The Department of Health and Human Services and 15 other agencies have announced revisions to the Federal Policy for the Protection of Human Subjects, otherwise known as the Common Rule. The final rule can be found here and will be officially published in the Federal Register on January 19, 2017.
The changes to the rule that will have a significant impact on the conduct of pragmatic clinical trials and embedded research include:
New requirements regarding the information that must be given to patients as part of the informed consent process, including
Key information that is most important to the subject and likely to help a patient (or legal representative) make a decision about participation
An opportunity to discuss the information
An approach that emphasizes the fostering of overall understanding (as opposed to specific length requirements)
Allowing the use of broad consent for the use of identifiable information or identifiable biospecimens for other research studies (other than the proposed one) for
Storage and maintenance for secondary research use
Secondary research (including future uses)
New exempt categories of research based on risk profile
A requirement for U.S.-based institutions engaged in cooperative research to use a single Institution Review Board (IRB)
A removal of the requirement for continuing review of ongoing research for studies that undergo expedited review.
The FDA has released a Draft Guidance for Industry to facilitate the use of data from electronic health record (EHRs) in clinical investigations. The draft guidance provides recommendations on how to use EHRs as a source of data for research, ensure data quality and integrity, and satisfy the FDA’s inspection, recordkeeping, and record retention requirements. An additional goal of the draft guidance is to promote interoperability, or the ability to exchange and use information between EHR systems that capture information during patient care visits and electronic data capture (EDC) systems that support clinical investigations. Sponsors of clinical research must also consider whether there are any reasonably foreseeable risks involved in using the EHR for research—such as an increased risk of data breaches—that should be disclosed in the informed consent document.
As part of their ongoing effort to improve the speed and efficiency of conducting clinical trials, the NIH-FDA Joint Leadership Council has created a draft clinical trial protocol template. The template contains instructional and sample text intended to assist NIH-funded investigators in writing protocols for phase 2 or 3 clinical trials that require Investigational New Drug (IND) or Investigational Device Exemption (IDE) applications. Feedback is sought from investigators, investigator-sponsors, institutional review board members, and other stakeholders involved in protocol development and review.
Our goal is to provide an organized way for creative investigators to describe their plans so that others can understand them. – Dr. Pamela McInnes, NIH
Details on the rationale and development of the protocol template are on these blog posts:
A new report (PDF) containing recommendations for the creation of a national registry system for evaluating and monitoring medical devices has been released for public comment today. The report, a joint project of the Medical Device Registry Task Force and the Medical Device Epidemiology Network (MDEpiNet), is available on boh the US Food and Drug Administration (FDA) website and on the MDEpiNet website.
The report reflects the results of a year-long effort, prompted by the FDA’s Center for Devices and Radiological Health (CDER), that is focused on fostering a national system for monitoring the use of medical devices in the “real-world” setting of patient care, once the devices have been approved for the market (known as “postmarket surveillance”).
The term “medical devices” encompasses a wide range of technologies, including implantable pacemakers, cardiovascular stents, robotic surgical devices, and artificial joint replacements, among many others. At present, information about the use of these devices in routine care settings, including safety issues reported by doctors and patients, is collected in a variety of registries and health record systems. A networked national system, such as the one described in the task force report, would be able to unite and build upon both existing and novel data resources, thereby improving safety monitoring and accelerating the development of new devices:
“Task Force recommendations for [Coordinated Registry Network] CRN architecture, and thus for the National System, center on leveraging existing, self sustaining electronic resources, such as device registries, electronic health records, administrative data and even social media and personal mobile device sources.”
The Task Force Report offers recommendation in several key areas, including:
Establishing a national dialog about medical device evaluation that includes all stakeholders;
Leveraging existing efforts in the arena of device registries and electronic data systems;
Describing the desired characteristics of a national Coordinated Registry Network (CRN) for medical devices;
Outlining priorities for developing and refining medical devices in multiple therapeutic areas;
Identifying and improving methods for analyzing data on medical devices; and
Addressing network governance and issues related to patient privacy and informed consent.
Each of these key areas also features suggested pilot projects designed to inform ongoing efforts.
