Regulators, industry tout new approach for benefits-risk assessments

BALTIMORE – Regulators and industry representatives said that a new international guideline for evaluating the benefit-risk profile of new and marketed drugs developed by the Council for International Organizations of Medical Sciences (CIOMS) is a major step forward in improving such assessments.

Beginning in 2019, CIOMS Working Group XII has met a dozen times to work on an update to the 1998 CIOMS IV document Benefit-Risk Balance for Marketed Drugs: Evaluation of Safety Signals. CIOMS XII released a draft report of the updated document for comment in June 2023.

The revision provides a more structured approach to conducting these assessments and a major change is the guideline calls for these assessments to be conducted throughout the product’s lifecycle. During a 6 February panel on Global Pharmacovigilance sponsored by the Drug Information Association, companies were also told to establish cross-functional teams to conduct these risk assessments.

Brian Edwards, vice president of the International Society of Pharmacovigilance, told the meeting attendees that the document is meant to be applied by regulators and industry worldwide.

New approach

Hong Yang, senior advisor for benefit-risk assessment in the Office of Biostatistics and Pharmacovigilance (OBP) within FDA’s Center for Drug Evaluation and Research (CDER) said the guide represents a new approach to conducting benefit-risk assessments. Yang was a member of the working group that developed the document.

She said that “much has changed” since the last update in 1998, when the CIOMS Working Group IV published its first report on the topic, according to the recent CIOMS newsletter. Since the last revision, products have become more complex, new data sources are now available for decision-making, new regulatory pathways have emerged, and the patient perspective is more prominently featured.

Yang said the highlights of the guide include a structured benefit risk-framework (SBR), which is a core part of the benefit-risk assessment (BRA). The SBR can be supported by additional quantitative analysis to justify decisions to approve complex products. The guide also espouses a lifecycle approach for BRAs starting from drug development to post marketing development.

The new guide also replaces the current “ad hoc” approach for conducting BRA assessments to an approach that more proactively incorporates the benefit risk analysis in designing the trial and collecting the data.

Richard Forshee, deputy director of OSB, who worked on the guide’s chapter on benefit-risk methodology considerations, offered his perspective on the guide. “Benefit-risk assessments have been at the heart of evaluating medicinal products for decades. It is one of the key decisions we have to make as regulatory bodies,” he told the group.

Forshee also stressed the importance of conducting the benefit-risk process early on to ensure that the right data is collected.

Susan Colilla, senior director, epidemiology lead at Teva Pharmaceuticals, said the company “championed” the principle of conducting benefit-risk assessments earlier in the drug development process.

Multidisciplinary teams

Forshee also advised companies to establish multidisciplinary teams in developing benefit-risk assessments. The team should include the product lead or the team leader, physicians, the pharmacovigilance scientist, the clinical team, the regulatory affairs team, clinical pharmacologists, toxicologists, the chemistry, manufacturing and control (CMC) team, and biostatisticians.

He said that “it is important to have a range of experience” in developing these risk assessments.” Colilla concurred. “We are encouraging our cross-functional colleagues to adopt this process.”

Forshee said these analyses can be useful in deciding whether to assign a higher risk for certain drugs. For example, Pfizer’s Comirnaty, the vaccine for COVID-19, was assigned a lower risk threshold as the product is administered in healthy adults and children with a lower chance, or a one in a million chance, of an adverse event occurring. Yet a gene therapy would have a much higher risk threshold because without these treatments, patients might have few alternatives to treat serious or life-threatening conditions.

CIOMS guide on benefit-risk analysis

Regulators, industry tout new approach for benefits-risk assessments

Related topics

Recommended content

Welcome to the new RAPS Digital Experience