Applied Clinical Trials
It’s time to establish standard practices to return clinical trial results summaries to patients.
Patients and the public are demanding higher levels of transparency and disclosure in clinical trials. And the
National Institutes of Health (NIH), other government agencies, and most pharmaceutical and biotechnology companies agree that the return of plain language clinical trial results summaries is the right and ethical thing to do. But, despite broad consensus around this important issue, at the present time only 2% of all clinical trials completed or terminated within the past three years have returned their results-in plain language- to their respective study volunteers.
There are a number of perceived barriers preventing most companies from piloting and/or establishing processes to return plain language summaries. Most of these barriers have already been addressed, however. Regulatory pressure mandating the return of plain language summaries is also intensifying. It is clear that government and industry research sponsors alike will place greater urgency and effort into establishing and standardizing plain language results communication practices over the next 18 months.
Five primary barriers
Articles in the peer-review and trade press-and anecdotal conversations that I’ve had with clinical teams, medical writers, and disclosure personnel through my involvement at the Center for Information on Clinical Research Participation (CISCRP)-highlight five perceived barriers to adopting plain language summary disclosure programs. They are:
These barriers have largely been addressed by research sponsors who are already voluntarily returning their clinical trial results summaries to patients. During the past eight years, CISCRP has worked with most of these commercial and non-commercial research sponsors to develop templates, operating processes, and standard practices. Frameworks and guidelines from organizations including TransCelerate, Clinical Trials Transformation Initiative (CTTI), and Multi-Regional Clinical Trials (MRCT) Center have also been created to help sponsors navigate uncertainty and establish practices.
Research sponsors have found, for example, that medical writing and disclosure functions can share resources and personnel to support plain language summary projects. Staffing depends on the volume of clinical trial activity in the portfolio. A few research sponsors have established capability in-house to create plain language summaries, while others are outsourcing this responsibility to contract services vendors. Performing this activity internally or under contract with for-profit medical writing services may be problematic, though. These relationships can be unduly influenced by the research sponsor’s unintentional, or intentional, efforts to publish plain language summaries containing biased or promotional information. This is especially true of for-profit medical writing providers with well-established, longstanding preferred provider agreements.
Implementation costs are relatively low and most sponsors are generally able to locate funds for pilot programs. But, due to delayed efforts for establishing which function will own the activity, continuity in funding for ongoing efforts is limited. Costs are highly dependent on the size and scope of each clinical trial and the number of translations (e.g., number of global investigative sites, number of study volunteers). With respect to the latter, typically research sponsors match the languages used in the informed consent form with those in plain language summaries. Once a plain language clinical trials results communication program has been established and begins to scale, however, process efficiencies help to lower the overall cost per program.
Production and distribution costs have also been raised as concerns. Plain language summaries are typically returned to study volunteers through the investigative site; study staff send printed reports using mail-ready envelopes. A few research sponsors have been testing the distribution of digital formats, including pdf, simple data files, and html, through online portals. However, some sponsors are concerned about compromising the study volunteer-study staff relationship and they have been reluctant to move away from print distribution.
Ethical review committees review and approve informed consent language, which typically includes notification to study volunteers that they will be receiving the results of their clinical trial. Ethical review committees also review any communications associated with the return of summaries provided to study volunteers while the clinical trial is underway (e.g., reminders and “Thank You” notes).
To avoid the risk of bias and promotional summary language, and to ensure that patient and public needs are met, CISCRP (an independent non-profit) convenes an objective and neutral editorial panel of patients, patient advocates, medical professionals, and consumer health communication experts. This is done for every new plain language summary.
Following receipt of the plain language summary report, most patients choose to review it with their primary or specialty care physician. It is rare that investigative site personnel are contacted to review the summary report one or more years after the clinical trial has ended. In those instances when site staff are consulted, reported time commitments average 30 minutes or less.
