FEATURE
Show Us the Data !
“ We often perceive negative trials as a ‘ failure ’ ... but negative clinical trials are actually very informative .”
Clinical Trial Resources
For more details on the new data-sharing requirements for NIH-funded research and the new policy , visit osp . od . nih . gov / office-clinicalresearch-and-bioethicspolicy / clinical-research-policy .
NIH ’ s National Library of Medicine , which maintains ClinicalTrials . gov , has also produced a series of training webinars to introduce investigators to the key provisions of the rule . Visit clinicaltrials . gov / ct2 / managerecs to view the presentation and associated materials .
— GRZEGORZ NOWAKOWSKI , MD
faster than ever , and we need to stay on top of it .”
To meet the timeline , he explained , investigators will need additional support from fellow investigators and data analysts to prepare and report findings .
But , Dr . Cortes noted , certain aspects of trial analysis are out of the investigators ’ control , and these external factors could make it difficult to meet the 12-month mark . “ From the last data point generated , many things have to occur before we are able to publish data in a reasonable , clean , clear , and accurate way ,” he said .
This could be particularly challenging for trials that necessitate a greater level of coordination among involved parties , such as multicenter studies or studies conducted with the pharmaceutical industry .
“ I am involved with a number of studies with pharmaceutical industry partners , but I could not publish the results because I only have my own patients ’ data ,” he said . “ Taken alone , these results aren ’ t meaningful .” However , Dr . Cortes agreed that having some semblance of a deadline is important to keep investigators accountable for sharing results .
Dr . Wolinetz said NIH arrived at the 12-month deadline after considering public comments received during the HHS ’ rule-making process . The formal rule allows for a delay in reporting of up to 2 years if a certification is submitted in the case that either “ an unapproved , unlicensed , or uncleared product studied in the trial is still under development by the manufacturer or that approval will be sought within one year after the primary completion date of the trial for a new use of an approved , licensed , or cleared product .”
Extensions could also be granted if there is “ good cause ” for the delay , and investigators could apply for a permanent waiver in extraordinary circumstances .
“ We want to strike the balance between wanting to get the information out there in a reasonable amount of time , and recognizing – particularly for industry sponsors of clinical trials – that certain business practices could be problematic to that timeline ,” Dr . Wolinetz said . Although Drs . Nowakowski and Cortes believe that researchers will ultimately be able to meet the tighter timeline , they say one of the biggest challenges will come before a trial is under way : Compiling the data-sharing plan .
“ There is no question that this new facet adds to the administrative burden and , unfortunately , everything we do now is increasingly becoming more burdensome ,” Dr . Cortes said .
According to Dr . Nowakowski , the datasharing plan is the aspect of the new rule that investigators are “ least enthusiastic about .”
Many researchers , he added , felt that the requirement to share clinical findings within the designated timeframe was sufficient to improve the value of clinical trials . Many variables go into the planning , development , and execution of a clinical trial , he noted , and those can be difficult to predict at the start of a trial .
That lack of enthusiasm is caused , in part , by uncertainty about what exactly NIH will require of data-sharing plans . Dr . Wolinetz said NIH is working to develop an organization-wide data-sharing policy that will expand on current guidance for data-sharing plans and outline what types of databases to use , which metadata to attach , in what format the data should be presented , and how long the data will be available .
“ We are at the point now where we are trying to be very thoughtful about how we take this data-sharing plan and move into the next phase of specific policy ,” she said .
Dr . Meropol said that deciding how to communicate outcomes data and determining the most valuable information to other stakeholders will also be challenging .
“ The language used for communicating study implications with a lay audience is much different than the language used to communicate results with a scientific audience ,” he said . “ There is a fine line between a dispassionate summary of results and marketing . This factor needs to be carefully considered and monitored .”
Great Expectations
For larger research institutions that were already subject to NIH ’ s 2003 data-sharing policy , there may not be substantial changes to existing practices , but for researchers applying for smaller amounts of funding , adapting to the new policies will require a significant shift in practice .
“ The new ruling has expanded the requirements somewhat , but not dramatically ,” Dr . Meropol said , adding that his cancer center has been providing data-sharing plans and sharing trial outcomes for several years . “ For many sites , this will be a wake-up call .”
