FDA Releases Draft Guidance on Acceptance of Medical Device Clinical Data from Studies Conducted Abroad

This post was written by Vicki Morris and Jennifer Pike.

On April 21, 2015, the Food and Drug Administration (FDA) issued a notice announcing the availability of a draft guidance document clarifying the Agency’s acceptance of medical device clinical data from studies conducted outside of the United States (“OUS”). The guidance arises from the 2012 Food and Drug Administration Safety and Innovation Act § 1123, amending Food, Drug & Cosmetic Act § 569B, which codified FDA’s longstanding practice of accepting scientifically-valid clinical data obtained from foreign clinical studies in support of premarket submissions for devices. Thus, the guidance is not intended as a new policy announcement, but rather as a description of FDA’s existing approach to this topic.

The draft guidance highlights special considerations that apply when using foreign clinical data, including applicability to populations within the US, and provides recommendations to assist sponsors in ensuring their data are adequate under applicable FDA standards. Specifically, FDA focuses on considerations sponsors of device submissions should take into account when initiating, or relying on previously collected data from a foreign clinical study to support an Investigation Device Exemption (IDE), Premarket Notification (510k), De Novo Petition, Humanitarian Device Exemption (HDE), or Premarket Approval Application (PMA). To illustrate these considerations, FDA includes in the draft guidance several hypothetical examples depicting when data will be acceptable.

As noted in the draft guidance, the number of IDE applications and submissions for marketing authorization supported by OUS clinical trials has increased in recent years and will likely continue to increase in the future. This increasing globalization of clinical trials presents challenges to both US and foreign regulators. Among the challenges are resource constraints that impact the number of foreign clinical site inspections and unnecessary duplication of clinical studies and administrative burdens. As such, in publishing the draft guidance, FDA believes that promoting greater clarity concerning the Agency’s use of foreign study data will minimize the possibility for additional or duplicative U.S. studies, further efforts to harmonize global clinical trial standards, and promote public health and innovation.

Comments on the draft guidance are due to FDA by July 20, 2015 and can be submitted here.

FDA Hosting Workshop on April 1 to Discuss Clinical Outcome Assessments

As mentioned on our Health Industry Washington Watch blog, the FDA will host a public workshop on April 1, 2015 to provide updates on the use of clinical outcome assessments (COAs), as well as to address plans for future development and use of COAs in drug development programs. The workshop, entitled “Clinical Outcomes Assessment Development and Implementation: Opportunities and Challenges,” will also cover the inclusion of patient-centered outcome measures, COA usage standards and collaborative processes for the development and dissemination of COAs. Participants may attend in person or via webcast. If you are interested in attending, please register no later than March 27, 2015.

FDA Draft Guidance Addresses Electronic Informed Consent in Clinical Investigations

This post was written by Deb McCurdy.

Today the Food and Drug Administration (FDA) published a notice announcing the availability of a draft guidance document entitled “Use of Electronic Informed Consent in Clinical Investigations: Questions and Answers.” The draft guidance provides recommendations for clinical investigators, sponsors, and institutional review boards (IRBs) on the use of electronic media and processes to obtain informed consent for FDA-regulated clinical investigations of medical products, including human drug and biological products, medical devices, and combinations thereof. The guidance provides recommendations on procedures that may be followed when using an electronic informed consent (eIC) to help:

  1. ensure protection of the rights, safety, and welfare of human subjects
  2. ensure the subject's comprehension of the information presented during the eIC process
  3. ensure that appropriate documentation of consent is obtained when electronic media and processes are used to obtain informed consent
  4. ensure the quality and integrity of eIC data included in FDA application submissions or made available to FDA during inspections

FDA is requesting comments on the draft guidance; to be assured of consideration during development of the final version, submit comments by May 8, 2015. Note that while the document is issued by FDA and is drafted as guidance that would apply to FDA-regulated clinical investigations, the HHS Office for Human Research Protections (OHRP) is considering whether to adopt the positions and recommendations proposed in this guidance for research regulated under the HHS protection of human subjects regulations, 45 CFR part 46, and to issue a joint OHRP and FDA guidance document on this topic when the final guidance document is developed.

