Blinding procedures

This section contains the following:

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

Introduction

Blinding refers to keeping trial participants, health care providers, and sometimes those collecting and analysing clinical data unaware of the assigned intervention, so that they will not be influenced by that knowledge. Blinding is important to prevent bias at several stages of a controlled trial, although, it is not always possible to implement.

Blinding of patients is important because knowledge of group assignment may influence how they respond or perceive they respond to treatment. Patients who know that they have been assigned to receive the new treatment may either have favourable expectations or increased anxiety. Patients assigned to standard treatment may feel discriminated against or reassured that they are not being exposed to something new. Blinding is also used to protect against the possibility that knowledge of assignment may affect how health professionals behave (performance bias) or how the outcome is assessed (detection bias), however, blinding is not always practical (e.g. when comparing surgery to drug treatment).

Blinding is particularly important when outcome measures are subjective, such as patient’s assessment of pain. It is less important for objective criteria of outcome, such as death, when there is little scope for detection bias.

Authors should explicitly state who will be blinded and what steps will be taken to ensure blinding. Terminology such as single-blind, double-blind, or triple-blind should be avoided unless they are explicitly defined when writing a protocol because there are no agreed upon definitions for these terms.

Things to consider when writing a protocol

State who will be blinded (for example, participants, care providers, evaluators, monitors, or data-analysts).
Describe the mechanism of blinding (for example, capsules or tablets).
Describe the similarity of characteristics of treatments (for example, appearance, taste, and method of administration).
Explain why any participants, care providers, or evaluators will not be blinded.
Describe any mechanisms for unblinding the trial treatment i.e emergency code breaking.

Illustrative example - WHO pre-eclampsia trial

The study will be a multicentre randomized, placebo-controlled, double-blind trial.

There will be three chewable tablets containing 500 mg elemental calcium to be taken every day. Women will be instructed to chew tablets at meals, but at least 3 hours away from any iron supplements. The control group will receive three tablets a day of identical characteristics, colour and taste as the intervention tablet prepared and packed by the same pharmaceutical manufacturer.

The need for unblinding should be extremely rare as the trial intervention is not associated with severe side effects and it will not delay or prevent standard management of the patient in the case of a complication such as renal calculus. If the woman develops pre-eclampsia or eclampsia, she will be treated according to routine treatment protocols regardless of the supplementation status. If, however, unblinding is needed for any reason the trial coordinator in Geneva will be contacted to reveal the treatment. (WHO Multicentre Randomized Trial of Calcium Supplementation for the Prevention of Pre-eclampsia - go to protocol)

Illustrative example - Perinatal care trial

Given the nature of the intervention, we cannot blind the randomisation, and data collectors will know if they belong to an intervention/control hospital. Furthermore, intervention hospitals will receive a computer to implement the intervention, which will be used, among other things, to monitor clinical data (i.e., episiotomy rate and active management of the third stage of labour). As a consequence, it is expected that the intervention will improve the capacity of intervention hospitals to collect and review clinical data and bias might be introduced in outcome assessment. To minimize this problem, the data collection system will be isolated from the intervention instruments as much as possible. (CLAP Trial - go to protocol)

Illustrative example - From the BMJ

Clearly, the mothers recruited and the health educators were not blind to the assignment of mothers to different groups. The outcome assessors were always blind to the assignment at both the 3 and 6 month follow up visits. Staff who were involved in data collection at the 3 month follow up were not involved in data collection at 6 months. The data analysts were not blind to the coding of the groups. (BMJ 1998;316:805–11 - go to article (included with permission))

Additional resources

Checklist for interventions, follow-up and adherence

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.

Commercial Clinical Trial Supplies

There are companies dedicated to the preparation and packaging of clinical trial supplies. Services may include:

Filling, labelling and assembly of a wide range of packs
Complete Investigator Case assembly
Blinding of tablets and capsules and production of matching placebos
Blister packaging including printing on-line with texts in any language
Randomized labels and code break envelopes
Temperature controlled storage
Distribution of supplies to investigators

These can be found by searching the internet.