FEATURE for science policy and director of the Office of Science Policy at NIH , told ASH Clinical News . Offering this information to the public is a way to “ maximize the value of our investment in these trials ,” she added .
“ As a principle , the public sharing of clinical trial results is a great thing that serves the public good ,” agreed Neal J . Meropol , MD , associate director for clinical research at the Case Comprehensive Cancer Center at Case Western Reserve University . “ Over the years , many clinical trials are conducted , but their results are never published . It ’ s a waste of money and effort , and it is disrespectful to the volunteers who participate in clinical trials .”
Although many in the research community have praised the new policy as a step forward for research and innovation , investigators who spoke with ASH Clinical News acknowledged that instituting the requirements will yield a new set of challenges and add to the administrative burden already facing investigators .
Reforming Clinical Trial Practice
NIH has long been a proponent of open data sharing , but this new policy expands the scope of its existing data-sharing policy , which went into effect in 2003 . 3 The original policy was much broader and required that researchers submit a data-sharing plan only if they were applying for more than $ 500,000 in funding during a single year .
“ The 2003 rule was only applicable to very large awards and was fairly minimal in terms of the stipulated details ,” Dr . Wolinetz said . The new policy provides more details on the how and when of data-sharing compliance .
Now , for any research effort that falls under NIH ’ s definition of a “ clinical trial ” and is either wholly or partially funded by NIH , investigators will be asked to submit a data-sharing plan that outlines how they will disseminate and share the study ’ s outcomes . Trials must be registered on ClinicalTrials . gov within 21 days of enrolling the first participant ; then , after the trial is underway , investigators will be required to publish the results on ClinicalTrials . gov within 12 months of collecting the last data point – regardless of whether the trial resulted in a positive or negative outcome .
The new regulation also has teeth : “ NIH will withhold clinical trial funding to grantee institutions if the agency is unable to verify adequate registration and results reporting from all trials funded at that institution .” 1
If researchers fail to meet the demands of the new policy or regulation , they could face significant consequences . Those who do not comply with the registration and reporting rules , or provide false or misleading clinical trial information , will receive a warning and an opportunity to remedy the non-compliance within 30 days . Failure to do so will result in the researcher being subject to an additional civil monetary penalty of “ not more than $ 10,000 for each day of the violation ” until the violation is corrected . 1
Falling short of the requirements could also hinder future efforts to secure funding , Dr . Wolinetz said . “ If a non-compliant institution applied for funding , we could have to consider whether or not it would be appropriate to give it another award for a clinical trial .”
The data-sharing policy is just one recent action by NIH to reform clinical trial practice . The agency also decided that it will not accept unsolicited clinical trial applications ; instead , a new policy requires that all clinical trial applications be submitted in response to a specific Funding Opportunity Announcement . Additionally , on June 21 , 2016 , NIH issued a policy that calls for the use of a single Institutional Review Board ( IRB ) for multisite trials to eliminate duplicative review and to streamline the IRB review process . “ The shift in workload away from conducting redundant reviews is expected to allow IRBs to concentrate more time and attention on the review of single-site protocols , thereby enhancing research oversight ,” according to the text of the final rule . 4
“ Our hope is that , taken together , all of these things will ultimately improve the way clinical trials are conducted – from conception through funding through conduct ,” Dr . Wolinetz said .
Shining a Light on Hidden Data
In a recent viewpoint article published in JAMA announcing the new policy , NIH policymakers outlined several benefits of improving access to information about clinical trials , including physicians , patients , and family members being able to more easily find relevant information . 5
“ It is possible that increased registration of clinical trials could aid recruitment , reducing the number of trials that fail because they do not meet their enrollment targets and thus do not have the statistical power to give meaningful results ,” wrote Kathy L . Hudson , PhD , deputy director for science , outreach , and policy at NIH , and lead author of the article .
“ Although the process of enhancing the clinical trial pipeline may be a work in progress , the goal of these varied activities remains constant : to maintain public trust and to encourage advances in the design , conduct , and oversight of clinical trials ,” Dr . Hudson and co-authors wrote in JAMA . 5 “ These innovations are intended to help NIH better fulfill its mission of supporting scientific discovery to improve human health , while elevating the entire biomedical research enterprise to a new level of transparency and accountability .”
The policy also addresses one of the biggest concerns with clinical trials today : Many results never see the light of day – leaving gaps in the knowledge base of researchers , clinicians , and patients .
For instance , a 2012 study looked at NIHfunded trials registered on ClinicalTrials . gov between 2005 and 2008 and found that just 46 percent of the trials ’ results had been published in a peer-reviewed biomedical journal within 30 months of completion . 6 By 51 months , that number had climbed to 68 percent , but that still leaves nearly one-third of results unpublished .
In 2015 , a STAT investigation identified multiple prestigious research organizations that routinely failed to report trial results , violating a 2008 law issued by the FDA . 7 The reporters found that four of the top 10 recipients of federal medical research funds from NIH – including Stanford University , the University of Pennsylvania , the University of Pittsburgh , and the University of California , San Diego – either never disclosed trial results or did so late 95 percent of the time .
Grzegorz Nowakowski , MD , associate professor of oncology and medicine in the Division of Hematology at the Mayo Clinic , said one reason results are underreported is the bias to report only positive trial outcomes . “ We often perceive negative trials as a ‘ failure ,’ and we tend to shy away from those , but negative clinical trials are actually very informative ,” he contended . “[ Negative trials ] may not change clinical practice , but they do inform the science quite a bit .”
Jorge Cortes , MD , deputy chair of the Department of Leukemia at the MD Anderson Cancer Center and a Jane and John Justin Distinguished Chair in Leukemia Research , agreed that even negative studies , or those in which a hypothesis was not validated , were initially conducted for a reason .
“ We thought there was some good preclinical work , there was some important background that justified it to be done , and sharing that information will help the next studies ,” he said . “ It will help the development of preclinical data , new studies , and new drugs or interventions of a similar nature .”
Failing to report negative outcomes , Dr . Nowakowski added , hinders clinical research and can have serious implications for clinical practice . He noted that it is common for eager clinicians to put promising outcomes from phase II studies into practice before more robust phase III trials are conducted . If the phase III trial fails to support the use of the drug regimen or intervention but those results are never reported , clinicians could be using ineffective – or , in some cases , dangerous – therapies .
In the STAT investigation , reporters found that investigators failed to report data for two trials of the experimental anticancer drug ganetespib , even though “ the results of tests involving breast and colorectal cancer patients showed serious adverse effects in 13 of 37 volunteers ,” including one death . 7
“ Particularly in the field of lymphoma , several large phase III trials were presented with negative results , and many of the control arms or experimental arms in those trials included interventions that were already being used in clinical practice based on encouraging phase II results ,” Dr . Nowakowski said .
A Bigger Burden to Bear ?
The benefits of the policy seem apparent and abundant , but putting it into place will not be easy .
The new timelines are the biggest source of concern for investigators on federally funded clinical trials . With just 12 months between collecting their last endpoint and reporting their results , some researchers believe that this aggressive timeframe will require them to rework their typical post-trial analysis .
“ It ’ s going to require some more effort and will put some strain on our systems , but it ’ s something that we need to adapt to ,” Dr . Nowakowski said . “ The field is changing . The pace of progress is
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