Rosemarie Bernabe, PhD Julius Center for Health Sciences and Primary Care Patient representatives’ contributions to the benefit-risk assessment tasks of the European Medicines Agency

EU Roadmap to 2015 Patients are said to contribute to benefit/risk considerations by “enrich(ing) regulatory decisions by complementing them with the views of those directly affected by regulatory decisions”

How to achieve a more structured involvement of patients in regulatory work?

Objective Provide a preliminary exploration of the thoughts of EMA committee members on the role of patient representatives in the assessment of benefits and risks of scientific committees.

Methodology 15 current or former EMA scientific committee member : 10 are scientists, 5 are patient representatives average committee experience being 4.9 years. Average EMA participation was 5.7 years 7 female, 8 male Analysis: Grounded Theory Risk studies framework

Risk-benefit Assessment 1.R/B Analysis: express risk (and benefit)’ in a benefit–risk picture 2.R/B Evaluation: determine benefit and risk significance 3.Risk Treatment: modifying risk 4.Decision making

On the contribution of patients in R/B in general Patient representatives bring in something new or original to the discussion. One regulator called this original contribution the ‘non- medical aspect,’ i.e. that aspect that is meta-medical (beyond what is strictly ‘medical’) and meta-scientific (beyond what is strictly ‘scientific’).

1. R/B Analysis “In respect to benefits we consider the obvious things... duration, the generalizability of the evidence of efficacy, alternative treatment, all kinds of things. On the risk side we also consider clinical importance, the nature of the toxicity, predictability, reversibility...” [B,B]

Cont. R/B Analysis Patient participants as providing an experiential picture of the pathology in question: “I mean you have the broader view of the pathology when you talk with patient representatives because when you get out of the clinics, you have a different view, you find that it is important talking with patients.” [B,A]

Cont. R/B Analysis Aspects that regulators would probably consider as negligible: “I suppose the patient perspective is important in that context because some of the side effects that may not seem as risk drivers might be actually important in terms of the impact on the patient and certain impact on patient compliance and willingness to use a medicine” [B,B]

Cont. R/B Analysis Thus, these meta-medical aspects, combined with the aspects that regulators generally consider as necessary, form part of the benefit–risk picture that scientific committees look at.

2. R/B Evaluation It is the majority opinion that patient representatives rightfully ought to go beyond the task of being information providers and consultants.

Cont. R/B evaluation For the majority of the participants, patient representatives allow for a specific and concrete understanding of risks and benefits. “If you’re a pathologist or a statistician or you know, a regulatory professional, you can calculate, you can look at the numbers, you can work out whether you think this is a sensible scientific rationale. What you can’t do in the same way is say, yeah but how important is it? How significant is it?” [A,B]

Cont. R/B evaluation “Another typical question is when there is a quality of life score, which is more of a subjective score, then one could ask the patients if this makes sense in the way that it is assessed and evaluated, and also if this is relevant from the kind of symptoms that are put there.” [B,B]

Cont. R/B evaluation “In those kinds of cases, we brought in these patients and asked, what does it mean, what is the difference for you if you could walk 20 m or 40 m? And then all of a sudden this stupid 20 m which for you and for me would make no difference at all, does make the difference, because it means you can reach your car, and by reaching your car you can drive to wherever you want. You can drive to your work, or maybe also, by walking 40 m you can reach your office and you can do your job.” [A,B]

Cont. R/B evaluation Appreciation of the significance of the benefits and the significance of adverse events and the uncertainties. Aid in providing a concrete basis for the values and weights given to specific benefits and risks.

3. Decision making In coming up with a consensus or a decision especially during moments of uncertainty: “Are we clear what the correct action to take, and of course we might want to change behavior, but if there is uncertainty, if we’re not clear as to what’s the best action for every individual out there, well then I think that’s a situation where we really need to get the input of patients, to explain to us what the patients’ values and judgments might be, how that might impact individuals and decisions…” [B,B]

Cont. Decision making When risks and benefits are high, the concrete expression of the patient perspective as the focal point in decision making At this point, regulators want some proof that their decision is, indeed ‘consistent with the patients’ judgment’ [B,B].

Cont. Decision making In moments of regulatory uncertainty, acceptable risk for patient participants becomes one of the elements not only to make the decision but to be confident about it: “I think the patient representative’s role in the committee is to kind of give the regulatory professionals who are there from national competent authorities or other interested groups, you know the commission, the agency whatever, give those people the confidence to be able to make a judgment whether there is probably a significant degree of uncertainty” [A,B].

Conclusion

Cont. Conclusion Necessity of their contribution is strongly felt when: both benefits and risks are high benefits are almost equal or are equal to risks when both benefits and risks are low Benefits Risks