: 1159: 1154: 1152: 1141: 1137: 1135: 1128: 1123: 1109: 1107: 1106: 1101: 1097: 1093: 1089: 1085: 1079: 1077: 1071: 1069: 1063: 1061: 1055: 1045: 1043: 1038: 1034: 1032: 1021: 1019: 1008: 1004: 997: 993: 989: 986: 985: 984: 983:-controlled. 982: 978: 973: 970: 968: 964: 960: 956: 952: 948: 940: 922: 905: 902: 899: 898: 893: 890: 887: 886: 881: 879: 878:control group 876: 872: 868: 865: 864: 860: 856: 853: 850: 849: 844: 841: 837: 834: 831: 830: 826: 823: 820: 819: 816: 815: 814: 811: 807: 799: 781: 771: 764: 759: 756: 753: 749: 745: 742: 739: 738: 734: 731: 730: 726: 723: 719: 718: 714: 711: 707: 704: 701: 698: 695: 692: 689: 685: 681: 677: 673: 669: 666: 665: 664: 662: 654: 650: 647: 643: 642: 641: 633: 631: 626: 623: 621: 613: 612:Royal Society 609: 605: 601: 597: 593: 589: 585: 581: 577: 572: 570: 566: 562: 558: 552: 550: 546: 541: 538: 534: 530: 526: 522: 518: 517:randomization 514: 510: 506: 503:Ideas of Sir 498: 494: 488:Modern trials 485: 483: 479: 475: 471: 467: 463: 459: 455: 453: 449: 448: 443: 439: 438:John Haygarth 434: 432: 428: 424: 420: 416: 415:sulfuric acid 412: 408: 403: 398: 396: 392: 388: 384: 380: 376: 372: 368: 363: 361: 357: 356:Edward Jenner 353: 349: 345: 341: 340:control group 333: 332:control group 329: 325: 324:Edward Jenner 321: 307: 305: 301: 297: 287: 285: 281: 277: 267: 265: 261: 257: 253: 249: 245: 235: 233: 229: 225: 221: 216: 214: 210: 205: 203: 198: 196: 188: 185: 182: 179: 176: 175: 174: 171: 169: 165: 159: 155: 153: 147: 143: 141: 126: 124: 120: 116: 115:biotechnology 112: 106: 104: 100: 96: 92: 88: 87:pilot studies 83: 81: 77: 73: 69: 65: 61: 57: 53: 49: 41: 37: 33: 19: 10755: 10743: 10724: 10717: 10629:Econometrics 10579: / 10562:Chemometrics 10539:Epidemiology 10532: / 10529: 10505:Applications 10347:ARIMA model 10294:Q-statistic 10243:Stationarity 10139:Multivariate 10082: / 10078: / 10076:Multivariate 10074: / 10014: / 10010: / 9784:Bayes factor 9683:Signed rank 9595: 9569: 9561: 9549: 9244:Completeness 9080:Cohort study 8978:Opinion poll 8913:Missing data 8900:Study design 8855:Scatter plot 8777:Scatter plot 8770:Spearman's ρ 8732:Grouped data 8419: 8380:Epidemiology 8356: 8328: 8214:DTaP-IPV/Hib 8005:Yellow fever 7918:EpiVacCorona 7670:Tuberculosis 7643:Pneumococcal 7611:Lyme disease 7439:Heterologous 7338:Immunization 7265:Wine tasting 7244: 7079: 7072: 7065: 6854:Hazard ratio 6738:Cohort study 6610: 6494: 6490: 6480: 6443: 6439: 6429: 6405:(1): 11–15. 