Building trust with clinical trial participants is critical to the success of drug development programs. One of the best ways to earn that trust is by meeting their expectations regarding learning study results. In fact, a 2015 study by the Center for Information and Study of Clinical Research Participation (CISCRP) showed that 73% of clinical trial participants want a summary of their study results (the plain language summary). That same study also indicated that receiving these results helps meet participant expectations which in turn increases their likelihood of sharing their trial experiences. This positive cycle of patient engagement increases trust in research and interest in future participation.
However, the current transparency and regulatory environment creates an unintended dichotomous view that pits meeting patient needs against satisfying transparency and regulatory requirements. In this blog post, I’ll discuss a model that balances these seemingly competing interests.
The current regulatory environment for plain language summaries
Both the European Union (EU) and the United States have issued regulations regarding plain language summaries. The EU Clinical Trials Regulation, which will become effective in 2019, requires a layperson summary for all Phase 2–4 interventional trials. Sponsors must post these summaries to the EU portal within 12 months of the end of the clinical trial. A lay summary is required in each of the local languages where the trial occurred in the European Union.
In the United States, the final rule on clinical trial registration and results information submission does not require submitting technical or non-technical summaries. The rationale was concern regarding ensuring that the summaries would be consistently objective and non-promotional. However, they have acknowledged that industry efforts to return results to participants may be informative to the department of Health and Human Services. And, they will review these efforts to evaluate the feasibility of requiring plain language summaries.
Demonstrate a commitment to patients, not just meeting regulatory requirements
Programs providing lay language summaries of trial results have typically been designed to meet the needs of the volunteers that participated in the study who want and deserve to learn these results. Yet, the draft guidance from the EU on the development of summaries clearly states, “Develop the summary for a general public audience.” This complicates the task for summary creators.
Principles of health communication tell us to know and engage the target audience. With the introduction of the EU Regulation, we now must write for both members of the general public with no prior knowledge of a trial while also creating a plain language summary that satisfies the needs of trial participants. One challenge we face is the need to convey appreciation to study participants. This is one of the most important elements of communicating with patients. But, how can we engage participants with this message when the summary is written for a general public audience?
Additionally, user testing of our lay summary template revealed the need for a section about the study design and schedule. This information helps engage readers to ensure better understanding of clinical trial designs. For study participants, this information reminds them of study procedures which took place a year or more prior. Importantly, this also provides a base of knowledge which aids in understanding trial results. Yet, this information is not explicitly required by the EU’s lay summary template, which is meant for someone without prior knowledge of the trial.
Another challenge is the need for complete reporting of information to avoid perceptions of withholding important findings while also sharing only the most scientifically supported results to avoid misinterpretation of the validity or applicability outside of the context of a single trial. In a summary intended for lay audiences, this must also be done as succinctly as possible. Unfortunately, omitting information that could be of interest to patients or the general public is often justified with the rationale that a link to the full results is provided. This attitude contravenes the tenets of health communication. The full trials results are technical. They’re nearly impossible for lay audiences to understand. Thus, linking to full results is a strategy that must be carefully utilized; it is not a catch-all.
Given all of these concerns, summary creators strictly following the EU requirements and guidance can miss the mark both on engaging readers and effectively achieving understanding of the trial results. The visual presentation of the lay summary (ie, design and formatting) is an important element that adds engagement and educational value, but there is no mention of this in the aforementioned EU guidance. The best way to ensure a lay language summary meets these critical goals is to involve patients and patient advocates in the development process. While available guidance indicates this best practice in health communication can be implemented during template development, each and every lay summary produced by CISCRP in coordination with Synchrogenix is reviewed by these essential stakeholders. It is not only feasible to do this, but it is a requirement from the perspective of advocates and even sponsors. Producing non-promotional and easy-to-understand summaries of trial results can only be accomplished through a process that addresses the challenges noted above and the many more that arise with each development project.
Writing lay language trial results summaries
Using patient-friendly language is becoming more and more of a priority for us. A challenge of writing plain language summaries is how to write in this language and also stay true to the scientific basis of a study.
We have to balance what is interesting to patients and what is interesting to scientists. Patients want to know whether a drug is a safe and effective treatment for their disease. In general, they want “black and white” answers.
Researchers want to explain the results of clinical trials in a precise and often nuanced way. They aren’t comfortable making black and white conclusions. Their conclusions contain many caveats: we tested this drug in a particular setting with a specific population. It may be safe and effective in these conditions. And a “shades of grey” conclusion is unsatisfying to the patient.
Can we write statements that would be more satisfying to patients? For instance, “this new treatment is better than the standard of care” or “this treatment ameliorated the disease symptoms”?
