346:, however, where each subject undergoes both treatments in succession, the natural history of the chronic condition under investigation (e.g., progression) is well understood, with the study's duration being chosen such that the condition's intensity will be more or less stable over that duration. (Wang et al. provide the example of late-phase diabetes, whose natural history is long enough that even a crossover study lasting one year is acceptable.) In these circumstances, a natural history group is not expected to yield useful information.
661:", and 2 were "sub-acute". He then compared the results of his dummy "placeboic remedy" with that of the active treatment's already well-understood results. (Flint had previously tested, and reported on, the active treatment's efficacy.) There was no significant difference between the results of the active treatment and his "placeboic remedy" in 12 of the cases in terms of disease duration, duration of convalescence, number of joints affected, and emergence of
634:(1812–1886) conducted the first-ever trial that directly compared the efficacy of a dummy simulator with that of an active treatment; although Flint's examination did not compare the two against each other in the same trial. Even so, this was a significant departure from the (then) customary practice of contrasting the consequences of an active treatment with what Flint described as "the natural history of disease".
492:
33:
104:, that is, effects from treatment that do not depend on the treatment itself. Such factors include knowing one is receiving a treatment, attention from health care professionals, and the expectations of a treatment's effectiveness by those running the research study. Without a placebo group to compare against, it is not possible to know whether the treatment itself had any effect.
75:
1063:, which specifically limited its directives to health research by physicians, and emphasized a number of additional conditions in circumstances where "medical research is combined with medical care". The significant difference between the 1947 Nuremberg Code and the 1964 Declaration of Helsinki is that the first was a set of principles that was
191:, and others. A blind can be imposed on any participant of an experiment, including subjects, researchers, technicians, data analysts, and evaluators. In some cases, while blinding would be useful, it is impossible or unethical. For example, is not possible to blind a patient to their treatment in a physical therapy intervention. A good
1147:" that contained a range of contributions to this question. As the abstract of one paper noted: "Unlike within the domain of medicine, in which the logic of placebos is relatively straightforward, the concept of placebo as applied to psychotherapy is fraught with both conceptual and practical problems."
1093:
The WMA hereby reaffirms its position that extreme care must be taken in making use of a placebo-controlled trial and that in general this methodology should only be used in the absence of existing proven therapy. However, a placebo-controlled trial may be ethically acceptable, even if proven therapy
1081:
29. The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods. This does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic method
789:
Each time a subject had a headache, they took their group's designated test drug, and recorded whether their headache had been relieved (or not). Although "some subjects had only three headaches in the course of a two-week period while others had up to ten attacks in the same period", the data showed
910:
made a significant contribution to the remedy's efficacy. Examining his data, Jellinek discovered that there was a very significant difference in responses between the 120 placebo-responders and the 79 non-responders. The 79 non-responders' reports showed that if they were considered as an entirely
1004:, because those admitting each patient knew to which group that patient would be allocated (and so the decision to admit or not admit a specific patient might be influenced by the experimenter's knowledge of the nature of their illness, and their knowledge of the group to which they would occupy).
354:
In certain clinical trials of particular drugs, it may happen that the level of the "placebo responses" manifested by the trial's subjects are either considerably higher or lower (in relation to the "active" drug's effects) than one would expect from other trials of similar drugs. In these cases,
202:
if they deduce or otherwise obtain information that has been masked to them. Unblinding that occurs before the conclusion of a study is a source of experimental error, as the bias that was eliminated by blinding is re-introduced. Unblinding is common in blind experiments, and must be measured and
124:
researcher wrote, "the first object of a therapeutic trial is to discover whether the patients who receive the treatment under investigation are cured more rapidly, more completely or more frequently, than they would have been without it." More broadly, the aim of a clinical trial is to determine
1138:
by clinical trial. However, there is controversy over what might or might not be an appropriate placebo for such therapeutic treatments. Furthermore, there are methodological challenges such as blinding the person providing the psychological non-drug intervention. In 2005, the
1007:
Recently, an earlier MRC trial on the antibiotic patulin on the course of common colds has been suggested to have been the first randomized trial. Another early and until recently overlooked randomized trial was published on strophanthin in a local
Finnish journal in 1946.
408:
The
Coronary Drug Project was intended to study the safety and effectiveness of drugs for long-term treatment of coronary heart disease in men. Those in the placebo group who adhered to the placebo treatment (took the placebo regularly as instructed) showed nearly half the
152:
type. Government regulatory agencies approve new drugs only after tests establish not only that patients respond to them, but also that their effect is greater than that of a placebo (by way of affecting more patients, by affecting responders more strongly, or both).
120:, many patients will get better even when given no treatment at all. Thus, the relevant question when assessing a treatment is not "does the treatment work?" but "does the treatment work better than a placebo treatment, or no treatment at all?" As one early
999:
What made this trial novel was that the subjects were randomly allocated to their test groups. The up-to-that-time practice was to allocate subjects alternately to each group, based on the order in which they presented for treatment. This practice could be
111:
treatments can take many forms, such as a pill containing only sugar, a surgery where nothing efficacious is actually done (just an incision and sometimes some minor touching or handling of the underlying structures), or a medical device (such as an
439:
In some cases, a study participant may deduce or otherwise obtain information that has been blinded to them. For example, a patient taking a psychoactive drug may recognize that they are taking a drug. When this occurs, it is called
1109:
In addition to the requirement for informed consent from all drug-trial participants, it is also standard practice to inform all test subjects that they may receive the drug being tested or that they may receive the placebo.
