Retaining reader value in plain language summaries of clinical studies

From 2019, sponsors of clinical research will need to prepare plain-language summaries (PLSs) for all phase 1-4 interventional trials, to fulfil requirements for greater transparency under EU Clinical Trials Regulation 536/2014 (EU CTR Article 37).

It’s an obligation that carries some challenges. If the summaries are too simplistic – in the attempt to cater for a very broad public readership – they could be misleading to some readers, creating risks for sponsors.

The European Medicines Agency (EMA) has proposed that the plain-language round- ups of the key findings and conclusions appeal to readers with very limited health literacy. So firms must decide what should be included and how best to explain it, as well as what should be left out in order not to lose the least knowledgeable reader.

Sponsors are understandably keen to ensure that these documents do justice to the original studies, however. During early attempts at these summaries, study teams have been seen to push back against the proposed wording and selective content, worried that it could alter the emphasis or be taken out of context.

Self-assessment

Significantly, the EMA has not articulated any plans to scrutinise the summaries issued for publication. This places the onus on companies themselves to ensure that the summary documents do their job effectively without being misleading. This also applies to every market in which the drugs are being sold across the EU – requiring accurate local-language versions of each document.

The overriding challenge for study teams is not that the EMA’s PLS requirement will create a lot of additional work (although it most certainly will), but rather that the task falls outside their area of skill and experience. Previously their output has been almost exclusively for a scientific audience; they are not accustomed to presenting their findings to readers who do not share the same base understanding. The last thing they want is for the simplified summaries to be a weak point and reflect badly on their research.

Sponsors are reacting to the situation in a number of ways. Some are creating the summaries to meet the minimum requirements from the EMA. They want to avoid being accused of cherry-picking the secondary endpoints they include or skewing the impression the reader takes away from the PLS. Others instinctively want to add more detail. But this could lead to long and unwieldy summaries, which miss their intended purpose.

Practice makes perfect

For now, summaries are being produced voluntarily and applied to already- completed clinical studies. Although these scenarios may lack the urgency that will be present when PLSs become a more formal requirement, they do provide a good testing ground. They also present some practical questions about how these retrospective

PLS documents will be distributed to participating subjects, for example.

Other, ongoing logistical challenges include the need to establish standard operating procedures (SOPs) for handling and processing PLSs, and to build templates for forming the content. Designated teams will need to be trained too, so that they can more tangibly appreciate how the summaries will be used, the right balance of what to include and how best to pitch it for a public audience.

To help with this last point the EMA has proposed that, early in the development of a PLS, sponsors engage with patients who can provide early feedback about the documents and their content, and their framing and wording. In the case of local- language versions for other countries, it is also advisable here to test the translations with local audiences. Although translation tools can help with getting the phrasing right in another language, the only safe way to quality-check local versions and ensure individual dialects and cultural meanings are taken fully into account is to perform bidirectional translations, and confirm that nothing has been lost in the process by asking those on the ground in each target country.

As a final point, it is not just the EU that is moving towards greater public transparency. The US FDA has also issued a draft document for consideration in relation to equivalent measures, so it is possible that measures ironed out now will serve firms more broadly in time.