A related perspective article summarizing the National Registry System project has also been published online in the Journal of the American Medical Association.
A new analysis of data from the ClinicalTrials.gov website shows that despite federal laws requiring the public reporting of results from clinical trials, most research sponsors fail to do so in a timely fashion—or, in many cases, at all. The study, published in the March 12, 2015 issue of the New England Journal of Medicine, was conducted by researchers at Duke University and supported by the NIH Collaboratory and the Clinical Trials Transformation Initiative (CTTI). The study’s authors examined trial results as reported to ClinicalTrials.gov and evaluated the degree to which research sponsors were complying with a federal law that requires public reporting of findings from clinical trials of medical products regulated by the U.S. Food and Drug Administration (FDA).
“We thought it would be a great idea to see how compliant investigators are with results reporting, as mandated by law,” said lead author Dr. Monique Anderson, a cardiologist and assistant professor of medicine at Duke University.
Using a publicly available database developed and maintained at Duke by CTTI, the authors were able to home in on trials registered with ClinicalTrials.gov that were highly likely to have been conducted within a 5-year study window and to be subject to the Food and Drug Administration Amendments Act (FDAAA). This federal law, which was enacted in 2007, includes provisions that obligate sponsors of non-phase 1 clinical trials testing medical products to report study results to ClinicalTrials.gov within 12 months of the trial’s end. It also describes allowable exceptions for failing to meet that timeline.
However, when the authors analyzed the data, they found that relatively few studies overall—just 13 percent—had reported results within the 12-month period prescribed by FDAAA, and less than 40 percent had reported results at any time between the enactment of FDAAA and the 5-year benchmark.
“We were really surprised at how untimely the reporting was—and that more than 66 percent hadn’t reported at all over the 5 years [of the study interval],” said Dr. Anderson, noting that although prior studies have explored the issue of results reporting, they have until now been confined to examinations of reporting rates at 1 year.
Another unexpected result was the finding that industry-sponsored studies were significantly more likely to have reported timely results than were trials sponsored by the National Institutes of Health (NIH) or by other academic or government funding sources. The authors noted that despite a seemingly widespread lack of compliance with both legal and ethical imperatives for reporting trial results, there has so far been no penalty for failing to meet reporting obligations, even though FDAAA spells out punishments that include fines of up to $10,000 per day and, in the case of NIH-sponsored trials, loss of future funding.
“Academia needs to be educated on FDAAA, because enforcement will happen at some point. There’s maybe a sense that ‘this law is for industry,’ but it applies to everyone,” said Anderson, who points out that this study is being published just as the U.S. Department of Health and Human Services and the NIH are in the process of crafting new rules that deal specifically with ensuring compliance with federal reporting laws.
According to Anderson, increased awareness of the law, coupled with stepped-up enforcement and infrastructure designed to inform researchers about their reporting obligations, have the potential to improve compliance with both the letter and the spirit of the regulations. “I think reporting rates will skyrocket after the rulemaking,” she says.
In the end, Anderson notes, reporting clinical trials results in order to contribute to scientific and medical knowledge is as much an ethical obligation for researchers as a legal one: “It’s something we really promise to every patient when they enroll on a trial.”
On March 9, 2015, the U.S. Food and Drug Administration (FDA) issued draft guidance on the Use of Electronic Informed Consent in Clinical Investigations (document opens as a PDF). In a question-and-answer format, the guidance provides recommendations for 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, and medical devices, and combinations thereof.
Electronic informed consent, or eIC, refers to the use of electronic systems and processes to convey information related to the study and to obtain and document informed consent. Electronic media formats may include text, graphics, audio, video, podcasts, and interactive websites, biological recognition devices, and card readers. Use of electronic systems may allow for rapid notification to study participants of any amendments pertaining to the informed consent, promote timely entry of eIC data into the study database, and allow for timely collection of the informed consent data from remote locations.
The guidance provides answers to these questions:
How should the information in the eIC be presented to the subject?
How and where may the eIC process be conducted?
How and when should questions from subjects be answered?
What steps may be taken to facilitate the subject’s understanding of the information being presented?
What steps may be taken to ensure that new or additional information is conveyed to the subject during the course of the clinical investigation?