581:
He noted that the pair who had been given the oranges and lemons were so restored to health within six days of treatment that one of them returned to duty, and the other was well enough to attend the rest of the sick.
1101:— Where a prophylactic, diagnostic or therapeutic method is being investigated for a minor condition and the patients who receive placebo will not be subject to any additional risk of serious or irreversible harm.
394:
However, in particular cases such as the use of
Cimetidine to treat ulcers, a significant level of placebo response can also prove to be an index of how much the treatment has been directed at a wrong target.
413:
as those who were not adherent. A similar study of women similarly found survival was nearly 2.5 times greater for those who adhered to their placebo. This apparent placebo effect may have occurred because:
528:
Treatise on the Scurvy in Three Parts
Containing an Inquiry into the Nature, Causes, and Cure of the Disease, Together with a Critical and Chronological View of what has been Published of the Subject
790:
a "great consistency" across all subjects Every two weeks the groups' drugs were changed; so that by the end of eight weeks, all groups had tested all the drugs. The stipulated drug (i.e.,
641:... to secure the moral effect of a remedy given specially for the disease, the patients were placed on the use of a placebo which consisted, in nearly all of the cases, of the tincture of
175:
Blinding is the withholding of information from participants which may influence them in some way until after the experiment is complete. Good blinding may reduce or eliminate experimental
97:
trials, where subjects do not know whether they are receiving real or placebo treatment. Often, there is also a further "natural history" group that does not receive any treatment at all.
724:". (Note that the trial conducted by Austin Flint is an example of such a drug efficacy vs. placebo efficacy trial.) The four test drugs were identical in shape, size, colour and taste:
1098:— Where for compelling and scientifically sound methodological reasons its use is necessary to determine the efficacy or safety of a prophylactic, diagnostic or therapeutic method; or
223:, equally matched trial groups, Reilly wrote: "... it is necessary to remember the adjective 'random' should apply to the method of drawing the sample and not to the sample itself."
2130:
526:. He randomly divided twelve scurvy patients, whose "cases were as similar as I could have them", into six pairs. Each pair was given a different remedy. According to Lind's 1753
1020:
questions of the ethics of medical practice have been widely discussed, and codes of practice have been gradually developed as a response to advances in scientific medicine. The
923:: viz., 88%, 67%, and 77%, respectively. And because this significant difference in relief from the test drugs could only be attributed to the presence or absence of ingredient
1817:
944:") or "true physiological headaches accessible to suggestion". Thus, according to this view, the degree to which a "placebo response" is present tends to be an index of the
1819:
Of the
Imagination, as a Cause and as a Cure of Disorders of the Body; Exemplified by Fictitious Tractors, and Epidemical Convulsions (New Edition, with Additional Remarks)
955:
to that particular placebo may be responding for a wide number of reasons unconnected with the drug's active ingredients; and, from this, it could be important to pre-
2031:
1433:
Wang T, Malone J, Fu H, Heilmann C, Qu Y, Huster WJ. Crossover design and its application in late-phase diabetes studies. J Diabetes. 2016 Sep;8(5):610-8. PubMed ID:
1856:
Flint, A., "A Contribution Toward the
Natural History of Articular Rheumatism, Consisting of a Report of Thirteen Cases Treated Solely with Palliative Measures",
1446:
Coronary Drug
Project Research Group (October 1980). "Influence of adherence to treatment and response of cholesterol on mortality in the coronary drug project".
1367:
Di Blasi, Zelda; Harkness, Elaine; Edzard, Ernst; Georgiou, Amanda; Kleijnen, Jos (2019). "Influence of context effects on health outcomes: a systematic review".
938:
Jellinek, having identified 120 "placebo reactors", went on to suppose that all of them may have had either "psychological headaches" (with or without attendant "
1481:
Gallagher, E. J.; Viscoli, C. M.; Horwitz, R. I. (1993). "The relationship of treatment adherence to the risk of death after myocardial infarction in women".
1863:
156:
This close association of placebo effects with RCTs has a profound impact on how placebo effects are understood and valued in the scientific community.
2267:
2090:"Commentary: the 1944 patulin trial: the first properly controlled multicentre trial conducted under the aegis of the British Medical Research Council"
2202:
Herbert James D (2005). "Moving from empirically supported treatment lists to practice guidelines in psychotherapy: The role of the placebo concept".
685:
Jellinek in 1946 was asked to test whether or not the headache drug's overall efficacy would be reduced if certain ingredients were removed. In post-
959:
potential test populations, and treat those manifesting a placebo-response as a special group, or remove them altogether from the test population!
471:, a substance that produces noticeable physical effects intended to lead the control subjects to believe they had received the psychoactive drug.
1332:
Lohr JM, Olatunji BO, Parker L, DeMaio C (July 2005). "Experimental analysis of specific treatment factors: efficacy and practice implications".
448:, which is a drug that produces effects similar to the active drug, making it more difficult for patients to determine which group they are in.
85:
are a way of testing a medical therapy in which, in addition to a group of subjects that receives the treatment to be evaluated, a separate
2134:
1105:
All other provisions of the
Declaration of Helsinki must be adhered to, especially the need for appropriate ethical and scientific review.
637:
Flint's paper is the first time that he terms "placebo" or "placeboic remedy" were used to refer to a dummy simulator in a clinical trial.
