The FDA has issued more than 30 guidance documents related to drug development so far this year. BioSpace takes a closer look at six of them.
Pictured: FDA headquarters/iStock, Grandbrothers
The FDA has issued a flurry of draft and final guidance documents this year pertaining to drug development, including ones aimed at increasing available data on diverse patient populations, facilitating the approval of more medicines for kids and addressing risks associated with laboratory developed tests for cancer drugs.
BioSpace takes a closer look at six of the more than 30 documents that could have a significant impact on the drug development space.
New Guidance on One Study Plus Confirmatory Evidence for Approval
In a possible nod toward greater regulatory flexibility, the FDA on Monday issued a new draft guidance outlining how “one adequate and well-controlled” clinical trial may be used to meet the regulator’s substantial evidence bar. While stressing that its standard for demonstrating evidence hasn’t changed since guidance was issued in 1998, the FDA allows that science and drug and biologic development has evolved, resulting in changes in the types of development programs it receives.
The FDA advises drug sponsors to consider the clinical context, disease or condition and data required to demonstrate safety, when determining whether to base their development plans on one study plus confirmatory evidence. The draft guidance document—which builds on those previously issued in 1998 and 2019—encourages early communication with the FDA, including a pre-IND meeting before the end of Phase II. It also outlines the types of confirmatory evidence that can be used to substantiate one well-controlled trial. These include clinical evidence from a closely related indication, strong mechanistic evidence of a drug’s efficacy in a particular disease, natural history evidence and real-world data.
Original article published 9/15
Informed Consent Guidance for IRBs, Clinical Investigators, and Sponsors
Issued in August, this document clarifies requirements for informed consent for clinical trial participants. It offers guidance on funding disclosures, statements involving unforeseen risks, situations where an investigator must end a subject’s participation without their informed consent and consequences when a participant chooses to withdraw from a study.
It also reaffirms general requirements, including that study information must be provided to the participant—or their authorized representative—in a language they can understand, and that the information must not be written in a way that would require the participant to waive any legal rights. The updated guidance finalizes the initial Informed Consent Information Sheet, which was issued in July 2014.
Post-marketing Approaches to Obtain Data on Underrepresented Populations
Also in August, the FDA released guidance aimed at supporting diversity in drug development. The document—which is focused on gleaning data on populations that are historically underrepresented in clinical research—discusses design and statistical considerations for subpopulation analyses, post-marketing approaches to obtaining information on a drug’s benefit-risk profile and mechanisms by which the FDA can request safety and efficacy data be collected in this setting.
The FDA notes in the document that disease prevalence and outcomes can vary based on race, ethnicity, sex and age, among other demographic factors, and that having safety and efficacy data on a drug across diverse populations “is important to support the generalizability of the results” to the broad population expected to take it.
The new guidance follows other documents with similar aims, including the Collection of Race and Ethnicity Data in Clinical Trials guidance, issued in October 2016, and the Enhancing the Diversity of Clinical Trial Populations –Eligibility Criteria, Enrollment Practices, and Trial Designs guidance, published in November 2020.
Guardrails Around Certain Laboratory-Developed Tests
Precision cancer therapeutics are often approved alongside a companion diagnostic test (CDx) that analyzes human samples for biomarkers to help match patients to specific treatments. But in some cases, a precision therapy that requires such a test will be approved before a CDx is authorized. In such circumstances, healthcare providers may use a laboratory developed test (LDT) to aid in treatment decisions. Developed and used within a single lab, such tests have generally been exempt from premarket review by the FDA.
But in June, the FDA stated in a press release that it has become “increasingly concerned” that these tests might not provide accurate, reliable results, and introduced a voluntary pilot program intended to address these risks. Using performance information for tests used to enroll patients in clinical trials for subsequently approved drugs, the FDA will publish minimum performance characteristics for LDTs that don’t require approval by the agency. Labs developing LDTs will then be able to refer to these guidelines when developing future tests.
Recommendations on Decentralized Clinical Trials
Decentralized clinical trials (DCTs)—those occurring either partly or completely outside of traditional clinical trial sites—ballooned in popularity during the COVID-19 pandemic, and the Food and Drug Omnibus Reform Act requires the FDA to issue or revise draft guidance with recommendations to “clarify and advance” the use of DCTs before the end of 2023. So, in May, the regulator issued draft guidance with recommendations for the implementation of these trials.
In a press release issued at the time, the FDA said the guidance is meant to support DCTs, with the ultimate goal of diversifying clinical trial participation and improving trial recruitment and retention.
In a previous interview with BioSpace, Jeffrey Zucker, senior vice president of decentralized clinical trial solutions and optimization at Worldwide Clinical Trials, called the draft guidance “a real game changer” and said he expects it will increase the number of DCTs.
The recommendations include guidance around the use of videoconferencing and other technologies, the delegation of certain trial-related activities to healthcare providers and the number of participants that can be enrolled in DCTs. This guidance builds on recommendations issued in March 2020.
Pediatric Drug Development Guidance
In May, the FDA issued two new guidance documents intended to improve the pediatric drug development landscape. Over the past 20 years, the regulator has been increasingly focused on a push to bring more drugs, biologics and vaccines for children to the U.S. market, spurred by legislation including the Best Pharmaceuticals for Children Act (BPCA) of 2002 and the Pediatric Research Equity Act (PREA), passed a year later. The two new guidance documents are meant to build on these laws.
Among other issues, the guidances address certain clinical, scientific and ethical considerations, the inclusion of children in adult clinical trials, and recommendations that drug companies submit their initial pediatric study plans (IPSPs) “earlier than is required,” especially if the patient population for their drug’s indication is made up primarily of children.
Currently, the FDA says, most drugs have not been tested in children, resulting in many physicians prescribing these drugs “off-label” for kids.
Heather McKenzie is a senior editor at BioSpace. You can reach her at heather.mckenzie@biospace.com. Follow her on LinkedIn and X @chicat08.
