The National Institutes of Health’s Office of Disease Prevention (ODP) has just released a free, self-paced online course on designing and analyzing pragmatic and group-randomized trials. The course, which is presented by ODP Director Dr. David Murray, includes a series of seven video presentations plus slide sets, reference materials, and guided activities.
Course segments typically last 25 to 35 minutes. Presentations can be accessed individually and include the following topics:
A new funding opportunity announcement from the NIH solicits applications to support Demonstration Projects that include an efficient, large-scale pragmatic clinical trial. Trials must be conducted across two or more health care systems (HCS) and must be conducted as part of the NIH HCS Research Collaboratory supported through the NIH Common Fund. Awards made through this FOA will initially support a one-year milestone-driven planning phase (UG3), with possible rapid transition to the second implementation phase (UH3) for a pragmatic trial Demonstration Project.
The NIH has issued a final policy requiring the use of a single institutional review board (sIRB) for multi-site non-exempt human subjects research funded by the NIH. The policy will take effect May 25, 2017.
According to the policy announcement, “while the NIH anticipates that that there will be challenges associated with implementation, we expect these to be short-lived. Once the transition to the new way of operating is made, the benefits of widespread use of sIRBs will outweigh any costs and, ultimately, reduce burdens to the research process.”
In proposals submitted to the NIH, applicants will be expected to include a plan identifying the sIRB that will serve as the IRB of record for all study sites. It will be the applicants’ responsibility to assure that the sIRB is qualified to serve. NIH acceptance of the submitted plan will be incorporated as a term and condition in the award. Awardees will be responsible for ensuring that the authorization agreements between IRBs (“reliance agreements”) are in place.
According to the policy, “The additional costs associated with sIRB review may be charged to grants or contracts as direct costs, provided that such costs are well-justified and consistently treated as either direct or indirect costs according to applicable cost principles in the NIH Grants Policy Statement and the FAR 31.202 (Direct Costs) and FAR 31.203 (Indirect Costs).”
Before the policy takes effect, the NIH will be issuing guidance and resources to assist with implementation.
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:
The New England Journal of Medicine today published a perspective by NIH Deputy Directory Kathy L. Hudson, PhD, and NIH Director Francis S. Collins, MD, PhD, in which they outline the major reforms proposed for regulations governing the ethical conduct of research involving humans, known as the Common Rule (45 CFR 46, Subpart A).
The proposed changes are meant to enhance respect for research participants, calibrate oversight to level of risk, simplify consent documents, streamline IRB review, increase privacy and security safeguards, and facilitate broad participation in research.
“These long-overdue reforms will bring the Common Rule into the 21st century. They should help the scientific community take a giant leap forward in showing respect for research participants, without whom the biomedical research enterprise would cease to exist.”
The NIH is encouraging all stakeholders—the public, researchers, and patients—to closely review the proposed changes and participate in the comment process by the December 7, 2015, deadline.
In recent health information technology news, the University of California, San Francisco (UCSF), has received a 5-year National Institutes of Health award to support its launch of a cardiovascular mHealth platform. The research platform, to be named Health ePeople, will build on the successes of UCSF’s Health eHeart Study, which began in 2013. That study, with more than 30,000 participants worldwide, uses the power of mobile technologies to collect cardiovascular data and patient-reported outcomes (PROs) from study participants.
The Health ePeople platform will advance mHealth by providing researchers with easy access to a large cohort of volunteers, along with a quick, affordable means for collecting their health data through mobile and wireless technologies. Though the platform will not be ready to enroll new participants for several months, people who want to participate in the cohort can sign up through the Health eHeart Study website.
For information and short videos on mHealth technologies, visit the Living Textbook’s chapter on mHealth and PROs.
On September 17, the Precision Medicine InitiativeWorking Group presented to NIH Director Dr. Francis Collins a detailed design framework to advance the creation of a national, large-scale research cohort for developing more effective treatments tailored to individuals. The framework makes recommendations on cohort assembly, participant engagement, data, biological specimens, policy, and governance. The recommendations are based on a set of high-value scientific opportunities that were identified by the working group following extensive stakeholder engagement.
The NIH plans to move quickly to build the infrastructure so that participants can begin enrolling in the cohort in 2016, with a goal of enrolling at least 1 million participants in 3 to 4 years. Visit the NIH News & Eventswebsite for more details.
A recent article in Nature highlights the Precision Medicine Initiative, launched in January 2015 and spearheaded by the National Institutes of Health. Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person. This initiative will involve collection of data on genomes, electronic health records, and physiological measurements from 1 million participants. A main objective is for participants to be active partners in research.
But a major decision faced by the initiative’s working group is how much information to share with participants about disease risk, particularly genetic data. Though there is much debate in the field, the article suggests that public opinion on data sharing may be shifting toward openness.
The Precision Medicine Initiative working group will be releasing a plan soon. For details on the goals of the Precision Medicine Initiative, read the perspective by NIH Director Dr. Francis Collins in the New England Journal of Medicine.
Findings from the meeting, which include case study presentations and reflections from multiple stakeholders representing the research, clinical, and patient communities, were distilled into a summary document available from the NIH Collaboratory Knowledge Repository at the link below:
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.”