BIAS AND ITS CONTROL IN RANDOMISED CLINICAL TRIALS

 

BIAS AND ITS CONTROL IN RANDOMISED CLINICAL TRIALS

 BIAS - Any repeatable error in the study design, conduct, or analysis of a study that encourages one outcome over others. The disadvantage of bias is investigators will come to the wrong conclusions about the beneficial and harmful effects of medication.

HOW DOES BIAS EFFECT RESEARCH?

  Bias in research can lead to wrong conclusions. Such studies can result in wrong clinical practice and they can sometimes cause harm to the patient.

TYPES OF BIAS IN CLINICAL TRIALS-

•       Selection bias –It is an experimental error that happens when the participant pool data is not representative of the target population.

•       Performance Bias - may occur by both the researcher as well as the participant due to the knowledge on the  allocation

•       Detection bias –means systematic differences between groups in which outcomes are determined.

•       Attrition bias – A type of selection bias that results from changes in the experimental result between study groups in the number and the way participants are lost from the study.

•       Reporting bias – Occurs when dissemination is influenced by the nature and direction of results, for instance in systematic reviews.

HOW TO MINIMISE BIAS IN CLINICAL TRIALS-

  Bias can be minimized by using masking or blinding which means one or more parties like the subject, investigator, the sponsor is unaware of the treatment drug and these studies are designed to avoid bias.

SOURCES OF BIAS-

•       Investigator

•       Participant

•       Literature

•       Statistician

•       Instruments

WHERE BIAS CAN HAPPEN- Bias can arise at three steps of the study

1. During initial enrolment of the participants
2. During the implementation of the study
3. During the analysis of findings.

HOW TO AVOID BIAS IN RESEARCH?

•       Use multiple people to code data

•       Verify the data with more sources

•       Check for other explanations

•       Review findings

•       Use third-person opinion

WHY SHOULD BIAS AVOIDED IN RESEARCH-

    Bias can result in a false conclusion and giving the wrong idea or impression. Therefore it is not acceptable to conduct research. 

TECHNIQUES TO AVOID BIAS –

1. The randomization of subjects.
2. Double blinding of subjects as well as investigator.
3. Monitoring clinical trial.
4. Checking source documents.
5. Verification of source documents.
6. Clinical data management.
7. Procedures of quality control and assurance.

 

RANDOMISATION – Process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments to reduce the bias.

WHY RANDOMISATION?

•       To ensure comparability of the two arms regarding known and unknown factors.

•       Avoid selection bias.

•       3. Helps to design standard statistical analysis

•       To increase the predictive value of the study.

TYPES OF RANDOMISATION-

•       Simple randomization

•       Block randomization

•       Stratified block randomization

•       Unequal randomization

SIMPLE RANDOMISATION –

•       The basic method of simple randomization is flipping a coin.

•       Computer-generated sequence.

•       The randomization approach is simple and easy to implement in clinical research.

•       In large clinical research, i.e., (n  simple randomization can be applied to generate similar numbers of subjects among groups.

•       However, randomization results could be problematic in small sample size i.e.,(n˂100) clinical research, resulting in an unequal number of participants among groups.

BLOCK RANDOMISATION-

•       The block randomization method is intended to randomize subjects into groups that end in equal sample sizes.

•       Used for small studies to maintain a good balance among groups.

STRATIFIED BLOCK RANDOMISATION-

•       The stratified randomization requires the need to control and balance the influence of covariates.

•       Typical examples of such factors are age group, the severity of the condition, and treatment center.

UNEQUAL RANDOMISATION-

When two or more treatments under evaluation have a price difference. The Substantial cost savings can be achieved by adapting a smaller randomization ratio such as a ratio of 2:1, with only a modest loss in statistical power.

CONCLUSION-

The benefits of randomization are numerous. The use of online randomization was effectively demonstrated in this article for benefit of researchers. Simple randomization works well for giant clinical trials and for tiny to moderate clinical trials without covariates, the utilization of block randomization helps to attain the balance. For small to moderate size clinical trials i.e.,( n˃100) with several prognostic factors or covariates, the adaptive randomization method could be more useful in providing a means to achieve treatment balance.

-By

K. Bindu Priya

R. Rikitha

Students at Clinosol research pvt ltd.