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| title | chunk | source | category | tags | date_saved | instance |
|---|---|---|---|---|---|---|
| Randomized controlled trial | 2/7 | https://en.wikipedia.org/wiki/Randomized_controlled_trial | reference | science, encyclopedia | 2026-05-05T04:26:23.353341+00:00 | kb-cron |
== Ethics == Although subjects almost always provide informed consent for their participation in an RCT, studies since 1982 have documented that RCT subjects may believe that they are certain to receive treatment that is best for them personally; that is, they do not understand the difference between research and treatment. Determining the amount of information required to ensure informed consent can be difficult, and further research is necessary to determine the prevalence of and ways to address therapeutic misconception. Placebo-controlled trials have been deemed unethical in instances where not receiving treatment may lead to harm for the patient, such as an aggravation of symptoms or risk of death. Crossover trials, active-controlled trials, and other approaches have been used to mitigate this issue, though these options may not always be suitable for study, and have received their own criticism. Active-controlled trials in particular may raise ethical considerations regarding clinical equipoise. Although the principle of equipoise ("genuine uncertainty within the expert medical community... about the preferred treatment") is common to clinical trials and has been applied to RCTs, equipoise may be difficult to ascertain, and the ethics of RCTs have special considerations. It has been argued that equipoise itself is insufficient to justify RCTs. "Collective equipoise" may also conflict with a lack of personal equipoise (i.e., a personal belief that an intervention is effective), including that of the patient. Zelen's design, which has been used for some RCTs, randomizes subjects before they provide informed consent, which may be ethical for RCTs of screening and selected therapies, but is likely unethical "for most therapeutic trials." While some randomisation approaches have been used to minimize the risk that patients are exposed to less effective treatment, such as randomising patients with unequal rates, or adapting the rates during the trial's duration based on outcomes, these solutions have been criticized for raising more ethical problems than they resolve. Whilst the above issues have resulted in robust practice guidelines around the conduct of RCTs, formulating balanced regulations tends to be difficult. Strict protections may act in favor of indigenous populations, but could fail on a globalised setting, as their imposition urges the outsourcing of trials to countries with poorer standards and more economically vulnerable populations. Frameworks which place great emphasis on patient well-being have also been criticized by some as paternalistic. The RCT method variations may also create cultural effects that have not been well understood. For example, patients with terminal illness may join trials in the hope of being cured, even when treatments are unlikely to be successful.
=== Medical trial registration === In 2004, the International Committee of Medical Journal Editors (ICMJE) announced that all trials starting enrolment after July 1, 2005, must be registered prior to consideration for publication in one of the 12 member journals of the committee. However, trial registration may still occur late or not at all. Medical journals have been slow in adapting policies requiring mandatory clinical trial registration as a prerequisite for publication.
== Classifications ==
=== By study design === One way to classify RCTs is by study design. From most to least common in the healthcare literature, the major categories of RCT study designs are:
Parallel-group – each participant is randomly assigned to a group, and all the participants in the group receive (or do not receive) an intervention. Crossover – over time, each participant receives (or does not receive) an intervention in a random sequence. Stepped-wedge trial - " involves random and sequential crossover of clusters (of subjects) from control to intervention until all clusters are exposed." In the past, this design has been called a "waiting list designs" or "phased implementations." Cluster – pre-existing groups of participants (e.g., villages, schools) are randomly selected to receive (or not receive) an intervention. Factorial – each participant is randomly assigned to a group that receives a particular combination of interventions or non-interventions (e.g., group 1 receives vitamin X and vitamin Y, group 2 receives vitamin X and placebo Y, group 3 receives placebo X and vitamin Y, and group 4 receives placebo X and placebo Y). 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.
=== By outcome of interest (efficacy vs. effectiveness) ===
RCTs can be classified as "explanatory" or "pragmatic." Explanatory RCTs test efficacy in a research setting with highly selected participants and under highly controlled conditions. In contrast, pragmatic RCTs (pRCTs) test effectiveness in everyday practice with relatively unselected participants and under flexible conditions; in this way, pragmatic RCTs can "inform decisions about practice."
=== By hypothesis (superiority vs. noninferiority vs. equivalence) ===
Another classification of RCTs categorizes them as "superiority trials", "noninferiority trials", and "equivalence trials", which differ in methodology and reporting. Most RCTs are superiority trials, in which one intervention is hypothesized to be superior to another in a statistically significant way. Some RCTs are noninferiority trials "to determine whether a new treatment is no worse than a reference treatment." Other RCTs are equivalence trials in which the hypothesis is that two interventions are indistinguishable from each other.
== Randomization == The advantages of proper randomization in RCTs include: