• Appendix

Benefit Risk Assessment

Benefit risk assessment is a vital part of the activities of any pharmacovigilance entity. Every drug or medicinal product is bound to have positive and negative effects, some of which may not be detected until they have been released into the market.

How we define “Benefits” or “Risks” varies immensely and is highly contextual. Generally, we expect “Benefits” to contribute to an individual’s wellbeing, whiles risk poses harm. Once ADRs are detected, it is important that a regulatory authority makes a decision based on scientific evaluation of the benefits and/or harms. It is a truly complex activity which requires evaluation of a large amount of data to ensure that the benefits outweigh the risks, upon this premise a drug can authorised for marketing or not. Ideally, greater risk can be acceptable if the disease is fatal and there is a chance of cure by using the treatment. However, we can only accept little risk if the disease has a good outcome without the treatment, or if these are essential medicines given to healthy people such as vaccines and oral contraceptives.

The decision on making the right balance between effectiveness and risk is not straightforward. Indeed many authorities use different methods to regulate the system. According to the Council for International Organizations of Medical Sciences (CIOMS), “it is a frustrating aspect of benefit risk evaluation that there is no defined and tested algorithm or summary metric that combines benefit and risk data and that might permit straightforward quantitative comparisons of different treatment options, which in turn might aid in decision making”.

Models used for benefit risk balance

In trying to shed more light on the issue, the European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) provided a report on the various benefit-risk assessment models and methods. The report described 2 types of models; mainly for individual clinical trials, and general models.

Number Needed to Treat to Number Needed to Harm

For individual clinical trials, it is possible to use the ratio of Number Needed to Treat to Number Needed to Harm (NNT/NNH) which is also mostly used in HTA assessments.

  • NNT: Number of patients who need to be treated to prevent one additional adverse outcome
  • NNH: Number of patients to be treated before one experience of an adverse treatment related outcome.

Other general models include

Principle of Threes

“The Principle of Threes” proposed by Edwards et al., in 1996 is a method which explores the paradigms of Seriousness, Duration and Incidence with respect to the

  • Disease
  • Improvement produced by the drug
  • Adverse effects of the drug

These various paradigms can be described using the terms below:

Other General Models

These other models use quantitative and graphical approaches and complex algorithms to conduct benefit risk assessment. They include

  • Multi criteria decision analysis (MCDA)
  • The TURBO (“Transparent Uniform Risk Benefit Overview”) model

You can read more about all these models in the CIOMS Working Group IV Report on Benefit-Risk Balance for Marketed Drugs: Evaluating Safety Signals

Or watch this educative video from the Uppsala Monitoring Centre:

Ultimately none of these methods are cut in stone, and for any regulatory body, it is important to ask the essential questions, obtain the necessary data and evaluate a safety concern using the appropriate benefit risk assessment method. Benefit Risk Assessment is highly dependent on the environment. If your country has a solid pharmacovigilance system in place, it is possible to explore the methods discussed above.

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