6402: 6398: 6388: 6351: 6347: 6337: 6325:. Retrieved 6296:. Retrieved 6287: 6242: 6238: 6184: 6180: 6169: 6157:. Retrieved 6153:the original 6143: 6131:. Retrieved 6121: 6109:. Retrieved 6100: 6089: 6048: 6044: 6034: 6022:. Retrieved 6008: 5965: 5961: 5951: 5939:. Retrieved 5930: 5921: 5909:. Retrieved 5905:the original 5895: 5858: 5854: 5844: 5836:the original 5815: 5811: 5801: 5766: 5762: 5752: 5715: 5711: 5701: 5689:. Retrieved 5671: 5636: 5632: 5622: 5610:. Retrieved 5596: 5584:. Retrieved 5564: 5552:. Retrieved 5532: 5520:. Retrieved 5511: 5502: 5490:. Retrieved 5481: 5472: 5464:the original 5459: 5450: 5439:the original 5426: 5414:. Retrieved 5410:the original 5405: 5396: 5359: 5355: 5345: 5334:, retrieved 5320: 5314: 5302:. Retrieved 5288: 5269: 5264: 5252:. Retrieved 5243: 5234: 5222:. Retrieved 5218:the original 5213: 5204: 5177: 5173: 5125: 5121: 5111: 5099:. Retrieved 5066: 5062: 5052: 5012:(2): 95–97. 5009: 5005: 4995: 4960: 4956: 4946: 4903: 4899: 4888: 4876:. Retrieved 4852:(6): 786–8. 4849: 4845: 4835: 4823:. Retrieved 4809: 4797: 4785:. Retrieved 4771: 4744: 4740: 4730: 4697: 4693: 4686: 4674:. Retrieved 4665: 4656: 4644:. Retrieved 4637:the original 4624: 4589: 4585: 4575: 4563:. Retrieved 4546: 4536: 4524:. Retrieved 4496: 4492: 4479: 4444: 4440: 4430: 4418:. Retrieved 4411:the original 4398: 4363: 4359: 4349: 4337:. Retrieved 4327: 4303:cite journal 4260: 4256: 4231:. Retrieved 4227:the original 4222: 4213: 4204: 4192:. Retrieved 4188:the original 4178: 4169: 4157:. Retrieved 4148: 4138: 4126:. Retrieved 4119:the original 4105: 4083:(5): 565–9. 4080: 4076: 4070: 4035: 4031: 4021: 4009:. Retrieved 4000: 3990: 3978:. Retrieved 3974:the original 3964: 3940:(2): 39–41. 3937: 3933: 3923: 3888: 3884: 3874: 3855: 3849: 3841:the original 3836: 3810:. Retrieved 3801: 3792: 3781:the original 3776: 3764: 3752:. Retrieved 3748:the original 3737: 3715:. Retrieved 3710: 3701: 3689:. Retrieved 3675: 3630: 3626: 3616: 3581: 3577: 3567: 3543:(3): 211–7. 3540: 3536: 3509:. Retrieved 3500: 3453: 3449: 3439: 3419: 3412: 3400:. Retrieved 3396:the original 3385: 3373:. Retrieved 3359: 3347:. Retrieved 3332: 3305: 3301: 3291: 3279:. Retrieved 3225: 3221: 3211: 3191: 3158: 3154: 3148: 3136:. Retrieved 3132:the original 3121: 3105: 3081:(2): 212–7. 3078: 3075:Hypertension 3074: 3064: 3044: 3037: 3017: 3010: 2998:. Retrieved 2989: 2980: 2968:. Retrieved 2954: 2938: 2933: 2917: 2912: 2897: 2892: 2868:. New York: 2864: 2857: 2845:. Retrieved 2825: 2799:. Retrieved 2795: 2786: 2774:. Retrieved 2770: 2761: 2727:(1): 101–4. 2724: 2720: 2710: 2675: 2671: 2661: 2628: 2624: 2618: 2583: 2579: 2569: 2542: 2538: 2528: 2516:. Retrieved 2502: 2474: 2462:. Retrieved 2404: 2400: 2394: 2386: 2381: 2362: 2343: 2324: 2312: 2305:. Retrieved 2294: 2281: 2269:. Retrieved 2259: 2247:. Retrieved 2237: 2202: 2198: 2192: 2180:. Retrieved 2160: 2148:. Retrieved 2080: 2045: 2036: 2003: 1999: 1986: 1956: 1944: 1920: 1911: 1891: 1888: 1849: 1846: 1830: 1821: 1808: 1804: 1774: 1765: 1754: 1745: 1741: 1737: 1730: 1728: 1713: 1704: 1689:Please