Allocation+concealment

What is allocation concealment?
toc Allocation concealment keeps the person enrolling participants in a trial from knowing the randomization sequence prior to group assignment, preventing selection bias ("systematic differences between baseline characteristics of the groups being compared" Higgins]). If the allocation sequence is not adequately concealed, the person assigning study participants to their groups may use prognostic factors to decide who should go into which group. For example, if a physician believes that their patient will benefit from being assigned to the intervention group, they might delay enrollment until they can get that patient into the desired group. This can result in a group of participants with a common prognostic factor being assigned preferentially to one group over another, making the groups systematically different. In this way, it will be unclear whether any observed treatment effect is due to the intervention, or related instead to that prognostic factor.

//How does allocation concealment differ from blinding?// Allocation concealment prevents study personnel and participants from knowing the allocation sequence //**prior to**// group assignment. This is separate from blinding, which keeps group assignment hidden //**after**// group assignment. Unlike blinding, allocation concealment can **//always//** be done.

Tools

 * Appropriate means of concealing group allocation:**
 * Central allocation (including telephone, web-based, and pharmacy-controlled randomization)
 * Sequentially numbered drug containers of identical appearance
 * Sequentially numbered, opaque, sealed envelopes

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Case study

 * Allocation concealment in pop culture**

//Synopsis:// (Season 7, Episode 19 - It's A Long Way Back) Dr. Meredith Grey and Dr. Derek Shepherd are conducting a clinical trial evaluating the effectiveness of a new treatment (versus placebo) for Alzheimer's disease. The Chief's wife, Adele Webber, has been diagnosed with Alzheimer's and has been enrolled in the trial. When Meredith suggests giving Adele the treatment outside of the study protocol to avoid the chance that she will be assigned to receive the placebo, Derek tells her that it would ruin the trial. Within the study protocol, the allocation sequence has been generated and stored in manilla envelopes in the pharmacy. When Adele is scheduled for her surgery, Meredith sneaks into the pharmacy, opens the envelope meant for Adele, and switches the assignment when she learns that Adele would be assigned to the placebo group.

//Why Meredith shouldn't have peeked:// By intentionally changing the group assignment, Meredith introduced selection bias into the trial. She is assuming that the new treatment will be superior to placebo, but the main underlying justification of a randomized controlled trial is that of clinical equipoise: the reason for doing the study is that there is "genuine uncertainty within the expert medical community - not necessarily on the part of the individual investigator" as to whether or not an intervention will work.Freedman] The new treatment might not be effective, and it might actually cause more harm than standard care or placebo. When the person enrolling individuals into a trial knows which group each individual will be assigned to, reported treatment effects have been shown to be exaggerated (more 'beneficial') by an average of 18% when compared to studies in which allocation was properly concealed (ratio of odds ratio 0.82, 95% CI 0.71-0.94) [Pildal, 2007].

//Other aspects of trial design:// In the episode, the allocation sequence is kept in envelopes. For this method, it is important to meet three key requirements: the envelopes should be 1) sealed, 2) opaque, and 3) sequentially numbered. While they were opaque and numbered, they were not sealed, allowing Meredith to see the assignment in advance. In modern trials, it is more likely that the randomization would be done centrally and the investigators would call in to receive the group assignment immediately before the procedure. Another safeguard is the use of coded group information. In the episode, the group assignments were actually spelled out on the page: intervention or placebo. If they had been labeled 'A' and 'B,' or had used some other method to hide the group assignment, it wouldn't have been as easy to switch the allocation. Since this was a surgical trial, it is likely that the surgeons would have been aware of the procedure following group allocation. While this might not be preventable, blinding the outcome assessors would be one way to minimize bias.

Story in the Los Angeles Times

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Examples
On this page we've compiled a number of examples of risk of bias assessments - the good, the bad, and those that are a bit unclear. Feel free to work through them yourself and come up with an assessment of **low **, **unclear ** , or **high ** risk of bias (our judgments and rationale are on the assessments page ), or download a spreadsheet file with the same information. RoB assessments are divided up into the seven major domains: sequence generation, allocation concelment, blinding of participants/personnel, blinding of outcome assessors, incomplete outcome data, selective outcome reporting, and other sources of bias. A quotation is given with the article title following in brackets.

If you have other examples, please add them to the list!

Risk of Bias Guidelines

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