One of the biggest frustrations for clinical trial sponsors is that a fully funded trial can be cancelled for the simple reason that it can’t find enough patients. Low awareness combined with strict parameters can leave investigators drawing from a shallow pool, and eligible participants are unlikely to get on board if they don’t understand the trial process. Until recently, EU transparency regulations have stipulated only that patients have the option to be informed of the results of trials they participate in. That didn’t cover how the information is disclosed, whether it should be available to a wider audience or how to provide trial summaries in lay people’s terms.

That’s changing with the introduction of the European Medicines Agency (EMA)’s Policy 70 on the publication of clinical data for medicinal products for human use. It requires European clinical trial reports, including patient narratives, to be proactively disclosed on a public web portal. To smooth the process, the EMA has released guidelines on exactly how to edit reports for public release. They must strike a fine balance between transparency and protecting sensitive information.

Merete Jørgensen, senior trial disclosure director at Novo Nordisk, calls the implementation of Policy 70 “the biggest challenge within clinical transparency.”

“In contrast to what many people might think, the biggest hurdle for industry is not the protection of business-critical information,” Jørgensen says. “The challenge is to ensure that we safeguard the personal data of the people who participate in our studies while still maintaining the utility of the disclosed information.”

Policy 70 has technically been effective since 2016, but the web portal where reports will be posted is not expected to launch until 2019. Previously, the only official European guidance regarding lay summaries came from the Declaration of Helsinki, which stated: “All medical research subjects should be given the option of being informed about the general outcome and results of the study.” This process is often left to investigators because of the need to avoid promotional language, but Policy 70 puts the onus on sponsors to communicate their results.

“We welcome the new regulations, including Policy 70,” Jørgensen says. “This will solve some of the challenges as well as practicalities, as trial sponsors and investigators will not need to keep track of the contact information for the trial participants in order to communicate the results.”

Policy 70 follows the European Commission’s Clinical Trials Regulation 536/2014: Transparency and publication of clinical data, which is now set to come into effect in 2018 after several delays. Article 37 of the regulation requires sponsors to provide laypersonfriendly summaries of trial results. The aim is “to create an environment that is favourable to conducting clinical trials in the EU, with the highest standards of safety for participants and increased transparency of trial information.”

Linked recommendations released in January 2017 outline how to write those summaries, covering everything from writing style to font colour. They end with advice for sponsors to provide investigators with trial results to send to participants, so they know they’re appreciated.

Striking the balance

But the new rules don’t go far enough, according to Behtash Bahador, senior manager for quality, compliance and communicating trial results at the Centre for Information and Study on Clinical Research Participation (CISCRP). A US-based non-profit working with trials around the world, CISCRP aims to bridge the gap between participants and researchers in hopes of engaging the public and improving patient satisfaction.

“Repeatedly, what we hear from patient advocate groups is that they just don’t see a way that sponsor organisations can independently ensure that the summaries that they are producing are entirely non-promotional,” says Bahador. “Just posting it on the regulatory website doesn’t necessarily mean you have regulatory oversight on that document.”

Bahador’s view is that Policy 70 doesn’t provide sponsors with enough guidance. It emphasises the new online portal as a major development in transparency and disclosure, but Bahador says the practicalities of delivering results to patients were never the main problem.

“In our experience, it’s a really fractional percentage that it adds to the cost of a study to print and send these materials out to study sites,” he explains.

In his opinion, the existence of the portal could mean a drop in the quality of patient communication. As sponsors adopt a onesize- fits-all solution, vulnerable patients such as children and those who are not digitally literate could miss out.

“There are sponsors who are looking at this as just a checkbox,” he says. “Posting to an online portal is not going far enough. Patients should at the very minimum have the option of receiving a printed copy of the results.”

