Methods for concealment of allocation

This section contains the following:

Introduction
Things to consider when writing a protocol
Illustrative examples - WHO Pre-eclampsia trial
Illustrative examples - from the BMJ
Additional resources
Further reading

Introduction

Allocation concealment is the process that prevents any trial participant or investigator from knowing in advance the treatment to which subjects will be assigned. It is important that the decision to enrol a participant is made in ignorance of the treatment to which they will be assigned, as this knowledge may influence the decision on whether or not to enroll.

Allocation concealment should not be confused with blinding . Allocation concealment seeks to prevent selection bias (subjects with different characteristics being entered into the different groups). In contrast, blinding seeks to prevent performance and ascertainment bias (different response to treatment, or to measuring effect of treatment due to knowledge of which treatment was received).

Independent or "third-party" assignment is especially desirable and many good approaches to allocation concealment incorporate external involvement. Use of a central telephone randomization system is a common technique and automated assignment systems are likely to become more common. When external involvement is not feasible, a good method of allocation concealment is the use of sealed numbered containers. The interventions (often medicines) are sealed in sequentially numbered identical containers according to the allocation sequence. Enclosing assignments in sequentially numbered, opaque, sealed envelopes can also be a good allocation concealment mechanism if it is developed and monitored diligently. Investigators should ensure that the containers/envelopes are opened sequentially and only after the participant's name and other details are written on the appropriate label/envelope. Other adequate methods of allocation concealment include on-site computer systems, where allocations are held in a locked unreadable electronic file.

Things to consider when writing a protocol

Describe the method for concealment of allocation.
Describe how the randomisation sequence will be concealed until interventions are assigned.

Illustrative example - WHO Pre-eclampsia trial

Random allocation technique consists of allocating consecutively numbered treatment boxes for each woman, including in each box seven independent bottles, each of them with tablets for four weeks of treatment. Each bottle contains 100 tablets. Therefore each subject will have seven bottles with the same randomization number. Treatment boxes will be kept at the clinic. Bottles will be provided consecutively as needed every month after randomization. When the woman comes for antenatal care, she will return the used bottle from the previous month and will be given the next month's bottle from her box. She will return the bottle after 4 weeks, regardless of whether she finished the tablets or not. Each bottle is numbered from 1 to 7 within the box and should be used sequentially. (WHO Multicentre Randomized Trial of Calcium Supplementation for the Prevention of Pre-eclampsia - go to protocol)

Illustrative example - From the BMJ

The zinc and placebo syrups will be supplied in bottles that looked identical, and the appearance and consistency of the syrups will be similar. Vitamin A and placebo capsules will be identical in appearance. The randomisation code will be kept sealed until the completion of the study. The treatment allocations will be disclosed after the final analysis. ( BMJ 2001;323:314–8 - go to article (included with permission))

Additional resources

Allocation Checklist

This checklist has been contributed by Dave Sackett, who prepared it for the forthcoming 3rd edition of Clinical Epidemiology; A Basic Science for Answering Questions about Health Care, to be published by Lippincott, Williams & Wilkins in 2005.

Allocation text from 3rd edition of Clinical Epidemiology

This text has been contributed by Dave Sackett, who prepared it for the forthcoming 3rd edition of Clinical Epidemiology; A Basic Science for Answering Questions about Health Care, to be published by Lippincott, Williams & Wilkins in 2005.

Directory of randomisation software and services

This is a directory of randomisation software and services for clinical trials, including both simple do-it-yourself software and 24 hour telephone randomisation services. It is intended to help people planning and seeking funding for clinical trials.

Commercial randomisation services

There are services available which provide 24-hour automated telephone randomisation. However, these services are not free so you must agree their involvement before applying for your grant. These can be found by searching the Internet.