Editing Randomized controlled trial (section)

=== Allocation concealment ===
{{main|Allocation concealment}}
"Allocation concealment" (defined as "the procedure for protecting the randomization process so that the treatment to be allocated is not known before the patient is entered into the study") is important in RCTs.<ref name="Forder-2005">{{Cite journal |vauthors=Forder PM, Gebski VJ, Keech AC |date=January 2005 |title=Allocation concealment and blinding: when ignorance is bliss |journal=The Medical Journal of Australia |volume=182 |issue=2 |pages=87–89 |doi=10.5694/j.1326-5377.2005.tb06584.x |pmid=15651970 |s2cid=202149}}</ref> In practice, clinical investigators in RCTs often find it difficult to maintain impartiality. Stories abound of investigators holding up sealed envelopes to lights or ransacking offices to determine group assignments in order to dictate the assignment of their next patient.<ref name="Schulz-2002">{{Cite journal |vauthors=Schulz KF, Grimes DA |date=February 2002 |title=Allocation concealment in randomised trials: defending against deciphering |url=https://www.who.int/entity/rhl/LANCET_614-618.pdf |journal=Lancet |volume=359 |issue=9306 |pages=614–618 |doi=10.1016/S0140-6736(02)07750-4 |pmid=11867132 |s2cid=12902486 |archive-url=https://wayback.archive-it.org/all/20120911210240/http://www.who.int/entity/rhl/LANCET_614-618.pdf |archive-date=September 11, 2012}}</ref> Such practices introduce selection bias and [[Lurking variable|confounders]] (both of which should be minimized by randomization), possibly distorting the results of the study.<ref name="Schulz-2002" /> Adequate allocation concealment should defeat patients and investigators from discovering treatment allocation once a study is underway and after the study has concluded.  Treatment related side-effects or adverse events may be specific enough to reveal allocation to investigators or patients thereby introducing bias or influencing any subjective parameters collected by investigators or requested from subjects.{{cn|date=November 2023}}

Some standard methods of ensuring allocation concealment include sequentially numbered, opaque, sealed envelopes (SNOSE); sequentially numbered containers; pharmacy controlled randomization; and central randomization.<ref name="Schulz-2002" /> It is recommended that allocation concealment methods be included in an RCT's [[Clinical trial protocol|protocol]], and that the allocation concealment methods should be reported in detail in a publication of an RCT's results; however, a 2005 study determined that most RCTs have unclear allocation concealment in their protocols, in their publications, or both.<ref name="Pildal-2005">{{Cite journal |vauthors=Pildal J, Chan AW, Hróbjartsson A, Forfang E, Altman DG, Gøtzsche PC |date=May 2005 |title=Comparison of descriptions of allocation concealment in trial protocols and the published reports: cohort study |journal=BMJ |volume=330 |issue=7499 |page=1049 |doi=10.1136/bmj.38414.422650.8F |pmc=557221 |pmid=15817527}}</ref> On the other hand, a 2008 study of 146 [[meta-analysis|meta-analyses]] concluded that the results of RCTs with inadequate or unclear allocation concealment tended to be biased toward beneficial effects only if the RCTs' outcomes were [[Subjectivity|subjective]] as opposed to [[Objectivity (philosophy)|objective]].<ref name="Wood-2008">{{Cite journal |vauthors=Wood L, Egger M, Gluud LL, Schulz KF, Jüni P, Altman DG, Gluud C, Martin RM, Wood AJ, Sterne JA |date=March 2008 |title=Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study |journal=BMJ |volume=336 |issue=7644 |pages=601–605 |doi=10.1136/bmj.39465.451748.AD |pmc=2267990 |pmid=18316340}}</ref>