342:
Natural-History groups yield useful information when separate groups of subjects are used in a parallel or longitudinal study design. In
1516:
Harman WW, McKim RH, Mogar RE, Fadiman J, Stolaroff MJ (August 1966). "Psychedelic agents in creative problem-solving: a pilot study".
17:
880:
Over the entire population of 199 subjects, there were 120 "subjects reacting to placebo" and 79 "subjects not reacting to placebo".
50:
1826:
689:
1946, pharmaceutical chemicals were restricted, and one U.S. headache remedy manufacturer sold a drug composed of three ingredients:
2559:
2555:
2605:
2563:
2551:
2260:
42:
1942:"Use of randomisation in the Medical Research Council's clinical trial of streptomycin in pulmonary tuberculosis in the 1940s"
1624:
2726:
2642:
2028:
1212:
591:
806:) was taken as often as necessary over each two-week period, and the two-week sequences for each of the four groups were:
2507:
2477:
2239:
594:, comparing the effects of allegedly "magnetized" water with that of plain water. It did not examine the practices of
2253:
665:. In the thirteenth case, Flint expressed some doubt whether the particular complications that had emerged (namely,
2764:
722:
was to express the efficacy or non-efficacy of a drug in terms of "how much better" the drug was than the "placebo
382:
level of "placebo response" than one would expect is an index of the degree to which, in some particular way, the
116:) that is not actually turned on. Also, due to the body's natural healing ability and statistical effects such as
1861:
125:
what treatments, delivered in what circumstances, to which patients, in what conditions, are the most effective.
2571:
2147:
645:, very largely diluted. This was given regularly, and became well known in my wards as the placeboic remedy for
2791:
2609:
2331:
1691:"Evaluating Mesmerism, Paris, 1784: the controversy over the blinded placebo controlled trials has not stopped"
339:. The results of these comparisons then determine whether or not a particular drug is considered efficacious.
2757:
2442:
969:
712:". The subjects were randomly divided into four test groups. He prepared four test drugs, involving various
720:. The structure of this trial is significant because, in those days, the only time placebos were ever used "
2736:
1738:
Booth C (August 2005). "The rod of
Aesculapios: John Haygarth (1740–1827) and Perkins' metallic tractors".
107:
Patients frequently show improvement even when given a sham or "fake" treatment. Such intentionally inert
2700:
2672:
2601:
2355:
1207:
1135:
1642:"Mesmer's 1780 proposal for a controlled trial to test his method of treatment using "animal magnetism""
1077:
the medical profession upon itself. Paragraph 29 of the
Declaration makes specific mention of placebos:
2786:
2750:
2426:
1029:
188:
136:
assessment of the efficacy of medicinal drugs or treatments. Such a test or clinical trial is called a
618:
wooden tractors with a set of allegedly "active" metal tractors, and published his findings in a book
93:" treatment which is specifically designed to have no real effect. Placebos are most commonly used in
2545:
1905:
Lasagna L, Mosteller F, von Felsinger JM, Beecher HK (June 1954). "A study of the placebo response".
1172:
1056:
220:
2188:
1301:
144:
type. A study whose control is a previously tested treatment, rather than no treatment, is called a
2796:
2483:
2431:
2311:
1177:
1157:
968:
It used to be thought that the first-ever randomized clinical trial was the trial conducted by the
598:, but examined the significantly different practices of his associate Charles d'Eslon (1739–1786).
265:
The outcomes within each group are observed, and compared with each other, allowing us to measure:
54:
2529:
2399:
2377:
2346:
2321:
2304:
2159:
1060:
662:
452:
113:
883:
On initial analysis, there was no difference between the self-reported "success rates" of Drugs
367:
level of "placebo response" than one would expect is an index of the degree to which the drug's
149:
141:
2680:
2517:
2438:
1296:
1197:
977:
677:) would have been prevented if that subject had been immediately given the "active treatment".
500:
257:): who receive no treatment of any kind (and whose condition, therefore, is allowed to run its
117:
2521:
2408:
2316:
2280:
2175:
945:
212:
133:
2245:
2487:
2046:
1049:
1001:
956:
195:
ensures that blinding is as effective as possible within ethical and practical constrains.
8:
2394:
2326:
1187:
631:
567:
421:
People who were already healthier were more able or more inclined to follow the protocol.
2647:
2597:
2412:
2341:
2299:
2014:
1989:
1966:
1941:
1763:
1715:
1690:
1666:
1641:
1613:
1588:
1563:
1541:
1411:
1392:
1260:
1243:
1217:
1182:
1167:
717:
480:
468:
456:
424:
Compliant people were more diligent and health-conscious in all aspects of their lives.
170:
129:
86:
1380:
2721:
2685:
2652:
2577:
2499:
2276:
2219:
2111:
2070:
2019:
1971:
1922:
1918:
1798:
1794:
1767:
1755:
1720:
1671:
1620:
1593:
1533:
1498:
1463:
1384:
1349:
1314:
1265:
1222:
1025:
343:
192:
180:
1545:
895:(84%, 80%, and 80% respectively) (the "success rate" of the simulating placebo Drug
2495:
2416:
2370:
2365:
2211:
2163:
2101:
2060:
2009:
2001:
1961:
1953:
1914:
1790:
1747:
1710:
1702:
1661:
1653:
1583:
1575:
1525:
1490:
1455:
1396:
1376:
1341:
1306:
1255:
1041:
1017:
611:
504:
460:
94:
1086:
In 2002, World Medical Association issued the following elaborative announcement:
2690:
2513:
2468:
2035:
1867:
658:
654:
418:
Adhering to the protocol had a psychological effect, i.e. genuine placebo effect.