help 1677: 1649: 1623: 1614: 1602: 1598: 1584: 1550:Social value 1536: 1523: 1511: 1507: 1494: 1480:II and Phase 1467: 1454: 1443: 1428: 1425: 1418: 1406: 1394: 1371: 1314: 1305: 1297: 1284: 1259: 1247: 1228: 1224: 1220: 1204: 1200: 1180: 1173: 1155: 1147: 1138: 1131: 1103: 1080: 1072: 1064: 1057: 1035: 1027: 1014: 1005: 1001: 977:double-blind 974: 971: 963:cohort study 959:epidemiology 944: 915:Trial design 859:side effects 803: 769: 743: 735: 727: 715: 705: 699: 693: 667: 658: 652: 639: 627: 624: 588:Richard Doll 584:Karl Pearson 573: 565:double-blind 557:streptomycin 553: 548: 542: 537:interactions 512: 502: 456: 445: 435: 431:barley water 399: 395:citrus fruit 387:John Woodall 364: 337: 328:James Phipps 326:vaccinating 293: 280:subfertility 273: 241: 217: 206: 199: 192: 172: 160: 156: 148: 144: 137: 107: 84: 47: 46: 36: 10757:WikiProject 10672:Cartography 10634:Jurimetrics 10586:Reliability 10317:Time domain 10296:(Ljung–Box) 10218:Time-series 10096:Categorical 10080:Time-series 10072:Categorical 10007:(Bernoulli) 9842:Correlation 9822:Correlation 9618:Jarque–Bera 9590:Chi-squared 9352:M-estimator 9305:Asymptotics 9249:Sufficiency 9016:Interaction 8928:Replication 8908:Effect size 8865:Violin plot 8845:Radar chart 8825:Forest plot 8815:Correlogram 8765:Kendall's τ 8416:from market 8312:Controversy 8246:researchers 8162:Hepatitis B 8048:Hepatitis C 7993:Chicken pox 7819:Hepatitis E 7814:Hepatitis B 7809:Hepatitis A 7755:Chikungunya 7732:Shigellosis 7586:Brucellosis 7472:Therapeutic 7426:Inactivated 7366:Development 7354:Inoculation 7346:Vaccination 7209:Test method 7048:Null result 7007:Replication 6902:Infectivity 6824:Association 6775:Case report 6765:Case series 6748:Prospective 6327:26 December 6298:26 December 6159:14 November 6133:14 November 6111:26 February 5911:26 November 5612:11 November 5586:11 November 5554:11 November 5522:11 November 5492:11 November 5460:www.ich.org 5416:16 December 5336:16 December 5254:25 November 5224:25 November 4878:27 February 4420:19 November 4194:14 November 3980:14 November 3777:www.ich.org 3754:14 November 3711:www.fda.gov 3161:(1): 10–4. 2970:9 September 2307:26 February 2220:10161/12742 1474:US Congress 1096:South Korea 949:is between 596:lung cancer 559:for curing 525:uncertainty 523:—to reduce 521:replication 348:inoculation 315:Development 164:vital signs 10773:Categories 10624:Demography 10342:ARMA model 10147:Regression 9724:(Friedman) 9685:(Wilcoxon) 9623:Normality 9613:Lilliefors 9560:Student's 9436:Resampling 9310:Robustness 9298:divergence 9288:Efficiency 9226:(monotone) 9221:Likelihood 9138:Population 8971:Stratified 8923:Population 8742:Dependence 8698:Count data 8629:Percentile 8606:Dispersion 8539:Arithmetic 8474:Statistics 8347:Thiomersal 8293:Paul Offit 8268:Jonas Salk 8244:Inventors/ 8115:research: 8092:research: 8029:research: 7958:Skycovione 7948:Sanofi–GSK 7893:SARS-CoV-2 7804:Hantavirus 7765:rVSV-ZEBOV 7750:Adenovirus 7718:research: 7596:Diphtheria 7434:Attenuated 7240:Crash test 6850:Odds ratio 6842:Risk ratio 6808:Prevalence 6794:Occurrence 6770:Case study 6354:(1): 101. 