State-of-the-Art Workshop: complex risk-benefit analysis

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Randomised Controlled Trials (RCT) are the “gold standard” for the assessment of comparative clinical effectiveness of health technologies and an important method for collecting economic data. The use of RCTs is critical to inform policy decisions to ensure that effective health technologies are adopted into current practice. In order to make these policy decisions, information is needed on multiple aspects of the treatment, this includes the effectiveness of the primary health outcome, safety and cost. This multi-dimensional approach to decision making reflects that taken by patients in practice when offered different treatment choices. Often, a new treatment will not improve all three of these elements and therefore a benefit-risk assessment (BRA) is required to evaluate the net clinical benefit of the new treatment and whether this is worth implementing in practice.

This evaluation occurs often within the pharmaceutical industry where regulators weigh up the benefits of a drug against its harms. However, to extend this to the health technology setting, it is important that costs are also considered. When testing against treatments already in current practice we could be asking “what level of clinical outcome is acceptable to be lost for a reduction in side effects/costs?” Such an evaluation can be carried out using a BRA which has the benefit of being weighted for patient preference of the trade-off available for example the acceptable of less benefit for less harm.

There are some signs that recent work in this area has begun to influence practice. However, guidance is limited and does not fully meet the needs of funders and researchers.

The overall aim of this study is to provide consensus-driven guidelines for the trial design for superiority and non-inferiority trials. The specific objectives are to:

1. Provide guidance on when it is appropriate to use superiority and non-inferiority trial designs,
2. Critically evaluate the methods of BRA appropriate for both superiority and non-inferiority,
3. Provide guidance on which methods of BRA are most appropriate for superiority and non-inferiority trial to provide optimal trial design