Lecture 7: Pharmacoepidemiology: risk-benefit analysis and meta analysis

Question 1

Introduction to Risk Benefit Assessment (RBA)

Answer 1

Risk and benefit assessment monitoring are significant contributors to promoting safety and quality in the delivery of health care

Question 2

RBA (What is it?)

Answer 2

Quantitative methods for systematically evaluating the risks and benefits of new or existing medical interventions

Question 3

RBA (Why?)

Answer 3

These methods evaluate risk-benefit tradeoffs to assist regulatory and clinical decision making in the absence of directly comparable metrics

Question 4

RBA (Who?)

Answer 4

Regulators, clinicians and patients who routinely make decisions that require trading safety for desired clinical benefits

Question 5

Benefits

Answer 5

-any favorable outcome of the research to society or to the individual

Question 6

Risks

Answer 6

-refers both to the probability of a harm resulting from an activity and also to its magnitude (its HR, IRR, AEs)

Question 7

Challenges of RBA

Answer 7

• Heterogeneity of metrics (few common denominators)
• Multiplicity (multiple benefits and risks)
• Uncertainty (temporality)
• Paucity of data (exposure: patients and time distribution and outcomes)

Question 8

Some metrics of RBA

Answer 8

-NNT, QALYs (quality of life)

Question 9

Risk Management

Answer 9

1) Risk identification
2) Risk assessment
3) Risk prioritization and communication (improve collective and individual decision making)

Question 10

Current approaches to RBA

Answer 10

-there is no single approach to RBA, so regulatory bodies in the US and abroad are looking for ways to standardize it

Question 11

Problem states in RBA

Answer 11

• development strategies (when does increased benefit outweigh potential increased risk)
• regulatory approval (how do you know if risk outweighs benefit?)
• risk management (when do you require risk/benefit plans)

Question 12

Quantitative Approches and Techniques for RBA

Answer 12

1) Quantitative framework for risk and benefit assessment (QFRBA)
2) Beneft-less risk analysis (BLRA)
3) Quality adjusted time without symptoms and toxicity (Q-TWIST)
4) Number needed to treat (NNT) vs. Number Needed to Harm (NNH)
5) Relative Value adjusted number needed to treat (RV-NNT)
6) Minimum Clinical Efficacy (MCE)
7) Incremental Net Health Benefit (INHB)
8) Risk Benefit Plane (RBP) and Risk Benefit Acceptability Threshold (RBAT)
9) Probabilistic Simulation Methods (PSM)
10) Multi-Criteria Decision Analysis (MCDA)
11) Risk-Benefit Contour (RBC)

Question 13

RBA Framework

Answer 13

Measure background benefit, characterize background risk, design study, analyze relative risk benefit, communicate risk benefit to FDA all to optimize risk benefit of drug of interest

Question 14

Optimizing benefit-risk profile

Answer 14

demonstrate product benefit, characterize risk, quantify the benefit/risk, ensure appropriate use and communicate benefit/risk to stakeholders

Question 15

Conclusions

Answer 15

• Quantitative RBA and meta-analytic methods supplement, but do not replace the existing paradigms used by regulators and researchers
• New methods should be mathematically sound, involve relatively straight-forward computations and enhance the scientific validity of the current RB assessment
• multiple RBA techniques may be developed to triangulate the risk benefit profile of a product

Question 16

Points to Consider

Answer 16

• Deploy RBA as a continuous feedback cycle starting early in clinical development
• engage stakeholders to better understand and participate in RBA
• focus on the patient perspective when appraising risk-benefit