356:
1459:
911:
separate group, there was a significant difference the "success rates" of Drugs
2716:
2637:
2589:
2382:
2294:
1751:
1657:
1434:
1192:
1021:
571:
551:
515:
445:
410:
184:
121:
101:
1957:
1529:
2780:
2695:
2662:
2657:
2148:
https://web.archive.org/web/20090220183350/http://www.wma.net/e/policy/b3.htm
1310:
1284:
1123:
1070:
the medical profession by the "Doctors' Trial" judges, whilst the second was
607:
539:
508:
2537:
2421:
2223:
2115:
2074:
2023:
2005:
1926:
1802:
1759:
1724:
1675:
1494:
1388:
1353:
1269:
1119:
1037:
985:
973:
940:
686:
670:
666:
595:
519:
2047:
Patulin Clinical Trials Committee, Medical Research Council (April 2004).
1975:
1597:
1537:
1502:
1467:
1318:
2731:
2585:
2458:
2448:
2167:
2106:
2089:
2065:
2048:
1706:
782:
713:
708:
Jellinek set up a complex trial involving 199 subjects, all of whom had "
2242:
A source of historical texts on fair tests of treatments in health care.
1579:
1090:
Note of clarification on paragraph 29 of the WMA Declaration of Helsinki
2533:
2525:
2491:
2453:
2360:
2215:
1889:
JSTORE "Clinical Tests on Comparative Effectiveness of Analgesic Drugs"
1345:
1131:
1127:
646:
464:
441:
434:
199:
620:
On the Imagination as a Cause & as a Cure of Disorders of the Body
592:
French Royal Commission investigated the existence of animal magnetism
132:
component of most clinical trials, which attempt to make some sort of
2593:
2581:
1781:
Green SA (December 2002). "The origins of modern clinical research".
1480:
1162:
1024:, which was issued in August 1947, as a consequence of the so-called
674:
559:
1904:
1888:
1445:
906:
However, further analysis on the trial demonstrated that ingredient
2627:
1045:
1040:, offers ten principles for legitimate medical research, including
989:
2632:
1202:
642:
543:
535:
108:
90:
625:
1564:"James Lind (1716-94) of Edinburgh and the treatment of scurvy"
1033:
563:
523:
1366:
2275:
575:
555:
531:
491:
246:): who receive a placebo drug that simulates the active drug.
2131:"Commentary on an early placebo controlled trial in Finland"
1568:
Archives of Disease in Childhood: Fetal and Neonatal Edition
444:. This kind of unblinding can be reduced with the use of an
1360:
680:
547:
176:
198:
During the course of an experiment, a participant becomes
74:
951:
It indicated that, whilst any given placebo was inert, a
610:
investigated the efficacy of medical instruments called "
1331:
1515:
1412:"Creative consulting: what modifies a healing response"
100:
The purpose of the placebo group is to account for the
899:
was 52%); and, from this, it appeared that ingredient
327:
It is a matter of interpretation whether the value of
2049:"Clinical trial of patulin in the common cold. 1944"
716:
of the three drug constituents, with a placebo as a
495:
A portrait of Scottish doctor James Lind (1716–1794)
219:" has emerged; and trials are conducted using three
1688:
78:
Prescription placebos used in research and practice
1990:"Streptomycin treatment of pulmonary tuberculosis"
1612:
1094:is available, under the following circumstances:
546:three times a day, a course of sea-water (half a
467:while the control group received a large dose of
2778:
2201:
1282:
995:those " by bed-rest alone" (the control group).
2160:"Journal of Clinical Psychology: Vol 61, No 7"
2087:
2261:
1619:. Cambridge, UK: Cambridge University Press.
980:. In this trial, there were two test groups:
626:Flint and placebo active treatment comparison
459:in which the experimental group received the
128:Therefore, the use of placebos is a standard
1815:
1639:
963:
1883:
1881:
1879:
1877:
1875:
1689:Best M, Neuhauser D, Slavin L (June 2003).
1610:
1483:Journal of the American Medical Association
2268:
2254:
2128:
1939:
1285:"Defining empirically supported therapies"
1011:
653:Flint treated 13 hospital inmates who had
2105:
2064:
2013:
1965:
1714:
1665:
1587:
1300:
1283:Chambless DL, Hollon SD (February 1998).
1259:
1241:
681:Jellinek and headache remedy ingredients
206:
2560:Preventable fraction among the unexposed
2556:Attributable fraction for the population
2133:. The James Lind Library. Archived from
1895:, Vol.2, No.5, (October 1946), pp.87–91.
1872:
1858:American Journal of the Medical Sciences
1852:
1850:
1848:
1846:
1780:
490:
486:
479:For broader coverage of this topic, see
398:
333:efficacy of the entire treatment process
73:
2564:Preventable fraction for the population
2552:Attributable fraction among the exposed
1737:
1557:
1555:
14:
2779:
1409:
1134:) are now required to have scientific
1113:
934:Two conclusions came from this trial:
542:) three times a day, two spoonfuls of
390:the active drug in an appropriate way.
2249:
1843:
1143:, devoted an issue to the issue of "
948:origins of the condition in question.
