Throwback to picking teams for dodgeball...

We all remember standing and waiting to be picked for team sports. On purpose, teams are "rigged", we try to get the best players to give us an edge. Stacking your team with the best players is called Selection Bias. However, in a clinical trial, this will ruin your chances of getting at the truth!

• Investigators want to help, and want their studies to be successful, so they will try to give the patient the treatment they think is better - selection bias.

• We use a process called allocation concealment (AC) to prevent selection bias.

• Study designers use AC to make sure investigators cannot know, predict or manipulate the groups. AC is what ensures randomization creates groups that are prognostically equal. This applies to both known and unknown characteristics of the patients.

• Some papers mention doing AC, but they do not do it, or they are unclear on the process.

• Failure to do allocation concealment almost doubles the odds of having a positive result! This results in a high risk of bias or systematic errors.

• Understanding how AC works and learning the descriptions of the process is usually enough to see if they took the appropriate steps.

  
  

Allocation concealment is a process that takes place during enrolment for the study - between the random list generation and the creation of the different groups.

AC makes sure the investigator or person enrolling participants is not able to know, predict or manipulate which group each participant will belong to. It is the most important step to ensure the groups have similar prognosis. Failure to appropriately do it, leads to selection bias. Investigators might wait to select the perfect patient for the intervention under study. We all have conscious and unconscious biases and might, for benign or not so benign motives, want a patient to be in the new, fancy treatment group, as we hope to improve their outcomes.

By directing patients to particular groups, we nullify the superpower of randomization, which is to keep both known and unknown variables in each group similar. A study in 2005 looked at allocation concealment in RCTs from BMJ, JAMA, the Lancet and the New England Journal of Medicine. Trials included were published from January 2002 to December 2002. It showed that among the 234 trials that met the inclusion criteria, allocation concealment was adequate in 132 (56%) and inadequate in 41 (18%); in 61 (26%) the concealment method was unclear. The odds of a positive results were 1.8 (95% CI: 0.8 to 3.7), if the concealment was inadequate compared with a trial with adequate concealment. This suggests that trials using inadequate concealment tend to show significant differences between the groups in the primary outcome more often than trials using adequate concealment.1

 "For some implementing a trial, deciphering the allocation scheme might frequently become too great an intellectual challenge to resist. Whether their motives indicate innocent or pernicious intents, such tampering undermines the validity of a trial." 2.

When appraising the literature, many studies that mention allocation concealment have actually not done it, as shown in the study above. A description of the process is always more helpful to understand if it really happened or not.

In multicenter trials, allocation concealment is usually done by calling a centralized number once a patient meets inclusion criteria. A recording with a group assignment is then played or a person assigns the group. The investigator has no access to the list for enrollment and cannot know the next assignment. Sometimes we can guess which group the next patient will belong to, if we know that randomization was done in blocks of a certain size. A way to avoid this, is generating randomization lists with random-sized blocks. That will make it impossible to predict which group the next patient will belong to.

In single center trials, in which the team knows each other and might have access to the list, this might be harder. But following similar steps, such as creating a list with random blocks and then placing assignments in opaque envelopes can achieve the same goal.

So from now on, make sure you look at the methods! It is one of the best protections you have against biased results!

1. Hewitt C, Hahn S, Torgerson D J, Watson J, Bland J M. Adequacy and reporting of allocation concealment: review of recent trials published in four general medical journals BMJ 2005; 330 :1057 doi:10.1136/bmj.38413.576713.AE

2. Schulz KF, Grimes DA. Allocation concealment in randomized trials: defending against deciphering. The Lancet. 2002;359(9306):614-618.