Public Consultation Examines Potential Confidentiality Issues with New European Clinical Trial Regulations

Since January 21, the European Medicines Agency (EMA) has been holding a public consultation on the new European Clinical Trial Regulations (CTRs), which are intended to streamline the application process for clinical trials and increase the availability of information and results. However, the CTRs have met with some concerns regarding commercial and patient confidentiality. As described by Reed Smith attorneys John Wilkinson, Nicola Maguire and Adam Lewington in “European Clinical Trial Regulations Public Consultation – Confidentiality Concerns,” the new CTRs propose two exceptions for the disclosure and publishing of clinical trial information on the EMA’s publically accessible portal and database. These exceptions would allow clinical trial sponsors to withhold information that could compromise economic interests or be classified as identifiable personal data. The public consultation concludes today (February 18), with results of the consultation being published thereafter.

To read the client alert, click here.

False Advertising Claims & The First Amendment

Over on Reed Smith’s AdLaw by Request blog, attorney Caroline Klocko discusses the U.S. Court of Appeals for the District of Columbia Circuit’s January 30th ruling that the Federal Trade Commission (FTC) can prohibit POM Wonderful LLC from advertising that its products are effective in combating illnesses and conditions such as heart disease, prostate cancer and erectile dysfunction. In making the decision, the appeals court rejected POM Wonderful’s stance that under the First Amendment, the company’s advertisements and claims are protected. The court also ruled that the support of one clinical trial is necessary before POM Wonderful can make any subsequent claims of disease-fighting effectiveness – a number that deviates from both the initial amount imposed on POM Wonderful by the FTC (two) and the amount requested by POM Wonderful in its appeal (zero).

To read the full post, click here.

U.S. Congressional Committees Address Drug And Device Approval

As mentioned on our Health Industry Washington Watch blog, committees in both the House of Representatives and Senate last week addressed the speed at which medical innovations are approved and available for patient use. The House Energy and Commerce Committee’s “21st Century Cures Act” discussion draft, released on January 27, 2015, is a wide-reaching bill that includes provisions regarding drug and device approval, clinical trials, Medicare coverage, and drug safety, among others. The Senate Health, Education, Labor and Pensions Committee’s “Innovation for Healthier Americans: Identifying Opportunities for Meaningful Reform to Our Nation’s Medical Product Discovery and Development” report, released on January 29, 2015, poses questions about effective targeting of government resources, the Food and Drug Administration approval process, clinical trial requirements, public-private partnerships, biomedical research, and U.S. regulations vs. international regulations.

Feedback is being accepted on both the House draft bill and the Senate report. There is no specified deadline for comments on the House draft; comments on the Senate report are due by February 23, 2015.

To read Debra McCurdy’s entire post, click here.

Proposed Rule Re Submitting Clinical Trial Registration and Results, Including Adverse Event Information, To ClinicalTrials.gov Database

As mentioned on our Health Industry Washington Watch blog, the National Institutes of Health has released a proposed rule designed to provide clarity on the requirements surrounding the submission of information to ClinicalTrials.gov, as mandated by the Food and Drug Administration Amendments Act of 2007.

Among the proposed requirements is summary results submission for clinical trials involving all pharmaceuticals, medical devices and biological products, regardless of whether they have been approved, licensed or cleared by the Food and Drug Administration, timetable restrictions for the registration of a clinical trial and submission of summary results, and guidelines for the reporting of adverse events.

The proposed rule will officially be published on November 21, 2014, and comments will be accepted for 90 days thereafter.

To read the entire post, click here.

FDA Draft Guidance Encourages Companies to Study Drugs for Treatment of CFS and ME and Provides Roadmap to Approval for this Indication

This post was written by Lindsey R. Harteis.

Citing the fact that there is no FDA-approved treatment for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), the FDA recently released draft guidance to expedite the development and review of drugs to address this “unmet medical need.” The guidance will not become finalized until after its notice/comment period ends on May 12, 2014. Though non-binding, it provides a roadmap for drug manufacturers to craft and conduct studies that are more likely to succeed in satisfying the FDA clearance requirements that there be “substantial evidence” of the efficacy of the product and an acceptable risk/benefit profile.

