The FDA has been busy this month issuing guidances on data monitoring committees (DMC), charging for investigational drugs and assessing COVID-19-related symptoms in outpatient trials. The agency also extended the comment deadline on its guidance for master protocols to March 21.

Meanwhile, a trio of Democrat lawmakers have penned a letter to the FDA urging it to focus on releasing legally mandated draft guidance that will direct sponsors on the content and format of diversity action plans.

Modernization of Guidance on Using DMCs

A new draft guidance from the FDA addresses significant developments in the use of DMCs, including their growing use outside of therapeutic areas that involve high morbidity or death.

The 26-page revised draft guidance would replace a March 2006 final guidance on DMCs, bringing the agency’s thinking up to date with how the committees are being used today.

“For example, DMCs can provide the specialized expertise to evaluate emerging efficacy and safety data for trials in rare diseases (e.g., certain genetic disorders), for trials in vulnerable populations (e.g., neonates) and for oncologic therapies with highly specific targets and potential serious risks (e.g., biological products for genetic targets, immunotherapies),” the guidance reads.

“They are also being used in early-phase trials in serious diseases or conditions,” it continues. “With the growth of DMC oversight, a variety of approaches to DMC operations has been developed. In some cases, sponsors have engaged a single DMC to oversee a clinical development program encompassing multiple trials.”

In addition to the growing use of DMCs in many therapeutic areas, the guidance specifically addresses:

• Greater use of DMCs in smaller-size trials
• DMC charters growing longer and more detailed
• Greater use of DMCs to enable adaptive trials
• Greater utilization of DMCs for overseeing entire development programs
• The broadening of DMC functions
• Clinical trials growing increasingly more global and multiregional trials increasingly using DMCs

The guidance would help sponsors determine whether to use a DMC for a clinical trial in addition to offering insights on DMC composition, charters, responsibilities, operations, interim data and analyses, independence, and regulatory reporting requirements, among other elements.

Comments on the draft guidance are due by April 15.

Read the full guidance here.

Minor Update to Guidance on Charging for Investigational Drugs

The FDA has published final guidance on charging for investigational new drugs in clinical trials and the expanded access program, offering a minor update that addresses informed consent and offers further clarity on offering expanded access to intermediate-size groups of patients.

The 23-question Q&A guidance answers questions across four sections: general questions, charging in clinical trials, charging for expanded access and sponsor cost recovery calculations.

The guidance informs sponsors that they are required to alert trial participants and patients treated under expanded access if they will be charged for an investigational drug, either in the informed consent document or through a written summary when a short form is used.

In addition, intermediate-size patient population expanded access, a category of expanded access, has been defined to mean “access to an investigational drug for use by more than one patient but generally fewer patients than are treated under a typical treatment IND or protocol.” The FDA points sponsors to its 2022 draft guidance, Expanded Access to Investigational Drugs for Treatment Use: Questions and Answers, for more information on expanded access categories.

Read the full guidance here.

Updated Guidance on Evaluating Common Symptoms in Outpatient COVID-19 Trials

The FDA has issued a new final guidance on assessing COVID-19-related symptoms in drug and biologics trials for outpatient prevention/treatment of the infectious disease, overriding its prior recommendations from September 2020.

The 11-page guidance, which aims to help address hurdles, including “the identification of methods to assess the numerous and heterogenous symptoms across subjects, patient burden, poor compliance with diary completion and potential missing data,” consists of general recommendations, an example assessment of critical COVID-19-related symptoms, considerations for outpatient trial endpoints, advice on data-handling and a section on additional COVID assessments.

The FDA recommends dealing with these challenges by optimizing the evaluation methods for symptoms with the highest likelihood of changing while cutting down on participant burden. In doing this, “sponsors should identify key common symptoms for daily assessments based on the program specific context of use (e.g., target population, mechanism of action of the investigational product, underlying pathophysiology of COVID-19, symptomatology associated with the currently circulating variants),” the guidance reads.

The guidance advises sponsors of COVID-19 outpatient trials to use comprehensible, practical patient-reported outcomes (PRO) to assess COVID-19-related symptoms, discuss these tools with the relevant FDA review division and conduct PRO assessments at least every 24 hours at the same time each day, among other PRO-related recommendations.

Read the full final guidance here.

Democrat Lawmakers Press FDA on Guidance for Diversity Action Plans

The FDA has missed its Dec. 29, 2023, deadline for releasing a legally mandated draft guidance to direct sponsors on the content and format of diversity action plans, charge a trio of lawmakers in a recent letter to the agency.

The letter from Reps. Frank Pallone, Jr. (D-N.J.), Kathy Castor (D-Fla.) and Anna Eshoo (D-Calif.) requests an update as to the status of the draft guidance (CenterWatch Weekly, April 3, 2023).

“Without FDA first publishing the draft guidance, sponsors will have difficulty preparing to carry out these diversity action plans,” the lawmakers wrote. “This draft is also the first step that must occur before the agency can enforce [the] diversity action plan requirement, which only goes into effect 180 days after guidance is finalized. Thus, the failure to meet this critical deadline delays the implementation of important efforts to improve diversity in clinical trials.”

Read the letter here.