6288:Cancer.Net 5941:9 December 4825:16 October 4339:7 November 4263:(1): 1–7. 4159:26 January 4011:26 January 3691:31 October 3138:27 October 2872:. p. 2870:Free Press 2287:Emanuel EJ 2150:7 November 2121:References 2084:telehealth 2051:databases. 1939:volunteers 1894:tax credit 1759:(IRB), or 1627:monitoring 1575:See also: 1450:pediatrics 1414:California 1366:See also: 1328:(EDC) and 746:trials or 700:Diagnostic 668:Prevention 580:statistics 367:James Lind 209:hypotheses 10005:Logistic 9772:posterior 9698:Rank sum 9446:Jackknife 9441:Bootstrap 9259:Bootstrap 9194:Parameter 9143:Statistic 8938:Statistic 8850:Run chart 8835:Pie chart 8830:Histogram 8820:Fan chart 8795:Bar chart 8677:L-moments 8564:Geometric 8426:Phase III 8414:Withdrawn 8342:Pox party 8152:ALVAC-CEA 8074:Protozoan 7963:Sputnik V 7913:CoronaVac 7883:Rotavirus 7781:Pandemrix 7633:Pertussis 7574:Bacterial 7458:Synthetic 7421:Conjugate 7373:Adjuvants 7350:Infection 6910:Morbidity 6898:Virulence 6800:Incidence 6203:2397-768X 6187:(1): 69. 6081:233351877 6065:2168-6181 5982:0091-6765 5812:Pharm Med 5718:(1): e5. 5144:1469-5111 5083:1399-5618 5026:1469-5111 4979:1469-5111 4920:1942-5546 4555:0362-4331 4277:1939-067X 3812:5 October 3511:10 August 3402:4 January 3375:4 January 3349:5 January 3302:Pharm Med 3228:: g7092. 2801:3 January 2776:3 January 2518:2 October 2486:; in the 2205:: 20–33. 2182:1 January 1827:Economics 1678:does not 1635:unblinded 1302:Marketing 1239:influenza 888:Phase III 842:in humans 706:Treatment 694:Screening 688:lifestyle 678:or other 470:nephritis 375:Vitamin C 358:over his 220:biologics 10719:Category 10412:Survival 10289:Johansen 10012:Binomial 9967:Isotonic 9554:(normal) 9199:location 9006:Blocking 8961:Sampling 8840:Q–Q plot 8805:Box plot 8787:Graphics 8682:Skewness 8672:Kurtosis 8644:Variance 8574:Heronian 8569:Harmonic 8184:Prostvac 8177:Gardasil 8172:Cervarix 8119:Hookworm 7998:Shingles 7980:Smallpox 7898:Corbevax 7834:Gardasil 7829:Cervarix 7567:Vaccines 7521:Schedule 7492:Global: 7400:Timeline 7342:Vaccines 7074:Glossary 7067:Category 6944:In vitro 6785:Measures 6604:Overview 6521:33997523 6472:36590004 6421:37851508 6380:36045401 6321:Archived 6292:Archived 6259:22376222 6221:36202909 6105:Archived 6073:33885733 6018:Archived 6000:26625444 5935:Archived 5887:16603070 5832:19557355 5793:21146635 5744:15829477 5691:27 March 5685:Archived 5663:24308679 5655:26908540 5606:Archived 5577:Archived 5545:Archived 5516:Archived 5486:Archived 5484:. 