781:: a 'simulator', contained "ordinary
534:per day, twenty-five drops of elixir
518:when he investigated the efficacy of
359:, it is reasonable to conclude that:
148:study, because its control is of the
2727:Correlation does not imply causation
2643:Animal testing on non-human primates
1561:
1552:
1213:Royal Commission on Animal Magnetism
1145:The Placebo Concept in Psychotherapy
235:): who receive the active test drug.
211:The practice of using an additional
55:move details into the article's body
26:
2088:Chalmers I, Clarke M (April 2004).
972:(MRC) in 1948 into the efficacy of
601:
585:
337:magnitude of the "placebo response"
24:
1562:Dunn, Peter M. (January 1, 1997).
530:, the remedies were: one quart of
451:An active placebo was used in the
288:The efficacy of the active drug's
269:The efficacy of the active drug's
25:
2808:
2233:
1860:, Vol.46, (July 1863), pp.17–36.
1052:towards experiment participants.
614:", by comparing the results from
357:with all other things being equal
140:study, and its control is of the
1825:. Bath: Crutwell. Archived from
1795:10.1097/00003086-200212000-00039
705:was in particular short supply.
31:
2195:
2152:
2141:
2122:
2081:
2040:
1982:
1933:
1898:
1809:
1774:
1731:
1682:
1633:
1604:
927:, he concluded that ingredient
378:the degree to which there is a
363:the degree to which there is a
2610:Pre- and post-test probability
2332:Patient and public involvement
2204:Journal of Clinical Psychology
2000:(4582): 769–82. October 1948.
1640:Donaldson IM (December 2005).
1509:
1474:
1439:
1427:
1403:
1325:
1276:
1235:
1141:Journal of Clinical Psychology
159:
13:
1:
1381:10.1016/S0140-6736(00)04169-6
1229:
1118:"Talking therapies" (such as
428:
2737:Sex as a biological variable
1919:10.1016/0002-9343(54)90441-6
903:was completely unnecessary.
403:
7:
2701:Intention-to-treat analysis
2673:Analysis of clinical trials
2602:Specificity and sensitivity
2356:Randomized controlled trial
1940:Yoshioka A (October 1998).
1460:10.1056/NEJM198010303031804
1208:Randomized controlled trial
1150:
349:
164:
10:
2813:
1752:10.1177/096777200501300310
1658:10.1177/014107680509801226
478:
474:
432:
215:as the trial's so-called "
168:
83:Placebo-controlled studies
18:Placebo-controlled studies
2745:
2710:Interpretation of results
2709:
2671:
2620:
2570:
2544:
2506:
2476:
2467:
2443:Nested case–control study
2393:
2340:
2287:
1958:10.1136/bmj.317.7167.1220
1530:10.2466/pr0.1966.19.1.211
1178:Clinical trial management
1173:Clinical data acquisition
1057:World Medical Association
964:MRC and randomized trials
311:: the difference between
292:: the difference between
273:: the difference between
2312:Academic clinical trials
1783:Clin. Orthop. Relat. Res
1311:10.1037/0022-006X.66.1.7
1242:Gaddum JH (March 1954).
1158:Academic clinical trials
970:Medical Research Council
562:, (a mixture containing
2530:Relative risk reduction
2378:Adaptive clinical trial
2322:Evidence-based medicine
2305:Adaptive clinical trial
1244:"Clinical pharmacology"
1061:Declaration of Helsinki
1012:Declaration of Helsinki
453:Marsh Chapel Experiment
89:group receives a sham "
2518:Number needed to treat
2183:Cite journal requires
2006:10.1136/bmj.2.4582.769
1615:A history of hypnotism
1495:10.1001/jama.270.6.742
1410:Reilly, David (2002).
1289:J Consult Clin Psychol
1198:Philosophy of medicine
1107:
1084:
978:pulmonary tuberculosis
651:
514:, conducted the first
496:
207:Natural history groups
118:regression to the mean
79:
2792:Design of experiments
2522:Number needed to harm
2409:Cross-sectional study
2361:Scientific experiment
2317:Clinical study design
1816:Haygarth, J. (1801).
1088:
1079:
1030:human experimentation
1016:From the time of the
639:
494:
487:James Lind and scurvy
399:Implementation issues
307:The magnitude of the
213:natural history group
77:
2488:Cumulative incidence
1707:10.1136/qhc.12.3.232
1695:Qual Saf Health Care
1611:Gauld, Alan (1992).
976:in the treatment of
2395:Observational study
2327:Real world evidence
2281:experimental design
2129:Hemminki E (2005).
1893:Biometrics Bulletin
1580:10.1136/fn.76.1.F64
1188:Experimental design
1114:Non-drug treatments
1028:which examined the
365:considerably higher
2681:Risk–benefit ratio
2648:First-in-man study
2598:Case fatality rate
2439:Case–control study
2413:Longitudinal study
2240:James Lind Library
2216:10.1002/jclp.20133
2168:10.1002/jclp.v61:7
2107:10.1093/ije/dyh162
2066:10.1093/ije/dyh028
2034:2008-10-25 at the
1866:2009-03-01 at the
1346:10.1002/jclp.20128
1218:Scientific control
1183:Confounding factor
1168:Blinded experiment
984:those "treated by
718:scientific control
710:frequent headaches
497:
481:Placebo in history
380:considerably lower
171:Blinded experiment
138:placebo-controlled
114:ultrasound machine
80:
2787:Clinical research
2774:
2773:
2722:Survivorship bias
2686:Systematic review
2653:Multicenter trial
2616:
2615:
2606:Likelihood-ratios
2578:Clinical endpoint
2546:Population impact
2500:Period prevalence
2277:Clinical research
1626:978-0-521-48329-2
1375:(9258): 757–762.
