Statistics 1991

Write short notes on bias in drug trials and how its influence may be reduced.
Bias - A systematic deviation from the truth
In a study the observed difference may be as a result of
- Treatment effect (true difference),
- Random variation (chance) or
- Deficiency in the research design which enabled systematic differences (bias) to exist in either the:
o Group characteristics
o Measurement
o Data collection or
o Analysis

1. Selection Bias: Where group allocation leads to a spurious improved outcome because one group is healthier
or at lower risk than another
- Example: comparing groups from different hospitals where one may treat a less well community.
- Reduction: true randomisation, where group allocation is determined by chance and preferably not by the
researcher

2. Detection Bias: Where measurements or observations in one group are not as vigilantly sought as in the other
- Example: being lazy collecting survey results from patients known to be in control group of BIS trial
- Reduction: blinding of observer such that individuals are assessed equally

3. Observer Bias: Where the person responsible for data collection is able to use judgement as to whether an
event occurred or not, or determine its extent
- Example: deciding that a patient in the BIS trial who reported hearing voices wasn’t really ‘aware’ during
anaesthesia
- Reduction: clear definition of end points to minimise the need for judgement calls. Well defined scales e.g.
VAS to determine extent of an effect or symptom

4. Reporting Bias (or recall bias): Where a person’s group identity influences their likelihood of accurately
reporting previous symptoms, experiences or outcome
- Example: knowing you are a human guinea pig for a new drug may lead to hyper awareness of symptoms
- Reduction: randomisation and blinding to prevent patients’ knowledge of group allocation

5. Response Bias: Where patients who enrol in a trial differ from those in the population of interest (and so the
results may not be generally applicable)
- Example: people who reply to political phone polls are lazy dole bludgers sitting at home by the telephone
during the day when everyone else is at work. Alternatively, payment for trial participation generates
response bias
- Reduction: multi-centre trials broaden the ‘net’ and may involve a spectrum of individuals who better
represent the population. Non payment. Compulsory enrolment of eligible subjects – easier in a
retrospective study where no

6. Publication Bias Where negative studies are less likely to be submitted or accepted for pub.
- Example: NEJM likes positive results
- Reduction: Choose a better editorial committee who accept or decline articles for publication based on
clearly defined, fair and relevant criteria

7. The Hawthorne Effect: Where the actual process of participating in a study may alter the outcome in such
patients.
- Example: group randomised to naturopathy may benefit from counselling and extended consultation
- Reduction: low impact studies, equal involvement in both control and treatment groups

8. Migration Bias: Patients dropping out of the study are dropped from the analysis

Natalie JohnstonDavid Bramley Page 1 August 10, 2021

 Statistics 1991
Minimising Bias: Randomisation and blinding are the two most important factors to reduce bias in trial design

Natalie JohnstonDavid Bramley Page 2 August 10, 2021