2005. 5388:22719228 5330:archived 5304:9 August 5298:Archived 5248:Archived 5196:32212920 5152:23672957 5095:Archived 5091:29327798 5044:28927197 4987:23672957 4938:22560521 4872:Archived 4868:11584570 4816:Archived 4781:Archived 4763:18711161 4714:21473670 4670:Archived 4616:12775622 4565:23 April 4559:Archived 4517:Archived 4513:71853867 4471:25391940 4390:17849641 4333:Archived 4295:21423790 4153:Archived 4128:26 April 4097:18755376 4062:27249699 4005:Archived 3956:22102925 3915:20585913 3806:Archived 3685:Archived 3667:26978655 3627:PLOS ONE 3608:19333613 3600:26378704 3559:19463302 3505:Archived 3480:30939770 3472:19616703 3369:Archived 3343:Archived 3324:31439802 3275:Archived 3254:25516539 3200:Archived 3183:39878743 3175:21350072 2994:Archived 2964:Archived 2962:. 2001. 2841:Archived 2753:27019801 2702:31995657 2653:17084906 2645:20142732 2610:25517397 2561:19826022 2512:Archived 2458:Archived 2421:17374817 2371:Archived 2352:Archived 2333:Archived 2301:Archived 2229:26928437 2173:Archived 2144:Archived 2094:See also 2042:Matching 2025:Research 1917:Subjects 1588:HIV/AIDS 1362:Analysis 1189:Duration 1176:randomly 1018:labeling 965:and the 900:Phase IV 866:Phase II 690:changes. 684:vaccines 676:vitamins 529:blocking 425:and one 352:smallpox 276:fibroids 129:Overview 56:vaccines 10745:Commons 10692:Kriging 10577:Process 10534:studies 10393:Wavelet 10226:General 9393:Plug-in 9187:L space 8966:Cluster 8667:Moments 8485:Outline 8373:Related 8319:General 8081:Malaria 7968:Valneva 7933:Novavax 7928:Moderna 7923:Janssen 7908:CanSino 7888:Rubella 7846:Measles 7712:Td/Tdap 7682:Typhoid 7665:Tetanus 7660:Q fever 7591:Cholera 7581:Anthrax 7450:Peptide 7414:Classes 7395:Storage 7281:Hedonic 6949:In vivo 6512:8093545 6463:9797802 6371:9428375 6267:1344880 6212:9537311 6024:7 April 5991:4670264 5878:1475627 5784:4943215 5735:1550630 5512:fda.gov 5379:3373653 5035:5356994 4929:3538468 4722:2583905 4607:1126054 4526:13 July 4449:Bibcode 4381:9527709 4286:3059317 4053:5495113 3947:3218552 3906:3018227 3802:ich.org 3717:25 July 3658:4792418 3635:Bibcode 3245:4267482 3097:1737655 3000:7 April 2928:. p. 7. 2744:4804244 2693:6989141 2601:7061494 2271:9 March 2249:9 March 1843:Sponsor 1699:removed 1684:sources 1620:Sponsor 1294:Quality 981:placebo 875:placebo 851:Phase I 832:Phase 0 729:Genetic 592:smoking 423:oranges 419:vinegar 411:vitriol 310:History 195:placebo 10614:Census 10204:Normal 10152:Manova 9972:Robust 9722:2-way 9714:1-way 9552:-test 9223: 8800:Biplot 8591:Median 8584:Lehmer 8526:Center 8409:WHO-EM 8329:Lancet 8206:TA-NIC 8191:NicVAX 8038:Dengue 7878:Rabies 7699:Typhus 7638:Plague 7516:Policy 7477:Toxoid 7405:Trials 7292:Likert 