The Biotechnology Industry Organization (BIO) represents biotechnology companies, academic institutions, state biotechnology centers and related organizations throughout the United States and in many other countries. BIO members are committed to the discovery, development and delivery of new, novel treatments that promise to save lives or improve the quality of life. BIO member companies engaged in drug development believe that their fundamental responsibility to the patients they serve is to provide safe and effective products to meet unmet medical needs.
BIO has long advocated that patients and physicians need timely, accurate, and relevant information about the benefits and risks of a drug or biologic so that they can make well-informed choices about therapies. Such information also includes understanding of how companies approach benefit-risk questions. In deliberating the ethical dimensions of benefit-risk throughout a drug product’s lifecycle, the BIO Board Standing Committee on Bioethics developed a series of “Points to Consider” for member companies and stakeholders confronting these issues to further inform decision-making.
Points to Consider
1. All drugs and biologics carry both benefits and risks.
All drugs and biologics carry both benefits and risks, and benefits and risks must be considered together. Drug safety is not an absolute, but rather a matter of balancing demonstrated benefits against known risks. A product is considered safe if it has an appropriate benefit-risk balance for the intended population and use.
2. Meaningful and informed benefit-risk calibration requires agreement on the parameters and definitions of risk, and risk tolerance, in relation to the condition the drug is intended to treat or prevent.
The safety of a drug is assessed by determining whether its benefits outweigh its risks. Such assessments take into account not only clinical data regarding safety and effectiveness, but also other factors such as the nature and severity of the condition the drug is intended to treat or prevent, the benefits and risks of other available therapies for the condition, and the availability of risk management tools.
Variations in clinical and scientific judgment can lead to differing individual opinions and conclusions regarding a benefit-risk assessment despite agreement on a set of facts regarding the benefits and risks of a drug. Some of this variation in opinion about drug benefits and risks is the inevitable result of healthy public debate. However, general agreement on the parameters and definitions of risk and risk tolerance in relation to the condition the drug is intended to treat or prevent can limit variations in subjective judgment during the drug approval process, spur drug development, and better assist patients and providers as they make informed medical decisions.
3. Benefit-risk assessment demands integrity of process and data analysis alongside express acknowledgement of our limited ability to provide complete answers to all questions.
Benefit-risk requires balancing several factors, and that balance is only as reliable as the data collection and analysis process are robust, secure, and transparent. Moreover, a true and meaningful understanding of benefit-risk requires recognition, understanding, and communication of our limited ability to answer all questions.
Regulatory bodies are responsible for disseminating information that is well-substantiated and can effectively guide patient care; dissemination of information about benefits and risks that are very remote and hypothetical may only serve to mislead. Patients and doctors must receive the information about benefits and risks that is available and necessary for them to make informed and meaningful decisions, and interpret this information with the understanding that not all risks (or benefits) may be known.
4. Benefit-risk calibration during drug development should be discussed in relation to a product’s regulatory approval pathway.
While the legal standards for drug approval always remain the same, a variety of pathways to Food and Drug Administration (FDA) approval are available, based on the latest science and medical need. Some of these pathways are intended to expedite the approval process, and thus get important treatments and cures to patients more quickly. The benefit-risk calibration must be understood within the context of a product’s specific approval pathway.
The accelerated approval pathway, for example, permits approval based on a drug’s effect on a surrogate or clinical endpoint that is “reasonably likely to predict” clinical benefit. This effect must be deemed “clinically meaningful and of such importance as to outweigh the risks of treatment”. The additional measure of uncertainty in the data is incorporated as an additional factor in the benefit-risk calculus, and thus the product, once approved, is considered to have met FDA’s standards for safety and effectiveness in full.
5. Benefit-risk assessment continues after drug approval and is an ongoing enterprise throughout a product’s lifecycle.
Benefit-risk assessment does not end with product approval. Once a drug is approved and marketed, information is gained as the drug is used and studied in broader and more diverse populations. This additional information may inform our understanding of both benefit and risk. A lifecycle approach to risk-benefit requires not only recalibration and assessment, but also the communication of findings in a manner that respects context and audience in order to provide patients and providers with the tools necessary to make informed and meaningful medical decisions.
Further information about the BIO Bioethics Committee and its work can be found at http://www.bio.org/category/bioethics.