1248:Proc. R. Soc. Med
1223:Scientific method
503:(1716–1794), the
369:active ingredient
344:crossover studies
290:active ingredient
221:randomly selected
193:clinical protocol
181:confirmation bias
72:
71:
51:length guidelines
16:(Redirected from
2804:
2621:Trial/test types
2496:Point prevalence
2474:
2473:
2417:Ecological study
2400:EBM II-2 to II-3
2371:Open-label trial
2366:Blind experiment
2342:Controlled study
2270:
2263:
2256:
2247:
2246:
2228:
2227:
2199:
2193:
2192:
2186:
2181:
2179:
2171:
2156:
2150:
2145:
2139:
2138:
2126:
2120:
2119:
2109:
2085:
2079:
2078:
2068:
2044:
2038:
2027:
2017:
1986:
1980:
1979:
1969:
1952:(7167): 1220–3.
1937:
1931:
1930:
1902:
1896:
1887:Jellinek, E. M.
1885:
1870:
1854:
1841:
1840:
1838:
1837:
1831:
1824:
1813:
1807:
1806:
1778:
1772:
1771:
1735:
1729:
1728:
1718:
1686:
1680:
1679:
1669:
1637:
1631:
1630:
1618:
1608:
1602:
1601:
1591:
1559:
1550:
1549:
1513:
1507:
1506:
1478:
1472:
1471:
1443:
1437:
1431:
1425:
1423:
1407:
1401:
1400:
1364:
1358:
1357:
1329:
1323:
1322:
1304:
1280:
1274:
1273:
1263:
1239:
1042:informed consent
1018:Hippocratic Oath
612:Perkins tractors
602:Perkins tractors
586:Animal magnetism
550:every day), two
309:placebo response
146:positive-control
67:
64:
58:
49:Please read the
35:
34:
27:
21:
2812:
2811:
2807:
2806:
2805:
2803:
2802:
2801:
2797:Clinical trials
2777:
2776:
2775:
2770:
2741:
2705:
2667:
2612:
2566:
2540:
2514:Risk difference
2502:
2463:
2397:
2389:
2344:
2336:
2300:Trial protocols
2283:
2274:
2236:
2231:
2200:
2196:
2184:
2182:
2173:
2172:
2158:
2157:
2153:
2146:
2142:
2127:
2123:
2094:Int J Epidemiol
2086:
2082:
2053:Int J Epidemiol
2045:
2041:
2036:Wayback Machine
1988:
1987:
1983:
1938:
1934:
1903:
1899:
1886:
1873:
1868:Wayback Machine
1855:
1844:
1835:
1833:
1829:
1822:
1814:
1810:
1779:
1775:
1736:
1732:
1687:
1683:
1638:
1634:
1627:
1609:
1605:
1560:
1553:
1514:
1510:
1479:
1475:
1454:(18): 1038–41.
1448:N. Engl. J. Med
1444:
1440:
1432:
1428:
1408:
1404:
1365:
1361:
1330:
1326:
1302:10.1.1.586.4638
1281:
1277:
1240:
1236:
1232:
1227:
1153:
1130:, and non-drug
1116:
1092:
1091:
1036:doctors during
1014:
966:
941:hypochondriasis
931:was essential.
701:, and chemical
683:
655:rheumatic fever
628:
604:
588:
489:
484:
477:
437:
431:
406:
401:
373:not efficacious
352:
251:Natural history
209:
189:observer effect
173:
167:
162:
68:
62:
59:
48:
45:may be too long
40:This article's
36:
32:
23:
22:
15:
12:
11:
5:
2810:
2800:
2799:
2794:
2789:
2772:
2771:
2769:
2768:
2765:List of topics
2761:
2754:
2746:
2743:
2742:
2740:
2739:
2734:
2729:
2724:
2719:
2717:Selection bias
2713:
2711:
2707:
2706:
2704:
2703:
2698:
2693:
2688:
2683:
2677:
2675:
2669:
2668:
2666:
2665:
2660:
2655:
2650:
2645:
2640:
2638:Animal testing
2635:
2630:
2624:
2622:
2618:
2617:
2614:
2613:
2590:Mortality rate
2576:
2574:
2568:
2567:
2550:
2548:
2542:
2541:
2512:
2510:
2504:
2503:
2482:
2480:
2471:
2465:
2464:
2462:
2461:
2456:
2451:
2446:
2436:
2435:
2434:
2429:
2419:
2405:
2403:
2391:
2390:
2388:
2387:
2386:
2385:
2383:Platform trial
2375:
2374:
2373:
2368:
2363:
2352:
2350:
2338:
2337:
2335:
2334:
2329:
2324:
2319:
2314:
2309:
2308:
2307:
2302:
2295:Clinical trial
2291:
2289:
2285:
2284:
2273:
2272:
2265:
2258:
2250:
2244:
2243:
2235:
2234:External links
2232:
2230:
2229:
2210:(7): 893–908.
2194:
2185:|journal=
2151:
2140:
2137:on 2008-08-28.
2121:
2080:
2039:
1981:
1932:
1897:
1871:
1842:
1808:
1789:(405): 311–9.
1773:
1730:
1681:
1632:
1625:
1603:
1551:
1508:
1473:
1438:
1426:
1402:
1359:
1334:J Clin Psychol
1324:
1275:
1254:(3): 195–204.