7274:Scales 6519: 6509: 6470: 6460: 6419: 6399:Cancer 6378: 6368: 6265: 6257: 6219: 6209: 6201: 6079: 6071: 6063: 5998: 5988: 5980: 5885: 5875: 5855:Trials 5830: 5791: 5781: 5742: 5732: 5661: 5653: 5386: 5376: 5276: 5194: 5150: 5142: 5101:27 May 5089: 5081: 5042: 5032: 5024: 4985: 4977: 4936: 4926: 4918: 4866: 4856: 4787:22 May 4761: 4720: 4712: 4676:22 May 4646:2 June 4614: 4604: 4553: 4511: 4469: 4441:Nature 4388: 4378: 4293: 4283: 4275: 4233:20 May 4095: 4060: 4050: 3954: 3944: 3913: 3903: 3862: 3665: 3655: 3606: 3598: 3557: 3478: 3470: 3450:Lancet 3427: 3322: 3281:24 May 3252: 3242: 3181: 3173: 3113: 3095: 3052: 3025: 2945: 2924: 2904: 2880: 2847:5 June 2833: 2751: 2741: 2700: 2690: 2651: 2643: 2608: 2598: 2559: 2490:, the 2464:24 May 2419: 2315: 2227: 1852: 1837: 1833: 1799: 1790:510(k) 1595:Safety 1482: 1478: 1355: 1279: 1267: 1241:, and 1217:trial. 1213:years. 1105:Trials 1100:the UK 1098:, and 1088:Canada 979:, and 827:Notes 810:decade 774:Phases 651:In an 644:In an 616: 466:London 371:scurvy 70:, and 10238:Trend 9767:prior 9709:anova 9598:-test 9572:-test 9564:-test 9471:Power 9416:Pivot 9209:shape 9204:scale 8654:Shape 8634:Range 8579:Heinz 8554:Cubic 8490:Index 8337:NCVIA 8201:TA-CD 8135:Other 8086:RTS,S 7866:Sabin 7861:Polio 7856:Mumps 7760:Ebola 7743:Viral 7692:ViCPS 7687:Ty21a 7621:MeNZB 7551:VAERS 7501:NITAG 7430:Live 7288:(JAR) 6888:Other 6263:S2CID 6077:S2CID 5931:NIMHD 5861:: 9. 5828:S2CID 5659:S2CID 5580:(PDF) 5573:(PDF) 5548:(PDF) 5541:(PDF) 5442:(PDF) 5435:(PDF) 4859:81460 4819:(PDF) 4806:(PDF) 4718:S2CID 4640:(PDF) 4633:(PDF) 4520:(PDF) 4509:S2CID 4489:(PDF) 4414:(PDF) 4407:(PDF) 4122:(PDF) 4115:(PDF) 3784:(PDF) 3773:(PDF) 3604:S2CID 3476:S2CID 3320:S2CID 3179:S2CID 2649:S2CID 2176:(PDF) 2169:(PDF) 1961:for: 1781:audit 1526:Tohen 1421:HIPAA 1158:lipid 1151:power 1092:China 821:Phase 686:, or 672:drugs 636:Types 472:with 427:lemon 407:cider 379:Anson 152:fetus 60:drugs 10471:Test 9671:Sign 9523:Wald 8596:Mode 8534:Mean 8063:Zika 8023:MMRV 7871:Salk 7851:Mpox 7797:LAIV 7792:H5N8 7787:H5N1 7777:H1N1 7653:PPSV 7536:ACIP 7532:US: 7506:SAGE 7467:mRNA 7383:list 6727:vs. 6595:and 6517:PMID 6468:PMID 6417:PMID 6376:PMID 6329:2023 6300:2023 6255:PMID 6217:PMID 6199:ISSN 6161:2013 6135:2013 6113:2019 6069:PMID 6061:ISSN 6026:2023 5996:PMID 5978:ISSN 5943:2022 5913:2016 5883:PMID 5789:PMID 5740:PMID 5693:2007 5651:PMID 5614:2017 5588:2017 5556:2017 5524:2017 5494:2017 5418:2007 5384:PMID 5338:2019 5306:2017 5274:ISBN 5256:2019 5226:2019 5192:PMID 5148:PMID 5140:ISSN 5103:2021 5087:PMID 5079:ISSN 5040:PMID 5022:ISSN 4983:PMID 4975:ISSN 4934:PMID 4916:ISSN 4880:2011 4864:PMID 4846:CMAJ 4827:2014 4789:2018 4759:PMID 4710:PMID 4678:2018 4648:2008 4612:PMID 4567:2020 4551:ISSN 4528:2019 4467:PMID 