Error/Bais in Rsearch Methodology and Pharmaceutical Statistics . A biased estimate is one which, on the average, does not equal the population parameter.

1. Error/Bias
Name- Akash Singh
Assistant Researcher
Institute of Pharmacy
Harish Chandra P.G College Varanasi

2. Bias-
“A systematic error (caused by the investigator or the subjects) that causes an incorrect (over- or under-) estimate of an
association”.
 Bias is defined as any tendency which prevents unprejudiced consideration of a question.
 In research, bias occurs when “systematic error is introduced into sampling or testing by selecting or encouraging one outcome
or answer over others”.
 Bias can occur at any phase of research, including study design or data collection, as well as in the process of data analysis and
publication.

4. Pre-trial bias-
 Sources of pre-trial bias include errors -
1. In study design
2. In patient recruitment.
Type-
 Flawed study design
 Selection bias
 Channeling bias
1. flawed study design- errors can cause fatal flaws in the data which cannot be compensated during data analysis.

5. 2- Selection bias- Selection bias may occur during identification of the study population.
•The ideal study population is clearly defined-
 accessible
 Reliable
 at increased risk to develop the outcome of interest.
“Selection bias can cause an overestimate or underestimate of the association”

6. Selection bias can occur in several ways –
1. Selection of a comparison group ("controls") that is not representative of the population that produced the cases in
a case-control study. (Control selection bias)
2. Differential loss to follow up in a cohort study, such that the likelihood of being lost to follow up is related to
outcome status and exposure status. (Loss to follow-up bias)
3. Refusal, non-response, or agreement to participate that is related to the exposure and disease (Self-selection bias)
4. Using the general population as a comparison group for an occupational cohort study ("Healthy worker" effect).
Selection bias can occur in a case-control study if controls are more (or less) likely to be selected if they have the
exposure”.
3- Channeling bias- These occurs when patient prognostic factors or degree of illness dictates the study
cohort into which patients are placed.
 This bias is more likely in non-randomized trials when patient assignment to groups is performed by medical
personnel.
 Channeling bias is commonly seen in pharmaceutical trials comparing old and new drugs to one another .

8. Bias during the clinical trial -
1. Information bias –Systematic errors due to incorrect categorization.
Subtype of information bias
 Interviewer bias
 Chronology bias
 Recall bias
 Patient loss to follow-up
 Bias from misclassification of patients
 Performance bias

9. Interviewer bias-
 Interviewer bias refers to a systematic difference between how information is solicited, recorded, or interpreted .
 Interviewer bias is more likely when disease status is known to interviewer.
Minimized by:
 Blinding the interviewers if possible.
 Using standardized questionnaires consisting of closed-end, easy to understand questions with appropriate response
options.
 Training all interviewers to adhere to the question and answer format strictly, with the same degree of questioning for
both cases and controls.
 Obtaining data or verifying data by examining pre-existing records (e.g., medical records or employment records) or
assessing biomarkers

10. Chronology bias-
 Chronology bias occurs when historic controls are used as a comparison group for patients undergoing an intervention.
For example- many micro surgeons currently use preoperative imaging to guide perforator flap dissection. Imaging has been
shown to significantly reduce operative time.
Minimize by-
 conducting prospective cohort
or
 randomized control trials,
or
 by using historic controls from only the very recent past.

11. Recall bias-
 Recall bias refers to the phenomenon in which the outcomes of treatment (good or bad) may color subjects' recollections
of events prior to or during the treatment process.
Example-the perceived association between autism and the MMR vaccine. This vaccine is given to children during a
prominent period of language and social development.
 Recall bias is most likely when exposure and disease status are both known at time of study.
 It can also be problematic when patient interviews (or subjective assessments) are used as a primary data source.
To Minimize:
 Use a control group that has a different disease (unrelated to the disease under study).
 Use questionnaires that are constructed to maximize accuracy and completeness. Ask specific
questions. More accuracy means fewer differences.
 For socially sensitive questions, such as alcohol and drug use or sexual behaviors, use a self-
administered questionnaire instead of an interviewer.
 If possible, assess past exposures from biomarkers or from pre-existing records.

12. Performance bias -
 In surgical trials, performance bias may complicate efforts to establish a cause-effect relationship between procedures and
outcomes.
 To minimize or avoid performance bias-
Iinvestigators can consider cluster stratification of patients, in which all patients having an operation by one surgeon or at one
hospital are placed into the same study group, as opposed to placing individual patients into groups.

13. Transfer bias -
 Transfer bias can occur when study cohorts have unequal losses to follow-up.
 Some authors suggest that patient loss to follow-up can be minimized by –
 offering convenient office hours
 personalized patient contact via phone or email
 physician visits to the patient's home

14. Bias after a trial-
 conclusion can occur during data analysis or publication.
1. Citation bias
2. Confounding
Citation bias- Citation bias refers to the fact that
 researchers and trial sponsors may be unwilling to publish unfavorable results,
 believing that such findings may negatively reflect on their personal abilities or on the efficacy of their product.

15. Confounding-
Confounding occurs when an observed association is due to three factors:
 the exposure
 the outcome of interest
 and a third factor which is independently associated with both the beoutcome of interest and the exposure.

16. Avoid-

17. References-
 Kothari, C.R. (2019) Research Methodology: Methods and Techniques. 4th Edition, New Age International Publishers,
New Delhi.
 Ana-Maria Šimundić,University Department of Chemistry, University Hospital Center “Sestre Milosrdnice”, Zagreb,
Croatia.
 Bolton, S., & Bon, C. (2009). Pharmaceutical Statistics (5th ed.). CRC Press. Retrieved from
https://www.perlego.com/book/1599493/pharmaceutical-statistics-practical-and-clinical-applications-fifth-edition-pdf
(Original work published 2009)
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