1233:
1231:
1228:
1226:
1225:
1220:
1215:
1210:
1205:
1200:
1195:
1193:Medical ethics
1190:
1185:
1180:
1175:
1170:
1165:
1160:
1154:
1152:
1149:
1115:
1112:
1103:
1102:
1099:
1026:Doctors' Trial
1022:Nuremberg Code
1013:
1010:
997:
996:
993:
965:
962:
961:
960:
949:
878:
877:
859:
842:
825:
787:
786:
775:
760:
745:
682:
679:
627:
624:
603:
600:
587:
584:
572:balsam of Peru
558:each day, and
516:clinical trial
488:
485:
476:
473:
446:active placebo
433:Main article:
430:
427:
426:
425:
422:
419:
411:mortality rate
405:
402:
400:
397:
392:
391:
388:not simulating
376:
351:
348:
331:indicates the
325:
324:
305:
286:
263:
262:
247:
236:
208:
205:
185:placebo effect
169:Main article:
166:
163:
161:
158:
122:clinical trial
102:placebo effect
70:
69:
39:
37:
30:
9:
6:
4:
3:
2:
2809:
2798:
2795:
2793:
2790:
2788:
2785:
2784:
2782:
2767:
2766:
2762:
2760:
2759:
2755:
2753:
2752:
2748:
2747:
2744:
2738:
2735:
2733:
2730:
2728:
2725:
2723:
2720:
2718:
2715:
2714:
2712:
2708:
2702:
2699:
2697:
2696:Meta-analysis
2694:
2692:
2689:
2687:
2684:
2682:
2679:
2678:
2676:
2674:
2670:
2664:
2663:Vaccine trial
2661:
2659:
2658:Seeding trial
2656:
2654:
2651:
2649:
2646:
2644:
2641:
2639:
2636:
2634:
2631:
2629:
2626:
2625:
2623:
2619:
2611:
2607:
2603:
2599:
2595:
2591:
2587:
2583:
2579:
2575:
2573:
2569:
2565:
2561:
2557:
2553:
2549:
2547:
2543:
2539:
2535:
2531:
2527:
2523:
2519:
2515:
2511:
2509:
2505:
2501:
2497:
2493:
2489:
2485:
2481:
2479:
2475:
2472:
2470:
2466:
2460:
2457:
2455:
2452:
2450:
2447:
2444:
2440:
2437:
2433:
2430:
2428:
2427:Retrospective
2425:
2424:
2423:
2420:
2418:
2414:
2410:
2407:
2406:
2404:
2401:
2396:
2392:
2384:
2381:
2380:
2379:
2376:
2372:
2369:
2367:
2364:
2362:
2359:
2358:
2357:
2354:
2353:
2351:
2348:
2347:EBM I to II-1
2343:
2339:
2333:
2330:
2328:
2325:
2323:
2320:
2318:
2315:
2313:
2310:
2306:
2303:
2301:
2298:
2297:
2296:
2293:
2292:
2290:
2286:
2282:
2278:
2271:
2266:
2264:
2259:
2257:
2252:
2251:
2248:
2241:
2238:
2237:
2225:
2221:
2217:
2213:
2209:
2205:
2198:
2190:
2177:
2169:
2165:
2161:
2155:
2149:
2144:
2136:
2132:
2125:
2117:
2113:
2108:
2103:
2100:(2): 253–60.
2099:
2095:
2091:
2084:
2076:
2072:
2067:
2062:
2058:
2054:
2050:
2043:
2037:
2033:
2030:
2025:
2021:
2016:
2011:
2007:
2003:
1999:
1995:
1991:
1985:
1977:
1973:
1968:
1963:
1959:
1955:
1951:
1947:
1943:
1936:
1928:
1924:
1920:
1916:
1912:
1908:
1901:
1894:
1890:
1884:
1882:
1880:
1878:
1876:
1869:
1865:
1862:
1859:
1853:
1851:
1849:
1847:
1832:on 2008-05-16
1828:
1821:
1820:
1812:
1804:
1800:
1796:
1792:
1788:
1784:
1777:
1769:
1765:
1761:
1757:
1753:
1749:
1746:(3): 155–61.
1745:
1741:
1734:
1726:
1722:
1717:
1712:
1708:
1704:
1700:
1696:
1692:
1685:
1677:
1673:
1668:
1663:
1659:
1655:
1652:(12): 572–5.
1651:
1647:
1643:
1636:
1628:
1622:
1617:
1616:
1607:
1599:
1595:
1590:
1585:
1581:
1577:
1573:
1569:
1565:
1558:
1556:
1547:
1543:
1539:
1535:
1531:
1527:
1524:(1): 211–27.
1523:
1519:
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1504:
1500:
1496:
1492:
1488:
1484:
1477:
1469:
1465:
1461:
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1430:
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1390:
1386:
1382:
1378:
1374:
1370:
1363:
1355:
1351:
1347:
1343:
1340:(7): 819–34.
