Randomized controlled trial
Provided it is designed well, conducted properly, and enrolls enough participants, an RCT may achieve sufficient control over these confounding factors to deliver a useful comparison of the treatments studied.This blinding principle is ideally also extended as much as possible to other parties including researchers, technicians, data analysts, and evaluators.Blinded RCTs are commonly used to test the efficacy of medical interventions and may additionally provide information about adverse effects, such as drug reactions.This suggestion contrasted starkly with the prevalent Enlightenment-era attitude that scientific observation can only be objectively valid when undertaken by a well-educated, informed scientist.[15][16][17] The earliest experiments comparing treatment and control groups were published by Robert Woodworth and Edward Thorndike in 1901,[18] and by John E. Coover and Frank Angell in 1907.[22] The first published Randomized Controlled Trial in medicine appeared in the 1948 paper entitled "Streptomycin treatment of pulmonary tuberculosis", which described a Medical Research Council investigation.[38][39] Medical journals have been slow in adapting policies requiring mandatory clinical trial registration as a prerequisite for publication.From most to least common in the healthcare literature, the major categories of RCT study designs are:[41] An analysis of the 616 RCTs indexed in PubMed during December 2006 found that 78% were parallel-group trials, 16% were crossover, 2% were split-body, 2% were cluster, and 2% were factorial.The failure to reject the null hypothesis would imply that the treatment shows no statistically significant effect on the treated in a given test.[62] An RCT may be blinded, (also called "masked") by "procedures that prevent study participants, caregivers, or outcome assessors from knowing which intervention was received.[67] In 2008 a study concluded that the results of unblinded RCTs tended to be biased toward beneficial effects only if the RCTs' outcomes were subjective as opposed to objective;[61] for example, in an RCT of treatments for multiple sclerosis, unblinded neurologists (but not the blinded neurologists) felt that the treatments were beneficial.[68] In pragmatic RCTs, although the participants and providers are often unblinded, it is "still desirable and often possible to blind the assessor or obtain an objective source of data for evaluation of outcomes."[73] The CONSORT 2010 checklist contains 25 items (many with sub-items) focusing on "individually randomised, two group, parallel trials" which are the most common type of RCT.[78][79] The authors of the 2000 findings questioned the belief that "observational studies should not be used for defining evidence-based medical care" and that RCTs' results are "evidence of the highest grade.[80] According to a 2014 (updated in 2024) Cochrane review, there is little evidence for significant effect differences between observational studies and randomized controlled trials.The key context that limited the general applicability of this conclusion was that the aircraft were parked on the ground, and participants had only jumped about two feet.[83][102] Interventions to prevent events that occur only infrequently (e.g., sudden infant death syndrome) and uncommon adverse outcomes (e.g., a rare side effect of a drug) would require RCTs with extremely large sample sizes and may, therefore, best be assessed by observational studies.[83] Due to the costs of running RCTs, these usually only inspect one variable or very few variables, rarely reflecting the full picture of a complicated medical situation; whereas the case report, for example, can detail many aspects of the patient's medical situation (e.g. patient history, physical examination, diagnosis, psychosocial aspects, follow up).[citation needed] Historical control trials (HCT) exploit the data of previous RCTs to reduce the sample size; however, these approaches are controversial in the scientific community and must be handled with care.Some writers from a medical or health background have argued that existing research in a range of social science disciplines lacks rigour, and should be improved by greater use of randomized control trials.[111] Researchers in transport science argue that public spending on programmes such as school travel plans could not be justified unless their efficacy is demonstrated by randomized controlled trials.They concluded that most of the studies were of low quality and advocated the use of randomized controlled trials wherever possible in future transport research.Dr. Steve Melia[114] took issue with these conclusions, arguing that claims about the advantages of RCTs, in establishing causality and avoiding bias, have been exaggerated.
scientific experimentclinical trialsmedical devicesdiagnostic proceduresrandomly allocatingconfounding factorsclinical researchplaceboblindedselection biasexperimenter and subject biasesgold standardinterventionsdrug reactionsinitialismscientific literatureclinical trialJames LindscurvyFrench Royal Commission on Animal MagnetismmesmerismClaude BernardEnlightenmentW. H. R. RiversRandomized experimentspsychologyCharles Sanders PeirceJoseph Jastroweducationtreatment and control groupsRobert WoodworthEdward ThorndikeJohn E. CooverFrank AngellJerzy NeymanRonald A. FisherStreptomycintuberculosisMedical Research CouncilAustin Bradford Hillheart attackCochrane LibraryConsolidated Standards of Reporting Trialsclinical equipoiseethicsZelen's designscreeninginformed consenttherapeutic misconceptionstudy designParallel-groupCrossoverClusterFactorialPubMedPragmatic clinical trialstatistically significantrandomizationconfoundingstatistical powersubgroup analysescovariatesbiasedrobust"restricted" randomizationPermuted-block randomizationstratified randomizationmulticenter trialminimizationAllocation concealmentconfoundersprotocolmeta-analysessubjectiveobjectiveSample size determinationstatistical testnull hypothesisBlinded experimentphysical therapyCONSORT Statementopen-labelmultiple sclerosisdichotomouslogistic regressionpeginterferon alfa-2ahepatitis Canalysis of covarianceatorvastatinacute coronary syndromecensoredsurvival analysisKaplan–Meier estimatorsCox proportional hazards modelscoronary heart diseasehormone replacement therapy in menopauseintention-to-treat analysisimputedsubgroup analysismultiple comparisonsCONSORT 2010 StatementCONSORT extensionsThe New England Journal of Medicineobservational studiesJournal of the American Medical Associationcisplatinmetastatictesticular cancertype I ("false positive") and type II ("false negative") statistical errorssample sizesPeer reviewscientific methodsystematic biasscientific evidencehierarchy of evidencesystematic reviewsevidence-based practiceNational Health and Medical Research Councilsystematic reviewclinical practice guidelineUnited States Preventive Services Task Forceinternal validityOxford Centre for Evidence-based MedicineConfidence IntervalFood and Drug Administrationantiarrhythmic agents