From Gut Feeling to Data-Driven Decisions

The Evolution of Medical Risk-Benefit Analysis

RNfinity | 07-12-2024

Key Questions on Risk-Benefit Analysis in Medical Decision Making

1. What is benefit and risk analysis in healthcare?

Benefit and risk analysis in healthcare is a structured approach to evaluating the potential positive outcomes (benefits) against the potential negative outcomes (risks) of medical interventions or treatments. 

2. How is medical decision making influenced by risk-benefit assessment?

Medical decision making relies heavily on risk-benefit assessments to determine the most appropriate course of action for patient care, weighing potential benefits against potential risks of treatments or interventions. 

3. What are the benefits of risk assessment in healthcare?

Risk assessment in healthcare helps identify potential hazards, prioritize patient safety, improve treatment outcomes, and inform evidence-based decision making. 

4. How is informed decision making implemented in healthcare?

Informed decision making in healthcare involves providing patients with clear, comprehensive information about their condition, treatment options, and associated risks and benefits to enable them to make educated choices about their care. 

5. What role does risk and cost benefit analysis play in healthcare decisions?

Risk and cost benefit analysis helps healthcare providers and policymakers evaluate the economic implications of medical interventions alongside their clinical effectiveness and potential risks.  Key Concept: Risk-benefit analysis in medical decision making is a crucial process that involves systematically evaluating the potential positive and negative outcomes of healthcare interventions to inform treatment choices and policy decisions.


Early Approaches (1970s-1990s): The Era of Expert Opinion


In the early years, benefit-risk assessments were largely qualitative and often subjective. Regulators and healthcare professionals relied heavily on expert opinion and clinical judgment. This period was characterized by:


  1. Lack of standardized methods: There was no consistent approach to weighing benefits against risks.

  2. Limited quantitative data: Most assessments were based on qualitative observations rather than robust statistical analyses.

  3. Focus on individual case reports: Adverse events were often evaluated based on individual case reports rather than systematic reviews or meta-analyses.


One notable development during this period was the introduction of the "Kefauver-Harris Amendment" to the Federal Food, Drug, and Cosmetic Act in 1962. This amendment required drug manufacturers to provide proof of effectiveness and safety before approval, marking a significant shift in drug regulation.


Example study:

Temple, R. (1981). "Government viewpoint of clinical trials." Drug Information Journal, 15(1), 10-17.

This paper discussed the FDA's evolving approach to evaluating clinical trial data for drug approval, highlighting the challenges in balancing efficacy and safety.


Shift Towards Structure (Late 1990s-Early 2000s): The Rise of Evidence-Based Medicine


The late 1990s and early 2000s saw a growing recognition of the need for more structured approaches to benefit-risk assessment. Key developments included:


  1. Introduction of NNT and NNH: These concepts provided a more intuitive way to communicate benefits and risks to both healthcare professionals and patients.

  2. Emergence of evidence-based medicine: This movement emphasized the importance of using high-quality clinical evidence in decision-making.

  3. Development of systematic review methodologies: The Cochrane Collaboration, founded in 1993, played a crucial role in promoting systematic reviews and meta-analyses.


Example studies:

  1. Holden, W. L., Juhaeri, J., & Dai, W. (2003). "Benefit-risk analysis: a proposal using quantitative methods." Pharmacoepidemiology and Drug Safety, 12(7), 611-616.

  2. Sackett, D. L., Rosenberg, W. M., Gray, J. A., Haynes, R. B., & Richardson, W. S. (1996). "Evidence based medicine: what it is and what it isn't." BMJ, 312(7023), 71-72.


Emergence of Frameworks (Mid 2000s-2010s): Structuring the Decision-Making Process


This period saw the development of several structured frameworks for benefit-risk assessment:


BRAT Framework

The BRAT Framework, developed by PhRMA, includes six steps:


  1. Define decision context

  2. Identify outcomes

  3. Identify data sources

  4. Customize framework

  5. Assess outcome importance

  6. Display and interpret key benefit-risk metrics


Levitan, B. S., Andrews, E. B., Gilsenan, A., Ferguson, J., Noel, R. A., Coplan, P. M., & Mussen, F. (2011). "Application of the BRAT framework to case studies: observations and insights." Clinical Pharmacology & Therapeutics, 89(2), 217-224.


EMA Benefit-Risk Methodology Project

The EMA's project explored various methodologies for benefit-risk assessment, including:


  1. PrOACT-URL: A qualitative framework for structuring the decision-making process

  2. MCDA: A quantitative method for complex cases

  3. Stochastic Multicriteria Acceptability Analysis (SMAA): A method for dealing with uncertainty in MCDA


Hughes, D., Waddingham, E., Mt-Isa, S., Goginsky, A., Chan, E., Downey, G. F., ... & Micaleff, A. (2016). "Recommendations for benefit–risk assessment methodologies and visual representations." Pharmacoepidemiology and Drug Safety, 25(3), 251-262.


Adoption of Structured Approaches (2010s-Present): The Age of Quantitative Analysis


Recent years have seen increased adoption and refinement of structured benefit-risk assessment methods:


PROTECT Project

The PROTECT project, a collaboration between academia, regulatory authorities, and pharmaceutical companies, aimed to strengthen the monitoring of benefit-risk of medicines in Europe.


Mt-Isa, S., Hallgreen, C. E., Wang, N., Callréus, T., Genov, G., Hirsch, I., ... & Noel, R. (2014). "Balancing benefit and risk of medicines: a systematic review and classification of available methodologies." Pharmacoepidemiology and Drug Safety, 23(7), 667-678.


Quantitative Methods

MCDA has gained prominence as a quantitative method for benefit-risk assessment. It allows for the incorporation of multiple criteria and stakeholder preferences.


Tervonen, T., Naci, H., van Valkenhoef, G., Ades, A. E., Angelis, A., Hillege, H. L., & Postmus, D. (2015). "Applying multiple criteria decision analysis (MCDA) in the context of health technology assessment: an empirical case study." Value in Health, 18(7), A569.


Current State: Patient-Centered, Data-Driven Decision Making


The current state of benefit-risk assessment is characterized by:


  1. Integration of patient preferences: There's an increasing focus on incorporating patient perspectives into benefit-risk assessments.

  2. Use of real-world evidence: There's growing interest in using real-world data to complement clinical trial data in benefit-risk assessments.

  3. Refinement of existing methods: Researchers continue to refine and improve existing benefit-risk assessment methods.


Mühlbacher, A. C., Juhnke, C., Beyer, A. R., & Garner, S. (2016). "Patient-focused benefit-risk analysis to inform regulatory decisions: The European Union perspective." Value in Health, 19(6), 734-740.


Schneeweiss, S., Eichler, H. G., Garcia-Altes, A., Chinn, C., Eggimann, A. V., Garner, S., ... & Wang, J. (2016). "Real world data in adaptive biomedical innovation: a framework for generating evidence fit for decision-making." Clinical Pharmacology & Therapeutics, 100(6), 633-646.


In conclusion, the field of benefit-risk assessment has evolved significantly over the past 50 years, moving from largely qualitative and subjective approaches to more structured, quantitative, and patient-centered methods. This evolution reflects a growing recognition of the complexity of medical decision-making and the need for transparent, evidence-based approaches to evaluating the benefits and risks of medical interventions.


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