Regulatory issues and return on engagement
The ethical obligation to return clinical trial results summaries to patients in “accessible” language can be traced back to the 1964 Declaration of Helsinki. Some 33 years later, in 1997, the Food and Drug Administration (FDA) Modernization Act led to the creation of a government maintained clinical trials registry for listing later-stage interventional studies for serious and life-threatening illnesses. Then, in 2007, the FDA Amendments Act (FDAAA) mandated that later-stage efficacy studies and approved products report clinical trial results within one year after the completion of data collection or study termination for later-stage efficacy studies and for approved products. The law also established a provisional monetary penalty of $10,000 per day (for industry-funded studies) and the loss of grant support (for NIH-funded studies) for failing to comply.
In 2010, Congress signed the Plain Writing Act into law requiring federal agencies, including the NIH, to provide all communications to the public in plain, understandable language.
In 2017 the FDA Amendment Act Title VII Final Rule was issued to clarify the registration process and regulatory requirement for submitting clinical trial results information, to expand the definition of applicable experimental treatments falling under the mandate, and to require plain language communication of information contained in the informed consent document.
The European Commission established the European Clinical Trials Database (EuDRACT) in 2001. Eleven years later, the Commission issued Eudralex Volume 10 Guideline 2012/C 302/03, which required technical results summaries for all clinical trials conducted by at least one European member state to be posted on the EUDRACT databank within one year after completion.
In 2014 the European Commission issued Regulation 536/2014, reinforced by the European Medicines Agency’s (EMA) Regulation 007, to clarify the posting process on a new platform (EU Clinical Trials Register), expand the definition of trials to be registered, and to require that summaries be written in lay- or plain language. This most recent regulation is expected to go into effect toward the end of 2019 or in early 2020.
With respect to return on engagement initiatives, several published studies suggest that higher levels of patient engagement are achieved when study volunteers receive plain language clinical trial summaries. A 2018 Tufts Center for the Study of Drug Development (CSDD)–Drug Information Association (DIA) study found that the return of plain language summaries is among a small set of patient engagement initiatives that offer a measurable return on investment due to their relatively low cost and positive impact on study volunteer experience and retention rates. And a 2017 study by CTTI, with support from Tufts CSDD, found that improvements in recruitment and retention due to patient engagement initiatives, including the return of plain language results summaries, significantly increased the expected net present value of a clinical program.
In a global survey among more than 12,000 patients, CISCRP found that the promise to return a general clinical trial results summary is among the top five most important factors influencing a study volunteer’s decision to participate. And among 2,194 clinical trial volunteers who had completed their participation, the return of plain language results summaries had a positive, statistically significant impact on their perceptions, experiences, and overall satisfaction.
Gearing up for implementation
Although research sponsors are piloting initiatives and a small number are implementing broader programs, the ethical obligation to return plain language clinical trial results summaries to study volunteers is not embraced by the clinical research enterprise. Overall low levels of support and adoption reflect poorly on the enterprise as a whole, harm efforts to engage patients as partners in the clinical research process, and raise public and patient concern and mistrust in the research professional community.
A growing number of commercial and non-commercial sponsors will increase their efforts to return plain language results in anticipation and preparation of mandates and their enforcement.
Regulation requiring government agency support is already in place but requires harder deadlines and incentives to facilitate more rapid adoption. EU and North American regulation of pharmaceutical and biotechnology companies is tightening and enforcement may become more commonplace. Industry reputation is also tenuous in the current political environment made worse recently by widespread price increases of marketed drugs.
It is in the clinical research enterprise’s best interest to support initiatives that strengthen its relationships with patient communities and the public. The return of plain language summaries reassures patients that sponsors intend to be fully transparent, regardless of the study outcome, and is an important way to demonstrate a commitment to these valuable and highly valued partnerships.
Ken Getz, MBA, is the Director of Sponsored Research at the Tufts CSDD and Chairman of CISCRP, both based in Boston, MA. email: firstname.lastname@example.org