Guidance On Harmonization Of Patient-Focused Drug Development Is Years Away
Executive Summary
The International Council for Harmonization has proposed topics for a global PFDD guideline and is expected to begin work on it in the next few years. When finalized, the US FDA will issue it as draft guidance.
The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) has taken initial steps to develop a global approach to collecting and incorporating patient input in drug development and regulatory decision making. But it will take years for regulators and industry representatives from around the world to reach consensus on a harmonized guideline.
The ICH issued a reflection paper on patient-focused drug development in 2020. The document identified key areas where incorporating patient perspectives could improve the quality, relevance, safety and efficiency of drug development and inform regulatory decision making.
The ICH Assembly endorsed the paper and sought stakeholder comments through 7 March 2021. Based on feedback from the public consultation, the reflection paper was revised and endorsed by the ICH Assembly in June 2021. ICH reflection papers propose future guideline work and harmonization efforts on a specific guideline begin after endorsement by the ICH assembly.
During a recent webinar hosted by the Alliance for a Stronger FDA, Theresa Mullin, associate director for strategic initiatives in the US Food and Drug Administration's Center for Drug Evaluation and Research, said that the agency worked with the European Medicines Agency to propose that ICH produce a reflection paper on PFDD.
The guideline work will “make sure that trials around the world can actually be using data collection tools, patient experience data collection, that's going to be fit for purpose and submitted to regulators, whether it's in the US, or Europe or Asia, South America, Africa, etc.,” Mullin said.
Path To Guidance
The FDA anticipates the proposed work will get underway in the next few years, but noted that achieving international harmonization usually is a multi-year process that involves in depth scientific discussions to reach consensus among experts.
Once a draft guideline is developed it will be made public on ICH’s website. Regulators in each ICH member region will then follow their own consultation process. The FDA will publish the guideline as draft guidance in the Federal Register with a request for public comment.
The ICH guideline working group then will review and discuss the comments from the public in the various regions and consider if further revisions are needed to reach a single harmonized guideline. Once the guideline is revised and finalized, it will be published on ICH’s website and then published as an FDA guidance.
Terminology, Methodology, Data Collection
The comments ICH received on the reflection paper indicate issues that will be addressed in developing the guideline. A summary report notes that several respondents requested that the guidance include a clear outline of what constitutes acceptable and/or desirable criteria for qualitative data and what level of “robustness criteria” is acceptable for regulators.
Many comments requested clarification of the terminology used, such as “patient centricity,” “patient experience data,” “PFDD,” and “patient preferences.”
Other comments noted the need to consider specific groups when collecting patient data and engage patients at the start of drug development when defining goals, as well as to involve them in development of all new standards and tools to assess quality of life during treatment.
Various comments addressed research methodology. For example, some stakeholders said the guideline should consider how to evaluate patient outcomes in progressive conditions, or with no historical data, and how to link to bio-clinical measures.
Several comments cited the need to include patient-reported outcomes generated in a real-world setting with guidance on tracking patient outcomes in this context, and suggested inclusion of field experience from pharmacists and those in primary care. Others cited the need for novel approaches to collecting data, such as from social media, websites, remote monitoring, e-consent and home visits.
“Comments frequently emphasized the need to align, harmonize or build upon existing tools and guidances, where appropriate, and not to ‘redo’ standardized methodologies that exist,” ICH stated.
Other Steps Toward Harmonization
In addition to working through ICH, the FDA also has worked on other projects with various regulators to harmonize patient input collection and use.
For example, the agency has participated in projects under the Innovative Medicines Initiative (IMI), a public-private partnership in the life sciences. One of the initiatives is the Patient Preferences in Benefit-Risk Assessments During the Drug Life Cycle (PREFER) project. PREFER is a public-private partnership between the European Federation of Pharmaceutical Industries and Associations and the European Commission.
Last year, the EMA issued a draft opinion for consultation on a proposed framework developed by PREFER that explains when and how companies can perform patient preference studies and incorporate their outcomes in regulatory and health technology assessment (HTA) decision-making throughout a product’s life cycle. The EMA endorsed the framework in May. (Also see "EU Project Findings To ‘Instil Confidence’ In Using Patient Preference Studies" - Pink Sheet, 16 Jun, 2022.)
The FDA has also worked on IMI’s Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials (SISAQOL) initiative, an international consortium co-led by the European Organization for Research and Treatment of Cancer and Boehringer Ingelheim GmbH. The four-year project began in January 2021 and will attempt to recommend standardized use, analysis and interpretation of patient reported outcome data in cancer clinical trials. The consortium includes 41 stakeholder groups from the pharmaceutical industry, academia, non-profit associations, cancer institutes, regulators and patient advocacy groups.
The FDA also collaborates with the EMA on patient engagement activities through the FDA/EMA Patient Engagement Cluster, which allows the two agencies to share best practices for involving patients in drug and biologic regulatory lifecycles. Created in 2016, it is one of several areas of cooperation through which they hold regular teleconferences.