Does FDA allow the use of electronic signatures to document eIC?
What special considerations should be given to the use of eIC for pediatric studies?
Should subjects receive a copy of their eIC and have easy access to the material and information presented to them in their eIC?
What steps can be taken to help ensure confidentiality of the information once eIC is obtained?
Can HIPAA authorizations for research, which are frequently combined with informed consent documents, be obtained electronically?
What are the IRB’s responsibilities in the eIC process?
What eIC documentation does FDA require for submission with applications?
What steps can be taken to ensure the system archives the documents appropriately?
What materials or documents will FDA require during an inspection?
The comment period ends May 7, 2015. Users can submit electronic comments using the docket number HHS-OPHS-2015-0002 at the Federal eRulemaking Portal: http://www.regulations.gov.
Guidance documents represent the FDA’s current thinking on particular topics and are used by stakeholders to understand the agency’s interpretation of regulations and policies.
There are approximately 3,000 guidance documents available on the site, which can be searched by keyword or filtered by date issued, FDA organizational unit, subject, draft or final status, and comment period.
The search feature was implemented in January 2015 in response to site visitor feedback.
On November 19, 2014, the U.S. Department of Health and Human Services issued a Notice of Proposed Rulemaking (NPRM), which proposes regulations to implement reporting requirements for clinical trials that are subject to Title VIII of the Food and Drug Administration Amendments Act of 2007 (FDAAA). According to FDA Commissioner Margaret A. Hamburg, MD:
This proposed rule would close an important gap, making additional information about clinical studies of investigational drugs, medical devices, and biological products available to the public. It would help eliminate unnecessary duplicative trials, advance biomedical innovation, and provide the public with a much richer understanding about the clinical trials for these products.
A streamlined approach for determining which trials are subject to the proposed regulations and who is responsible for submitting required information.
Expansion of the set of trials subject to summary results reporting to include trials of unapproved products.
Additional data elements that must be provided at the time of registration (not later than 21 days after enrolling the first participant) and results submission (generally not later than 12 months after completion).
Clarified procedures for delaying results submission when studying an unapproved, unlicensed, or uncleared product or a new use of a previously approved, licensed, or cleared product and for requesting extensions to the results submission deadline for good cause.
More rapid updating of several data elements to help ensure that users of ClinicalTrials.govhave access to accurate, up-to-date information about important aspects of a clinical trial.
Procedures for timely corrections to any errors discovered by the responsible party or by the Agency as it processes submissions prior to posting.
In August 2014, the Food and Drug Administration (FDA) released an action plan(link opens as a PDF) aimed at encouraging more diverse patient participation in drug and medical device clinical trials. The Action Plan to Enhance the Collection and Availability of Demographic Subgroup Data includes 27 responsive and pragmatic actions, divided into 3 overarching priorities:
Data quality: improving the completeness and quality of demographic subgroup data collection, reporting, and analysis
Participation: identifying barriers to subgroup enrollment in clinical trials and employing strategies to encourage greater participation
Transparency: making demographic subgroup data more available and transparent
The plan follows an August 2013 report to Congress on these concerns and reflects the agency’s commitment to encouraging the inclusion of a diverse patient population (with reference to sex, age, race, and ethnicity) in biomedical research that supports applications for FDA-regulated medical products. Increasing representation is a multifaceted challenge that requires a multifaceted approach and collaboration of federal partners, industry, healthcare providers, patients and patient advocacy groups, academicians, and community groups.
A messagefrom the Commissioner of the FDA contains background and details.
The guest speaker for this Friday’s Collaboratory/PCORnet Grand Rounds presentation will be the FDA’s Janet Woodcock, MD. Dr. Woodcock is the current director of the Center for Drug Evaluation and Research (CDER), the division of the FDA primarily responsible for evaluating the safety and effectiveness of both prescription and over-the-counter drugs and biologic therapies marketed in the United States.
The Grand Rounds presentation will take place from 1:00-2:00 PM Eastern time on Friday, March 26. Details are available here. Archived video and slide sets from the presentation will be available early the following week; links to archived material will be provided in an update to this post.