New year, new federal policies for clinical & translational research (2019)

22 Jan New year, new federal policies for clinical & translational research (2019)

Many researchers are tucking in to finish their first National Institutes of Health (NIH) grant proposals or IRB applications of the year. A number of changes to federal regulations and NIH policies relevant to clinical and translational research take effect in January 2019.

Revising the rule for human research protections

The Common Rule has been a fundamental part of clinical and translational research for decades. This set of regulations aims to provide protections for individuals participating in research conducted, funded, or regulated by several federal agencies. With so much university research funded by federal sources, institutional human research protection programs (HRPP) apply the Common Rule to almost all the research they review.

Changes to the Common Rule have been years in the making, aiming to modernize regulations, better protect research participants, and reduce burdens and delays for investigators. After delays, several new requirements take effect on January 21, 2019.

Thanks to expanded categories under the revised rule, more studies will be considered “exempt” and released from compliance with most human subjects regulations. In addition, continuing review will not be required for most studies involving minimal risk to participants. Your institution’s HRPP still determines which studies qualify for exemption.

The revised Common Rule also mandates several changes to informed consent. Key information to help participants understand risks, benefits, and alternatives to the research should be provided at the beginning of the consent process. Now, new elements, such as information about potential secondary research or a statement about possible commercial profit, will be required for certain types of studies. Additionally, after recruitment for a study closes, researchers will need to upload a copy of the consent form for federally funded studies to a public repository. Requirements for waiver of consent and waiver of documentation of consent have also been modified.

In some cases, state law or other federal agency regulations apply, and certain Common Rule changes will have a minimal impact on studies. To learn more about policies relevant to your work, check with your institution’s compliance unit.

Implementing policy changes for NIH applications

NIH has a host of recently announced policy changes that affect competing applications due on or after January 25, 2019. If you have been working on an NIH application, now is a good time to revisit the FOA and ensure that it remains active and relevant for your proposal. In fact, it’s always good practice to check funding opportunity announcements (FOAs) for updates periodically, including 30 days before the submission deadline. Policy changes and other modifications may be introduced via “Related Notices” linked to the FOA. As 2018 drew to a close, NIH also re-issued many parent announcements—broad funding opportunity announcements (FOAs) for investigator-initiated applications—incorporating revisions.

You will of course want to review relevant policies in detail, but here are some highlights.

Inclusion across the lifespan

Responding to Congressional directives in the 1990s, NIH implemented policies that require inclusion of women and minorities and children in NIH-funded clinical research. It is now broadening the policy on inclusion of children to inclusion across the lifespan. Investigators will either need to plan for participation of “individuals across the lifespan” (including children and older adults) or provide a scientific or ethical justification for exclusion on the basis of age. This policy applies even to research with human subjects that is considered exempt under the Common Rule.

Projects funded under the new policy will also need to provide different enrollment data for progress reports. Previously, NIH required aggregate tables reporting participant sex or gender, race, and ethnicity. Under the new policy, investigators will need to submit a spreadsheet containing de-identified data on sex/gender, race, ethnicity, and age at enrollment for each participant. Be sure that your data collection plans and informed consent documents permit submission of this data to NIH.

Updates to application instructions & review criteria

With changes to regulations and policies affecting grant-supported research, NIH and the Agency for Healthcare Research and Quality (AHRQ) have updated grant application guides and review criteria. Primarily, these involve replacing references to “inclusion of children” to “inclusion of individuals of all ages.”

NIH has also replaced the phrase “scientific premise” with “rigor of prior research. Originally, this was added to the Significance section of some applications in 2016 as part of an effort to improve reproducibility of NIH-funded research. Many applicants and reviewers were confused about what exactly it meant and how to address it. NIH has attempted to clarify by replacing the term with “rigor of prior research” supporting the proposal, including both published and preliminary data. Applicants will also be asked to “describe plans to address weaknesses in the rigor of the prior research that serves as the key support for the proposed project.”

Revised application guides are already available online. Currently they have information for applications due before and after policy changes take effect. Be sure to following the instructions relevant to your submission deadline.

New study type category for basic research involving human participants

Just a year ago, NIH rolled out new policies to improve accountability and transparency of clinical trials it funds, including new training, registration, and reporting requirements.

NIH defines a clinical trial as “a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.” This definition is very broad and includes some studies that meet the federal definition of basic research, which aims to build fundamental knowledge “without specific applications towards processes or products in mind.”

Many researchers were concerned about applying clinical trial policies to basic research involving human participants. Last summer, enforcement of registration and reporting requirements were delayed. As 2018 came to a close, NIH delimited a new study type, “Basic Experimental Studies with Humans” (BESH), with specific FOAs.

BESH are studies meeting both the NIH definition of “clinical trial” and the federal code definition of “basic research.” A key element is the lack of “specific application”, with some guidance provided in the FOAs (see the parent BESH R01 FOA, for example). BESH can use interventions to probe “fundamental aspects of phenomena”, for instance, but evaluating the intervention’s mechanism of action would fall under Clinical Trial Required or Clinical Trial Optional FOA.

The review criteria for BESH and Clinical Trial applications are essentially identical. The major difference is in award administration, where the ClinicalTrials.gov registration requirement has been removed for BESH FOAs along with reference to NIH institute or center (IC)-specific reporting requirements.

If your research involves human participants, you will need to figure out which category fits best. Consult with your IC program contact (see “Agency Contacts” section of the FOA) to verify you are submitting to the most appropriate FOA.

End of “Next Round Resubmission” to NIH for new investigators

The NIH review cycle time is a major rate-limiting factor for resubmission of applications. In 2007, NIH implemented a policy to expedite resubmission for new investigators who have not successfully competed for “substantial, independent funding” from NIH (e.g., an R01 or equivalent). Rather than waiting three or four months for the next standard deadline, new investigators could resubmit R01 applications 30 days after receiving their summary statement. The hope was that “next round submission” would accelerate the time to a first R01.

It turns out that few PIs took NIH up on the offer, and of the percentage of eligible investigators, those opting to resubmit early has declined over a decade. Furthermore there has been no change in the average age at which investigators get their first R01. Thus the next round resubmission policy is rescinded as of January 25, 2019. Summary statements for new investigators will still be prioritized, and new investigator R01 applications will be clustered for review within a meeting. The key difference is that new investigator resubmissions will be due at the same time as all other applicants.