FDA issues draft guidance regarding the implementation of Decentralized Clinical Trials to advance medical product development and research

 

On May 2, 2023, the U.S. Food and Drug Administration have released a new draft guidance that provides recommendations for sponsors, investigators and other stakeholders regarding the implementation of Decentralized Clinical Trials (DCTs) to advance medical product development and research.

Examples of decentralized elements include obtaining laboratory tests at a local facility rather than a research medical center or conducting a clinical follow-up visit in the trial participant’s home using telemedicine.

Decentralizing clinical trials will allow some or all trial-related activities to take place at trial participants’ homes or other convenient locations, instead of having them visit research sites. By reducing barriers to participation, FDA expect that DCTs will increase the breadth and diversity of participants in clinical trials and improve accessibility for those with rare diseases or mobility challenges. FDA anticipate that this approach will facilitate the development of drugs including in areas of medical need, resulting in more treatment options and improved patient outcomes.

This draft guidance builds on FDA’s recommendations issued in 2020, which provided clarity for investigators to facilitate trial decentralization in response to the COVID-19 public health emergency and associated disruptions such as quarantines, site closures and travel limitations.

While the FDA’s regulatory requirements for investigations of medical products are the same for DCTs and traditional site-based clinical trials, the new draft guidance covers recommendations on topics such as:  

• design considerations for a DCT;
• conduct of remote clinical trial visits and clinical trial-related activities in a DCT;
• use of digital health technologies to remotely acquire data in a DCT;
• roles and responsibilities of the sponsor and investigators in a DCT;
• obtaining informed consent (IC) and institutional review board oversight of the IC process in a DCT;
• determination of the appropriateness of investigational products for use in a DCT;
• packaging and shipping of investigational products in a DCT; and
• safety monitoring of trial participants in a DCT.

The FDA expects that clinical trials with decentralized elements will play an important role in addressing public health needs.

FDA Guidance Documents Update

The US FDA have released the following guidance documents recently.


1. Guidance for Sponsors, Investigators, and Institutional Review Boards: Questions and Answers on Informed Consent Elements,21 CFR § 50.25(c) (Small Entity Compliance Guide)

http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM291085.pdf

2. Guidance for IRBs,Clinical Investigators,and Sponsors: IRB Continuing Review After Clinical Investigation Approval

http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM294558.pdf

3. Guidance for Industry and FDA Staff: FDA Acceptance of Foreign Clinical Studies Not Conducted Under an IND, Frequently Asked Questions

http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM294729.pdf

4. Guidance for the Public, FDA Advisory Committee Members, and FDA Staff: Public Availability of Advisory Committee Members' Financial Interest Information and Waivers, Final Guidance

http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM295372.pdf

WHO updates guidance for joint prevention, diagnosis and treatment of TB and HIV

Global health impact reported that an estimated 910 000 lives were saved globally over six years by improving collaboration between TB and HIV services that protect people living with HIV from TB. 

In 2004, WHO proposed the initial guidance on collaboration between TB and HIV activities and there was a 12-fold increase in the number of HIV people screened for TB. The number of HIV people screened for TB in 2010 was over 2.3 million. On the other hand, number of TB people screened for HIV rose from approximately half a million in 2005 to 2.2 million in 2010, a five fold increase!

These success stories have triggered WHO to release an updated global policy for joint prevention, diagnosis and treatment of TB and HIV. 

Since HIV being a disease of the immune system, people with HIV are much more likely to be infected with a variety of other diseases like HCV and TB.

The new policy calls for routine HIV testing for TB patients, people with symptoms of TB, and their partners or family members; provision of co-trimoxazole, a cost-effective medicine to prevent against lung or other infections for all TB patients who are infected with HIV; starting all TB patients with HIV on antiretroviral therapy (ART) as soon as possible (and within the first 2 weeks of starting anti-TB treatment) regardless of immune system measurements; evidence based methods to prevent the acquisition of HIV for TB patients, their families and communities.

More than 100 countries are now testing more than half of their TB patients for HIV. Progress was especially noteworthy in Africa where the number of countries testing more than half their TB patients for HIV rose from five in 2005 to 31 in 2010.