4422:2007 4386:PMID 4341:2022 4309:link 4291:PMID 4273:ISSN 4235:2015 4196:2013 4161:2020 4130:2010 4093:PMID 4058:PMID 4013:2020 3982:2013 3952:PMID 3911:PMID 3860:ISBN 3814:2008 3756:2013 3719:2024 3693:2017 3663:PMID 3596:PMID 3555:PMID 3513:2020 3468:PMID 3425:ISBN 3404:2014 3377:2014 3351:2014 3283:2019 3250:PMID 3171:PMID 3140:2011 3111:ISBN 3093:PMID 3050:ISBN 3023:ISBN 3002:2023 2972:2007 2943:ISBN 2922:ISBN 2902:ISBN 2878:ISBN 2849:2020 2831:ISBN 2803:2024 2778:2024 2749:PMID 2698:PMID 2676:2020 2641:PMID 2606:PMID 2584:2014 2557:PMID 2539:JAMA 2520:2017 2466:2019 2417:PMID 2401:JAMA 2309:2017 2273:2024 2251:2024 2225:PMID 2184:2014 2152:2022 2086:and 2017:and 1810:the 1797:"... 1779:can 1682:any 1680:cite 1579:and 1389:and 1343:ePRO 953:and 838:and 594:and 567:and 543:The 278:for 101:and 9651:BIC 9646:AIC 8324:MMR 8167:HPV 8157:BCG 8058:HIV 8018:MMR 7824:HPV 7772:Flu 7675:BCG 7648:PCV 7601:Hib 7556:VSD 7463:DNA 7358:J07 6507:PMC 6499:doi 6458:PMC 6448:doi 6407:doi 6403:130 6366:PMC 6356:doi 6247:doi 6207:PMC 6189:doi 6053:doi 6049:147 5986:PMC 5970:doi 5966:123 5873:PMC 5863:doi 5820:doi 5779:PMC 5771:doi 5730:PMC 5720:doi 5641:doi 5374:PMC 5364:doi 5182:doi 5130:doi 5071:doi 5030:PMC 5014:doi 4965:doi 4924:PMC 4908:doi 4854:PMC 4850:165 4749:doi 4745:149 4702:doi 4602:PMC 4594:doi 4590:326 4501:doi 4457:doi 4445:515 4376:PMC 4368:doi 4281:PMC 4265:doi 4085:doi 4048:PMC 4040:doi 3942:PMC 3901:PMC 3893:doi 3889:469 3653:PMC 3643:doi 3586:doi 3582:121 3545:doi 3458:doi 3454:374 3310:doi 3240:PMC 3230:doi 3226:349 3222:BMJ 3163:doi 3083:doi 2739:PMC 2729:doi 2688:PMC 2680:doi 2633:doi 2629:251 2596:PMC 2588:doi 2547:doi 2543:302 2409:doi 2405:297 2317:... 2215:hdl 2207:doi 2065:or 1788:or 1786:NDA 1777:FDA 1693:by 1252:). 1078:). 824:Aim 622:." 464:in 381:'s 10775:: 8422:: 7465:/ 7456:/ 7452:/ 7448:/ 7352:, 7348:, 7344:, 7340:: 7336:/ 6924:, 6920:, 6916:, 6912:, 6908:, 6904:, 6900:, 6896:, 6878:, 6874:, 6870:, 6852:, 6848:, 6844:, 6840:, 6836:, 6832:, 6814:, 6810:, 6806:, 6802:, 6731:, 6515:. 6505:. 6493:. 6489:. 6466:. 6456:. 6446:. 6444:10 6442:. 6438:. 6415:. 6401:. 6397:. 6374:. 6364:. 6352:14 6350:. 6346:. 6308:^ 6286:. 6275:^ 6261:. 6253:. 6243:17 6241:. 6229:^ 6215:. 6205:. 6197:. 6183:. 6179:. 6099:. 6075:. 6067:. 6059:. 6047:. 6043:. 5994:. 5984:. 5976:. 5964:. 5960:. 5933:. 5929:. 5881:. 5871:. 5857:. 5853:. 5826:. 5816:25 5814:. 5810:. 5787:. 5777:. 5767:32 5765:. 5761:. 5738:. 5728:. 5714:. 5710:. 5679:. 5657:. 5649:. 5637:13 5635:. 5631:. 5510:. 5480:. 5458:. 5404:. 5382:. 5372:. 5358:. 5354:. 5324:, 5242:. 5212:. 5190:. 5176:. 5172:. 5160:^ 5146:. 5138:. 5126:16 5124:. 5120:. 5093:. 5085:. 5077:. 5067:20 5065:. 5061:. 5038:. 5028:. 5020:. 5010:20 5008:. 5004:. 4981:. 4973:. 4961:16 4959:. 