The researchers who spoke with ASH Clinical News agreed that a broad educational effort could help prepare investigators to meet the new expectations ; it could involve continuing medical education activities or online resources or , as Dr . Cortes suggested , a simple , straightforward outline of what investigators need to do at each step of the process , from grant application to final reporting .
The education extends to NIH staff , according to the viewpoint article published in JAMA . “ As a crucial first step , NIH will require Good Clinical Practice ( GCP ) training for investigators and NIH staff responsible for conducting or overseeing clinical trials ,” Dr . Hudson and co-authors wrote . “ The aim is to help ensure that all involved in the clinical trial enterprise have the appropriate knowledge about the design , conduct , monitoring , recording , analysis , and reporting of clinical trials . While GCP training on its own may not be sufficient , it provides a consistent and high-quality standard .” 5
Dr . Wolinetz pointed to several instructional webinars available on ClinicalTrials . gov to guide investigators through the HHS final rule , complementary NIH policy , and what it all means for their research ( SIDEBAR ).
Researchers can also learn from each other , Dr . Meropol added , by reporting best practices and strategies for complying with the regulations in the most efficient manner – and in the way that is most valuable to the public .
Investigators are not the only ones who could stand to benefit from this extra layer of education . Informing academic centers of the new obligations could help research institutions ensure that investigators are given enough flexibility and time to meet the new reporting requirements , according to Dr . Nowakowski .
A Step Forward
Regardless of the obstacles to implementation and the steep learning curve many investigators may face , the recent actions to promote widespread data sharing represent a move forward for science .
Similar practices are being adopted across the world . For instance , in the Netherlands , although there is no formal government obligation yet , several of the funding agencies supported by the government have made data-monitoring plans , including data sharing , a compulsory requirement to secure funding . The European Union also recently expanded the scope of its Horizon2020 program to include research in all areas covered by the program to promote data and knowledge integration . Researchers can opt out at any stage if there is a reason not to comply , but those who opt in must submit a data-management plan similar to the data-sharing plans outlined in the new NIH policy . 8
In the United States , some are hoping that NIH ’ s decision to create a specific data-sharing policy for all NIH-funded clinical trials will set the tone for the research community . “ I wish there were a mandate like that for every study – not just NIH-funded studies ,” Dr . Cortes said .
When investigators are forthright about the trials they have performed and the outcomes they have observed , researchers contend , everyone benefits .
“ This transparency allows people to see what others are doing and what they have found ,” Dr . Wolinetz said . “ It helps refine the design of future experiments , prevents redundant experiments , and helps improve reproducibility and vigor .”— By Jill Sederstrom ●
REFERENCES
1 . Department of Health and Human Services . 42 CFR Part 11 . Final Rule . Accessed April 5 , 2017 , from http :// s3 . amazonaws . com / public-inspection . federalregister . gov / 2016-22129 . pdf .
2 . National Institutes of Health . NIH Data Sharing Policy . Accessed April 5 , 2017 , from https :// grants . nih . gov / grants / policy / data _ sharing /.
3 . National Institutes of Health . Final NIH Statement on Sharing Research Data . Accessed April 5 , 2017 , from https :// grants . nih . gov / grants / guide / notice-files / NOT-OD-03-032 . html .
4 . National Institutes of Health . Final NIH Policy on the Use of a Single Institutional Review Board for Multi-Site Research . Accessed April 5 , 2017 , from https :// grants . nih . gov / grants / guide / notice-files / NOT-OD-16-094 . html .
5 . Hudson KL , Lauer MS , Collins FS . Toward a new era of trust and transparency in clinical trials . JAMA . 2016 ; 316:1353-4 .
6 . Ross JS , Tse T , Zarin DA , et al . Publication of NIH funded trials registered in ClinicalTrials . gov : across sectional analysis . BMJ . 2012 ; 344 : d7292 .
7 . Piller C . Law ignored , patients at risk . STAT . Accessed April 5 , 2017 , from https :// www . statnews . com / 2015 / 12 / 13 / clinical-trials-investigation /.
8 . European Commission . H2020 Programme : Guidelines on FAIR Data Management in Horizon 2020 , July 26 , 2016 . Accessed April 6 , 2017 , from http :// ec . europa . eu / research / participants / data / ref / h2020 / grants _ manual / hi / oa _ pilot / h2020-hi-oa-data-mgt _ en . pdf .
32 ASH Clinical News June 2017