1339:
1335:
1328:
1320:
1316:
1312:
1308:
1303:
1298:
1294:
1290:
1286:
1279:
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1267:
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1257:
1253:
1249:
1245:
1238:
1234:
1224:
1221:
1219:
1216:
1214:
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1161:
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1142:
1137:
1133:
1129:
1125:
1124:psychotherapy
1121:
1111:
1106:
1100:
1097:
1096:
1095:
1087:
1083:
1078:
1076:
1073:
1069:
1066:
1062:
1058:
1055:In 1964, the
1053:
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1047:
1044:, absence of
1043:
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1031:
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1019:
1009:
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715:
711:
706:
704:
700:
696:
692:
688:
678:
676:
672:
668:
664:
663:complications
660:
656:
650:
648:
644:
638:
635:
633:
623:
621:
617:
613:
609:
608:John Haygarth
599:
597:
593:
590:In 1784, the
583:
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569:
565:
561:
557:
553:
549:
545:
541:
540:sulfuric acid
537:
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521:
517:
513:
512:
506:
505:ship's doctor
502:
493:
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470:
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454:
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272:
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63:December 2020
56:
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2538:Hazard ratio
2422:Cohort study
2207:
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2197:
2176:cite journal
2154:
2143:
2135:the original
2124:
2097:
2093:
2083:
2059:(2): 243–6.
2056:
2052:
2042:
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1993:
1984:
1949:
1945:
1935:
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1910:
1906:
1900:
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1834:. Retrieved
1827:the original
1818:
1811:
1786:
1782:
1776:
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1698:
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1571:
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1486:
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1120:hypnotherapy
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1080:
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1054:
1038:World War II
1015:
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986:streptomycin
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748:
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729:
721:
714:permutations
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694:
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687:World War II
684:
671:endocarditis
667:pericarditis
652:
640:
636:
632:Austin Flint
629:
619:
615:
605:
596:Franz Mesmer
589:
580:
527:
522:in cases of
520:citrus fruit
510:
498:
450:
438:
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393:
387:
383:
379:
372:
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364:
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250:
243:
240:Placebo drug
239:
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228:
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155:
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137:
134:quantitative
127:
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43:lead section
41:
2732:Null result
2691:Replication
2586:Infectivity
2508:Association
2459:Case report
2449:Case series
2432:Prospective
1740:J Med Biogr
1646:J R Soc Med
1518:Psychol Rep
1416:Student BMJ
1295:(1): 7–18.
1059:issued the
1050:beneficence
946:psychogenic
657:; 11 were "
461:psychedelic
229:Active drug
160:Methodology
2781:Categories
2534:Odds ratio
2526:Risk ratio
2492:Prevalence
2478:Occurrence
2454:Case study
1907:Am. J. Med
1836:2009-01-09
1369:The Lancet
1230:References
1136:validation
1132:psychiatry
1128:counseling
647:rheumatism
501:James Lind
465:psilocybin
463:substance
442:unblinding
435:Unblinding
429:Unblinding
203:reported.
2594:Morbidity
2582:Virulence
2484:Incidence
1768:208293370
1297:CiteSeerX
1163:Bioethics
1065:suggested
953:responder
675:pneumonia
606:In 1799,
560:electuary
511:Salisbury
499:In 1747,
404:Adherence
271:treatment
217:third arm
200:unblinded
53:and help
2758:Glossary
2751:Category
2628:In vitro
2469:Measures
2288:Overview
2224:15827997
2116:15082623
2075:15082620
2032:Archived
2029:see also
2024:18890300
1994:Br Med J
1927:13158365
1864:Archived
1803:12461388
1760:16059528
1725:12792017
1676:16319443
1546:16508547
1435:27100270
1389:11253970
1354:15827994
1270:13155508
1151:See also
1046:coercion
990:bed-rest
630:In 1863
554:and one
350:Indexing
261:course).
179:such as
165:Blinding
150:positive
142:negative
2633:In vivo
2015:2091872
1976:9794865
1967:1114162
1716:1743715
1667:1299353
1598:9059193
1589:1720613
1538:5942087
1503:8336377
1468:6999345
1422:: 1–44.
1397:6740675
1319:9489259
1261:1918604
1203:Placebo
1082:exists.
1072:imposed
783:lactate
643:quassia
568:mustard
552:oranges
544:vinegar
536:vitriol
475:History
384:placebo
335:or the
319:(i.e.,
300:(i.e.,
281:(i.e.,
259:natural
253:group (
242:group (
231:group (
130:control
109:placebo
95:blinded
91:placebo
87:control
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1002:biased
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957:screen
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891:, and
740:, and
697:, and
673:, and
574:, and
564:garlic
524:scurvy
469:niacin
187:, the
183:, the
177:biases
2572:Other
1830:(PDF)
1823:(PDF)
1764:S2CID
1542:S2CID
1393:S2CID
802:, or
777:Drug
762:Drug
747:Drug
728:Drug
659:acute
616:dummy
576:myrrh
556:lemon
532:cider
2411:vs.
2279:and
2220:PMID
2189:help
2112:PMID
2071:PMID
2020:PMID
1972:PMID
1923:PMID
1799:PMID
1756:PMID
1721:PMID
1672:PMID
1621:ISBN
1594:PMID
1534:PMID
1499:PMID
1464:PMID
1424:p.28
1385:PMID
1350:PMID
1315:PMID
1266:PMID
1034:Nazi
988:and
770:and
755:and
548:pint
509:HMS
455:, a
329:P-NH
321:P-NH
315:and
296:and
283:A-NH
277:and
249:The
238:The
227:The
2212:doi
2164:doi
2102:doi
2061:doi
2010:PMC
2002:doi
1962:PMC
1954:doi
1950:317
1946:BMJ
1915:doi
1791:doi
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1748:doi
1711:PMC
1703:doi
1662:PMC
1654:doi
1584:PMC
1576:doi
1526:doi
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1456:doi
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