4955:. 4932:. 4922:. 4914:. 4904:87 4902:. 4898:. 4870:. 4862:. 4848:. 4844:. 4808:. 4757:. 4743:. 4739:. 4716:. 4708:. 4698:27 4696:. 4664:. 4610:. 4600:. 4588:. 4584:. 4557:. 4549:. 4545:. 4515:. 4507:. 4497:12 4495:. 4491:. 4465:. 4455:. 4443:. 4439:. 4384:. 4374:. 4364:13 4362:. 4358:. 4317:^ 4305:}} 4301:{{ 4289:. 4279:. 4259:. 4255:. 4243:^ 4221:. 4147:. 4091:. 4081:26 4079:. 4056:. 4046:. 4036:35 4034:. 4030:. 3999:. 3950:. 3936:. 3932:. 3909:. 3899:. 3887:. 3883:. 3835:. 3822:^ 3804:. 3800:. 3775:. 3709:. 3661:. 3651:. 3641:. 3631:11 3629:. 3625:. 3602:. 3594:. 3580:. 3576:. 3553:. 3539:. 3535:. 3521:^ 3503:. 3499:. 3488:^ 3474:. 3466:. 3452:. 3448:. 3318:. 3306:24 3304:. 3300:. 3262:^ 3248:. 3238:. 3224:. 3220:. 3177:. 3169:. 3159:19 3157:. 3091:. 3079:19 3077:. 3073:. 2992:. 2988:. 2876:. 2874:31 2839:. 2811:^ 2794:. 2769:. 2747:. 2737:. 2723:. 2719:. 2696:. 2686:. 2674:. 2670:. 2647:. 2639:. 2627:. 2604:. 2594:. 2582:. 2578:. 2555:. 2541:. 2537:. 2429:^ 2415:. 2403:. 2311:. 2299:. 2293:. 2223:. 2213:. 2203:47 2201:. 2129:^ 2090:. 2061:, 1992:. 1492:. 1460:. 1237:, 1233:, 1094:, 1090:, 1070:. 1058:A 1020:. 861:. 682:, 674:, 571:. 266:. 226:, 222:, 197:. 170:. 154:. 125:. 113:, 66:, 62:, 58:, 9596:G 9570:F 9562:t 9550:Z 9269:V 9264:U 8466:e 8459:t 8452:v 8333:) 8326:( 7783:) 7779:( 7360:) 7356:( 7326:e 7319:t 7312:v 7116:e 7109:t 7102:v 6761:) 6757:( 6718:) 6714:( 6665:) 6661:( 6585:e 6578:t 6571:v 6523:. 6501:: 6495:6 6474:. 6450:: 6423:. 6409:: 6382:. 6358:: 6331:. 6302:. 6269:. 6249:: 6223:. 6191:: 6185:6 6163:. 6137:. 6115:. 6083:. 6055:: 6028:. 6002:. 5972:: 5945:. 5915:. 5889:. 5865:: 5859:7 5822:: 5795:. 5773:: 5746:. 5722:: 5716:7 5695:. 5665:. 5643:: 5616:. 5590:. 5558:. 5526:. 5496:. 5420:. 5390:. 5366:: 5360:9 5308:. 5282:. 5258:. 5228:. 5198:. 5184:: 5178:7 5154:. 5132:: 5105:. 5073:: 5046:. 5016:: 4989:. 4967:: 4940:. 4910:: 4882:. 4829:. 4791:. 4765:. 4751:: 4724:. 4704:: 4680:. 4650:. 4618:. 4596:: 4569:. 4530:. 4503:: 4473:. 4459:: 4451:: 4424:. 4392:. 4370:: 4343:. 4311:) 4297:. 4267:: 4261:3 4237:. 4198:. 4163:. 4132:. 4099:. 4087:: 4064:. 4042:: 4015:. 3984:. 3958:. 3938:4 3917:. 3895:: 3868:. 3816:. 3758:. 3732:. 3721:. 3695:. 3669:. 3645:: 3637:: 3610:. 3588:: 3561:. 3547:: 3541:1 3515:. 3482:. 3460:: 3433:. 3406:. 3379:. 3353:. 3326:. 3312:: 3285:. 3256:. 3232:: 3185:. 3165:: 3142:. 3099:. 3085:: 3058:. 3031:. 3004:. 2974:. 2949:. 2886:. 2851:. 2805:. 2780:. 2755:. 2731:: 2725:6 2704:. 2682:: 2655:. 2635:: 2612:. 2590:: 2563:. 2549:: 2522:. 2468:. 2423:. 2411:: 2275:. 2253:. 2231:. 2217:: 2209:: 2186:. 2154:. 1990:s 1720:) 1714:( 1709:) 1705:( 1701:. 1687:. 1448:( 1149:" 998:. 724:. 712:. 413:( 334:. 34:. 20:)

Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.