Mwango Kashoki, MD, MPH, Vice President, Technical, Parexel International, USA*
Interviewed by Sally Hassan, PhD, ISMPP CMPP™, Parexel International, UK.
* The opinions expressed within are the author’s own and do not necessarily reflect the views of the author’s employer.

“What I Would Like You to Know” is an article series that shares perspectives and insights from functional area colleagues that collaborate with medical publication professionals on the planning and development of scientific publications. This article series will appear periodically in The MAP.

This article spotlights a regulatory expert’s perspective, presented in a question-and-answer format.

What are one or two things you want your medical publication colleagues to know from your experience as a regulatory professional working on scientific publications?

Increasingly, authors of medical publications aim to provide regulatory context for, or demonstrate the regulatory significance of, their findings with respect to unmet medical needs, improved treatment methodologies, superiority of a therapy compared with available therapies, or consistency with a drug’s approved labeling. Appropriately describing the regulatory context within which scientific studies are interpreted and used for decision-making by health authorities is complex. Furthermore, during publication development, it is challenging to distill down those complexities into brief sentences or paragraphs, and oversimplification of the regulatory context can occur. Additionally, some authors lack the regulatory insight of those who work in regulatory health agencies or colleagues within their organizations who may have this insight, resulting in regulatory concepts being confused or misinterpreted.

For example, there are many publications on studies of drugs that are conducted by pharmaceutical companies after approval, which are referred to, in the United States (US), as post-marketing commitments (PMCs) or post-marketing requirements (PMRs). The status and results from these post-approval studies, and the actions that the US Food and Drug Administration (FDA) takes to address delayed studies or adverse findings, are of keen interest to the health community. However, authors frequently confuse PMRs and PMCs, misinterpret their statuses, or misunderstand the actions of the FDA against delayed studies.

  • A PMR is a study that is required by the FDA. The authorities under which PMRs are issued are different, as are the associated actions the FDA can take against companies that are noncompliant with requirements. For example, the Pediatric Research and Equity Act (PREA) authorities allow the FDA to require a company to conduct post-approval drug studies in pediatric patients. Also, the FDA Amendments Act (FDAAA) authorizes the FDA to require a post-approval study to further evaluate a safety issue associated with a drug. Whereas noncompliance with PREA requirements can ultimately lead to the drug being considered misbranded, to an injunction seizure proceedings, or both, against the company, failure to comply with an FDAAA study requirement can result in, among other actions, the imposition of civil monetary penalties (fines) by the FDA against a drug company.
  • In contrast to PMRs, PMCs are studies that the FDA requests and pharmaceutical companies agree to conduct. Although the FDA can negotiate with a company to fulfill a PMC, the FDA lacks the regulatory authority to require the company to perform it. The FDA monitors the status of PMRs and PMCs, noting which ones are on track according to key milestones and the reasons for any delays in conducting a study, allowing for revision of milestones, as appropriate. The FDA determines when to take action against noncompliance with PMRs, depending on the reason for delay.

When describing fines from PMRs and PMCs, some publications have incorrectly grouped PMRs and PMCs, termed certain studies as delayed, or criticized the FDA for failing to impose fines for all delayed PMRs.

Another regulatory area of interest to authors is expedited development of drugs. Across multiple regions, drug regulatory agencies have established various programs aimed at accelerating development and approval of drugs intended to treat serious diseases for which there is an unmet medical need. Authors frequently attempt to assess the scope and effects of such programs, and to what extent they positively impact patient outcomes. This regulatory area can be complicated because the purposes, qualifying criteria, and characteristics of expedited development programs are different from standard drug review processes, and it is essential to consider these differences when making conclusions about the impact of these expedited programs.

Additionally, because there is an overlap of terms and programs across regulatory regions, authors must be careful not to confuse these when comparing expedited development across different countries. For example, “accelerated assessment” in the European Union (EU) refers to a reduced timeframe for the European Medicines Agency (EMA) to review a marketing application and is similar to the FDA’s “priority review” program. “Accelerated assessment” in the EU is distinct from the “accelerated approval” pathway in the US, which is an authority that allows the FDA to approve drugs for a serious condition that fulfills an unmet medical need based on a surrogate endpoint.

What is one improvement you would suggest for the development of scientific publications that include regulatory information?

It is helpful and important to explain why presented data are relevant in the context of a regulatory challenge and/or its implications. One recommendation is to seek input and/or peer review from former regulators who are knowledgeable about the topic, at the outset, before publication development begins, but especially before submitting the paper to a journal. Former regulators can help ensure correct interpretation of regulatory laws and policies and can give additional insights into how findings further inform the regulatory context. Researchers and writers often read laws, guidelines, and regulations, but understanding them is like the art of medicine (i.e., although it can be studied, understanding regulatory nuances requires practice and experience).

What is your biggest challenge when contributing to the development of scientific publications that include regulatory information?

Because scientific publications have word limits, it is challenging to discuss regulatory issues and context concisely and factually while including all relevant information. A further challenge can be presenting findings and regulatory context that are up to date in terms of data or the current regulatory environment. Outside of a regulatory agency, access to the latest information (e.g., certain drug statistics or non-published changes to regulatory policies) can be a limitation.

What key recommendations from a regulatory perspective would you give to colleagues working on scientific publications?

Publications that assess regulatory information in a new way are helpful to regulatory agencies, such as the FDA, because they offer additional perspectives and further encourage thinking beyond precedent and can also suggest solutions for future implementation. The regulatory context of a study and description of the regulatory relevance of findings must be accurately conveyed to strengthen the publication’s value. To obtain the most up-to-date data, researchers and authors can request data or policy information directly from the regulatory agency, such as through the Division of Drug Information at the FDA. Authors who are unfamiliar with drug regulations and policies can access education and training resources provided by regulatory agencies. For example, the FDA’s Small Business & Industry Assistance (SBIA) website offers multiple learning resources that assist both individual researchers and small pharmaceutical companies in understanding the core aspects of drug development. Finally, I emphasize my recommendation to obtain input from a regulatory expert when conceptualizing a study and discussing its findings.

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