The guidance addresses the following: selection and evaluation of efficacy endpoints; preferential domains to study; suggested methods for assessing each of these domains (if known); how to account for concomitant treatment and management of CFS/ME symptoms in study participants; safety considerations; recommendations for study protocol and design; and advice for testing combination drug products. The FDA expresses a clear interest in studying the following efficacy domains: symptoms; exercise capacity and post-exertional malaise; and health-related quality of life. It also suggests that “support from two definitive trials should [be sufficient to] establish efficacy for a drug product being developed to provide symptom relief for CFS/ME.” (There is no requirement that the two studies be identical.) Finally, studies should generally be placebo-controlled, double-blinded, randomized and parallel group studies. Of note, the guidance suggests that at least until there is one FDA-approved treatment for CFS/ME, study sponsors will be permitted to use placebo groups in trials.

The guidance also recommends sponsors discuss some specific aspects of study design and protocol with the FDA early in the process of developing the drug or studies about an existing drug.

New HHS Federal Research Conflict of Interests Regulations

On September 26, 2011, the U.S. Department of Health and Human Services ("HHS") issued new regulations governing the disclosure by faculty members and research staff of significant financial interests related to certain federal grants, and the reporting of "financial conflicts of interest" to certain federal agencies by colleges and universities that receive funding for Public Health Service ("PHS")-sponsored research. See 42 C.F.R. § 50.601 et seq.

The new regulations significantly expand the coverage of 1995 HHS regulations on the same subject. Colleges and universities that receive research funding from a PHS "Awarding Component," including the National Institutes of Health ("NIH"), must be in compliance with the new regulations by no later than August 24, 2012.

To learn more, read the full alert written by Lane Kneedler and Pakapon Phinyowattanachip available on Reed Smith's Global Regulatory Enforcement Law Blog.

The Legal Duties of Clinical Trial Sponsors

In an article entitled, "The Legal Duties Of Clinical Trial Sponsors," published by Law360.com on July 11, 2011, Reed Smith attorney Kevin Lohman addresses the risks involved in human clinical trials and the responsibilities between the clinical study investigator and the manufacturer/sponsor.  Although the unique roles and responsibilities of entities involved with clinical trials are clearly defined, plaintiffs oftentimes attempt to assign legal duties to the wrong entity — sometimes suing the clinical trial sponsor as if it were directly providing medical services to the participant — or attempt to create novel legal duties. Case law that has addressed this issue has consistently held that this is not appropriate. When faced with this scenario, it is important to clearly identify the role that the manufacturer/sponsor played in the clinical trial to determine whether they owed any legal duty to the plaintiff.

To read this article, you may download a .PDF or view on Law360.com (subscription required).

Increasing Clinical Trial Enrollment; Comments Requested

On January 13, 2009, the FDA published a notice seeking comments on issues related to the enrollment of certain populations in clinical drug trials. This request is related to FDA's implementation of the Food and Drug Administration Amendments Act of 2007 (FDAAA) section 901, which requires the FDA to report to Congress on best practice approaches to increasing participation of elderly populations, children, racially and ethnically diverse communities, and medically-underserved populations in clinical drug trials. FDA requests comments from medical product manufacturers, IRBs, patient groups, researchers, and other interested parties on possible approaches to increasing participation of these groups in clinical drug trials. Comments will be accepted until February 27, 2009.

Certifications of Clinical Trial Registry/Results Submissions; Final Guidance

The FDA has released final guidance on “Certifications To Accompany Drug, Biological Product, and Device Applications/Submissions: Compliance with Section 402(j) of The Public Health Service Act, Added By Title VIII of The Food and Drug Administration Amendments Act of 2007.” The guidance describes the FDA’s current thinking regarding the types of applications and submissions that sponsors, industry, researchers, and investigators submit to FDA and accompanying certifications under the FDAAA related to the submission of required information to the clinical trials data bank, www.ClinicalTrials.gov.

Under Construction: The Medicare Clinical Trial Policy

A lesser-known provision in the Medicare Program allows payment for "reasonable and necessary" items or services provided through clinical trials. At the same time, even for traditional reimbursement, the Centers for Medicare & Medicaid Services (CMS) increasingly is demanding evidence of effectiveness in the Medicare population, rather than simply in the general population, to support a coverage decision. The federal government has sought, often without much success, to increase participation by Medicare recipients in clinical trials, because Medicare recipients traditionally have been underrepresented in research populations--meaning the very evidence CMS seeks for traditional reimbursement often does not exist. Developments regarding these reimbursement policies by CMS are the subject of an informative and timely article for the FDLI UPDATE by Reed Smith attorney Kathleen McGuan.