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Chapter-8(A) Confirmatory Trials-Safety Data I
Introduction to…
Mayank
Chapter-8(A) Confirmatory Trials-Safety Data I
Introduction to Statistics in Pharmaceutical Clinical Trials
- Benefits associated with new treatment outweigh the risks. All drugs carry side-effects, some of which are more serious than others. Therefore, a drug to be approved, the regulatory agency needs to be presented with evidence of likely benefits to target population that outweigh the likely risks
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Adverse
Events
- Any untoward medical occurrence which does not have a causal relationship with the treatment
- Any unfavorable & unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product
Reporting AEs
- By study investigators on the basis of their own observations
- By the study participant as a self-reported event
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Absolute &
Relative Risks
- To do this in a standardized manner it is necessary to “code” the AE descriptions
- e.g., 25 participants received treatment A & 5 reported a headache, the proportion is 5/25 = 0.20, which can also be expressed as 20%
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- Only 1% of participants in placebo group reported dizziness compared with 3–4% of participants treated with the active drug.
- How might a regulatory reviewer interpret these data?
- The first conclusion is, dizziness was not reported very often, so, if drug is approved, most patients treated would probably not have a problem. However, the difference might generate some concern.
- Initially, absolute difference may not seem extreme. However, in relative terms, those treated with the investigational drug are 3 to 4 times as likely to experience dizziness. This measure of risk is called a relative risk
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Confidence intervals for
difference between 2 proportions
In this approach, we calculate a confidence interval about difference in proportions for two independent groups
Data
- 6 out of 98 participants in placebo group reported a headache & 25 out of 302 participants in combined active groups reported a headache
Analysis
- Step 1: Point estimate = 0.06-0.08=-0.02
- Step 2: Standard error =
- Step 3: Reliability factor - 1.96 and for this interval, we use continuity factor 0.5(1/98 + 1/302) = 0.007
- Step 4: Confidence interval -
Lower limit is -0.02-1.96(0.03)-0.007 = -0.09
Upper limit is -0.02+1.96(0.03)-0.007 = 0.04
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Standard Error
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Standard Error
Confidence interval for difference with Correctional Factor