Several companies already upload their trial results to a data-sharing portal, according to Barbara Kress, executive director of clinical data disclosure and transparency at Merck. Proceedings for the 2015 Promoting Clinical Trial Data Transparency Conference report that Kress said Merck “has its own data request portal, which started in 2012 for investigator interaction”. However, she added that “Merck prepares data on demand, not proactively,” and the task was left to a single staff member. At the time, Merck was “still waiting for standards to be established”.

Jørgensen says Novo Nordisk already posts lay summaries on a public website at the same time as the clinical trial reports of a more scientific or regulatory nature are made available. The reports on the proposed EU portal are meant not only for investigators and the public but also for academics and other sponsors. Sponsors must now anonymise and redact each report to protect personal and businesscritical data. Jørgensen says this could be counterproductive to increasing trust.

“With Policy 70, EMA is requiring documents submitted to regulators to be disclosed to the public and at the same time asking the industry to adopt new methods for protecting personal data,” she explains. “The new methods include slightly changing information in the original documents that could be used to identify individuals while still maintaining the conclusions and results.

“It is a challenge to communicate more generally that such changes to the information do not alter the information or level of transparency.”

Not only that, but Bahador says patient welfare is also at stake when sponsors communicate directly with participants. “There is a potential for misunderstanding,” he says.

“For example, overstating the effects of an already approved medication, particularly if that trial’s looking at an off indication. If you are misrepresenting the results in a way that’s going to be misleading, people have the ability to go out and get that drug because it’s approved already.”

When oncology and life-threatening illnesses are involved, participants may see clinical trials and new treatments as a worthwhile long shot. They’re highly invested in the outcome and ready to take swift action if results look promising.

“If you’re putting patients first, you don’t want them to have the wrong impression about the safety or the efficacy of a medicine that they were taking,” Bahador says.

This is one reason why sponsors often leave it up to investigators to communicate with patients. The other reason is that it requires a significant amount of business resources to do properly.

“Communicating with patients and the public in a way that’s understandable to them is an academic focus area all on its own,” says Bahador. “The sponsors that right now seem to be moving towards having these summaries done completely internally are unaware of the fact that you need to have experts in health communication, health literacy and general patient communication.”

The same goes for the edits required for published reports under Policy 70.

“The clinical documents in a Marketing Authorisation Application must now be submitted three times,” says Jørgensen. “In addition to the original application, the suggestion for a redacted and anonymised text must also be submitted, and once agreed with EMA the finalised documents are to be sent in a third submission.”

Increasing awareness

The demanding nature of the task could come as a surprise to those who have left patient communication at the bottom of their priority lists.

Bahador noted a general lack of awareness when he attended the Fourth Clinical Regulatory Medical Writing Forum in July 2017 in Philadelphia.

“There was quite a bit of confusion on whether the regulation that requires lay summaries is part of EMA’s Policy 70 – which it isn’t, they are two separate things,” he says. “It was striking to learn that this is new to people; that the development of lay summaries of aggregate results of clinical trials is something that people weren’t necessarily aware of.”

Until now, implementation of the existing guidance was patchy and varied by country throughout the EU. Despite the extra effort required by the new regulations, Jørgensen says she welcomes their promise to bring the industry into line.

“In order to best serve the aim of transparency, a consistent and global approach to what is shared and when would be a benefit. It only takes one country that thinks a given piece of information is not confidential, and then it is not,” Jørgensen explains.

Bahador hopes to see more sponsors taking the initiative to improve on transparency and disclosure without the need for further mandates from the EU.

“It’s already a hyper-regulated environment,” he says. “The best way for lead sponsors is to get started right away. They need to not underestimate this undertaking.”

When sponsors learn to effectively disclose their results and communicate with patients, they contribute to an industry climate of trust. But for transparency to trickle down to participants and start to reduce the costs of cancelled trials, it needs buy-in from the entire industry. The point of Policy 70 is that it’s proactive: it requires posting trial reports before they’re requested. Those sponsors that take the lead in interpreting that guidance will be the ones who make the most of it.