Click here to read the entire 36 pages policy document 

The new WHO Policy for joint prevention, diagnosis and treatment of TB and HIV will be presented in detail on 5 March at the annual Conference on Retroviruses and Opportunistic Infections (CROI), in Seattle, Washington.

Source: WHO

FDA proposes draft guidelines intended to improve the representation of women in medical device clinical studies

Draft guidance aimed to address the historic underrepresentation of women in clinical studies was issued by the U.S. Food and Drug Administration today. Intended for medical device developers and manufacturers, the guidance outlines agency recommendations for designing and conducting device clinical studies that may enhance the enrollment of women in such studies, if appropriate.

“The FDA recommends that investigators and manufacturers strive to enroll representative proportions of both women and men in their device studies,” said Jeffrey Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health. “Our draft guidance outlines what we recommend for obtaining and improving the quality and consistency of sex-specific data on devices.”

Certain medical products may elicit different responses in women than in men. This may be due in part to basic differences in men and women, including genetics, hormones, body size, diet, and sociocultural issues. In addition, certain variables associated with women, such as size or certain illnesses, may be responsible for certain differences between men and women in the safety and effectiveness of medical devices.

 

A 2001 report by the U.S. Government Accountability Office (GAO) on FDA-reviewed drug studies found that while women represented 52 percent of study enrollees, 30 percent of study documents did not report outcomes by sex and nearly 40 percent did not report enrollment demographics. A 2009 study of cardiovascular device pre-market applications showed that pivotal studies that reported sex enrolled an average of 33.9 percent women.

The draft guidance addresses study and evaluation of sex differences, data analysis and reporting in both pre- and post-market device clinical studies. In addition, it covers issues regarding statistical analyses of sex differences and how to report sex-specific information in summaries and labeling for approved devices.

Devices intended for single-sex use, of course, would not be expected to address potential sex differences.

The FDA is seeking input on this draft guidance during a 90 day public comment period. The draft guidance can be found at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm283453.htm.

FDA Activities Update

PRODUCT SAFETY:
FDA Drug Safety Communication: Safety review of post-market reports of serious bleeding events with the anticoagulant Pradaxa (dabigatran etexilate mesylate) (Dec 7)
FDA is evaluating post-marketing reports of serious bleeding events in patients taking Pradaxa (dabigatran etexilate mesylate).
CooperVision Avaira Aquaform Sphere Soft Contact Lenses: Class 1 Recall - Unintended Residue on Lenses (Dec 7)
The unintended presence of a silicone oil residue on lenses from certain lots of Avaira Aquaform Sphere contact lenses. Symptoms may range from hazy, blurry vision, discomfort to eye injuries requiring medical treatment.
FDA announces changes to risk strategy requirements for 2 drugs to treat low platelet counts (Dec 6)
The approval of changes to the Risk Evaluation and Mitigation Strategies (REMS) for both Nplate (romiplostim) and Promacta (eltrombopag) was announced by FDA.

For more product safety information, please visit our MedWatch website at http://www.fda.gov/medwatch


PRODUCT APPROVALS:

FDA approves first insomnia drug for middle-of-the-night waking followed by difficulty returning to sleep (Nov 23)
FDA approved Intermezzo (zolpidem tartrate sublingual tablets) for use as needed to treat insomnia characterized by middle-of-the-night waking followed by difficulty returning to sleep.

For information on drug approvals, please visit Drugs@FDA


OPPORTUNITIES FOR COMMENT AND/OR RECENTLY PUBLISHED GUIDANCES:
Request for Nominations for Voting Members on Public Advisory Committee, Science Board to the Food and Drug AdministrationFDA is requesting nominations for voting members to serve on the Science Board to the FDA. FDA has special interest in ensuring that women, minority groups, and individuals with disabilities are adequately represented on advisory committees and, therefore, encourages nominations of qualified candidates from these groups. Nominations received on or before December 28, 2011, will be given first consideration for membership on the Science Board.
Draft Guidance for Industry and Food and Drug Administration Staff; the Content of Investigational Device Exemption and Premarket Approval Applications for Artificial Pancreas Device Systems; AvailabilityThis draft guidance document provides industry and the Agency staff with guidelines for developing premarket submissions for artificial pancreas device systems, in particular, the Control-to-Range (CTR) and Control-to-Target (CTT) device systems. Comments due by March 5, 2012.
Guidance for Industry on Medication Guide Distribution Requirements and Inclusion of Medication Guides in Risk Evaluation and Mitigation Strategies; Availability FDA is announcing the availability of a guidance for industry entitled ‘‘Medication Guides— Distribution Requirements and Inclusion in Risk Evaluation and Mitigation Strategies (REMS).’’
Comment Request; Approach to Addressing Drug ShortageFDA is opening a comment period in light of public interest in this topic and in order to gain additional insight about the causes and impact of drug shortages, and possible strategies for preventing or mitigating drug shortages. Comments due by December 23, 2011.

ANNOUNCEMENTS:
Statement from FDA Commissioner Margaret Hamburg, M.D. on Plan B One-Step (Dec 7)
FDA has been carefully evaluating for over a decade whether emergency contraceptives containing levonorgestrel, such as Plan B One-Step, are safe and effective for nonprescription use to reduce the chance of pregnancy after unprotected sexual intercourse.
FDA, FTC act to remove “homeopathic” HCG weight loss products from the market (Dec 6)
FDA and the Federal Trade Commission (FTC) today issued seven Warning Letters to companies marketing over-the counter HCG products that are labeled as “homeopathic” for weight loss.
- FDA hosted a media teleconference on December 6 to discuss the removal of HCG weight loss products from the market. A replay is available until January 6, 2012 by calling 888-567-0390.
FDA outlines flexible approaches for artificial pancreas system clinical trials, product approvals (Dec 1)
FDA issued draft guidance designed to help investigators and manufacturers as they develop and seek approval for artificial pancreas device systems to treat type 1 diabetes.
- FDA hosted a stakeholder teleconference on December 1 to discuss the draft guidance. A replay of the teleconference is available until January 1, 2012 by calling 800-568-6276; passcode 12111.
FDA approves first generic version of cholesterol-lowering drug Lipitor (Nov 30)
FDA approved the first generic version of the cholesterol-lowering drug Lipitor (atorvastatin calcium tablets).

UPCOMING MEETINGS:
Circulatory System Devices Panel of the Medical Devices Advisory Committee (Dec 7-8)
Joint Meeting of the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee Meeting (Dec 8)
Joint Meeting of the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee Meeting (Dec 9)
Psychopharmacologic Drugs Advisory Committee Meeting (Dec 12)
Medical Devices Dispute Resolution Panel of the Medical Devices Advisory Committee Meeting (Dec 14)--CANCELLED
Antiviral Drugs Advisory Committee Meeting (Dec 14-15)
Public Workshop - The Development and Evaluation of Human Cytomegalovirus Vaccines (Jan 10-11)
Gastroenterology and Urology Devices Panel of the Medical Devices Advisory Committee Meeting (Jan 11)
Tobacco Products Scientific Advisory Committee Meeting (Jan 18-20)
Reproductive Health Drugs Advisory Committee Meeting (Jan 20)
Neurological Devices Panel of the Medical Devices Advisory Committee Meeting (Feb 20)
Dermatologic and Ophthalmic Drugs Advisory Committee Meeting (Feb 27)
Public Workshop - Role of Naloxone in Opioid Overdose Fatality Prevention; Request for Comments (Apr 12)

Please visit FDA’s Advisory Committee page to obtain advisory committee meeting agendas, briefing materials, and meeting rosters prior to the meetings. You may also visit this page after meetings to obtain transcripts, presentations, and voting results. For additional information on other agency meetings please visit Meetings, Conferences, & Workshops.

RESOURCES:

Continuing Education
The Clinical Investigator's CME Program: Transforming a Clinician Into an Investigator: What Does It Take?Panel discussion moderated by Dr. Leonard Sacks, Acting Director, Office of Critical Path Programs at FDA. This CME/CE activity will help clarify the responsibilities of clinical investigators and address some of the challenges that investigators face today.

Articles

Please visit Articles of Interest to access articles produced by FDA and written for a health professional audience. These articles include FDA News for Health Professionals articles, as well as articles that were published in health professional journals.

Videos
LASIK video
LASIK is a surgical procedure intended to reduce a person's dependency on glasses or contact lenses.
MedWatch Safety Information Resources for Busy Physicians A video discussing Medwatch Safety Alerts