These statements address the patient’s interests. However, they are promotional and, frequently, inaccurate. This is because an approved drug’s label claims are not just based on one trial. They are based on evidence collected across multiple trials. So, we can’t provide patients with “black and white” trial results.
Compounding this challenge is scientists’ use of technical language to describe drug development. Pharmacokinetics. Antibody. Crossover study design. This technical language is incomprehensible to the general public. How do we develop a scientifically valid, plain language translation of a study that satisfies both the scientist and the patient?
Writing to communicate with a lay audience
One idea is to keep the language understandable to a lay audience by writing to the 6th–8th grade level. Therein lies another challenge! The information that is considered “6th–8th grade” varies greatly even between schools in the same district.
Both the NIH and EU provide guidelines on writing using plain language. Some non-governmental groups like TransCelerate also provide guidelines regarding health literacy principles. While these tools help us to understand the spirit of what that middle ground looks like, none of them are an absolute solution.
For example, both the CDC and the University of Michigan provide glossaries of plain language terms. But there is no standardization in this field. Thus, different plain language suggestions can be provided for the same scientific term. So, to discuss “interventions,” do you use the CDC’s recommended terms (“action, treatment, or program”) or the University of Michigan’s (“care”)?
Say, you’ve used these guidelines and glossaries to write a plain language summary. How do you know that a patient will actually understand it? Many people rely on readability metrics. The Flesch-Kincaid—based on word and sentence length—is most frequently referred to in this space. But, using readability metrics also poses challenges.
For example, using longer words and sentences is sometimes necessary. For example, “fever” is a concise lay substitution for “pyrexia.” But, what if your study involved a drug for respiratory syncytial virus? In this case, a longer explanation (“a virus in the airways that can cause pneumonia”) is the clearest.
The iterative process of writing lay summaries
Sponsors often struggle to write these documents. The first struggle involves scaling up their plain language summaries program to satisfy new requirements. To address this challenge, the clinical operations team often creates a master template that incorporates the regulatory requirements into the summary.
However, this isn’t an ideal solution because each team wants to write the summaries using their own specific language. Thus, to achieve scalability, we recommend educating study teams about plain language writing, not using templates. Create ownership expectations with the group that is authoring the summaries.
Consistency is also critical. You need to present patients with the same messaging from study to study. To do this, seek agreement on therapeutic area language, study design approach, etc. Creating messaging consistency makes lay summaries easier for patients to understand.
Telling the story of a clinical trial
It’s human nature to want to tell stories with a clear narrative arc. But, sometimes the desire to tell a compelling story can skew the balance.
For example, a company was doing a safety and pharmacokinetics (PK) trial in a specific disease. As they were conducting the trial, they found interim exploratory results suggesting the drug was effective. The team writing this trial’s lay summary wanted to stress these efficacy findings because they felt that this information would interest patients. However, the trial’s primary outcomes were for safety and PK. So creating that kind of patient communication becomes promotional as the efficacy claims wouldn’t have adequate statistical power.
Our best practice is to use regulated documents, such as clinical study reports (CSRs), as the source for plain language summaries. This ensures that the results we share with patients agree with the intent and design of the study. Moreover, we work with sponsor teams to set expectations as to the regulatory requirements for summaries.
Including the patient’s voice in regulatory documentation
We have an ethical imperative to consider the patient’s perspective in designing studies. Consider this scenario: Company X writes an informed consent form (ICF) that includes potential biomarker analysis of additional patient blood draws.
From the patient’s perspective, they’re getting pricked many times. But these biomarker blood draws aren’t part of the study’s objectives, so they’re not reflected in the CSR. Thus, we don’t write about these blood draws in the patient summary and assume that the patients won’t wonder what all those needle sticks were for. That’s a dilemma because this is a big part of the trial from a patient’s perspective. We have to continue communicating the purpose of the trial and provide clarity around what happens to the patients.
We must include the patient’s voice throughout the clinical study process. Starting with the study design, are we performing only the necessary assessments? Are we using technology like modeling and simulation to minimize blood draws? Can we avoid certain clinical trials completely, for example, using physiologically-based pharmacokinetic modeling to explore drug-drug interactions?
An overview of our recommended process
At CISCRP and Synchrogenix, we have established a process for our lay language summary programs. We start by setting expectations with the informed consent document, which informs the participants that they will receive the results of the clinical trial in an understandable format. CISCRP research has shown that 52% of patients said it’s very important to know if summary results will be provided before deciding to enroll in a trial. As the first touch point with participants, the ICF provides an opportunity to demonstrate your commitment to meeting patient needs. Next, CISCRP provides a “thank you” communication as participants leave the trial to remind them that they will receive the results and thank them for their role in advancing medical science.
For longer trials, we also provide brief communications once or twice annually to update participants on the availability of results. These communications are printed and sent to the investigative sites who then pass it on to their patients. Investigative sites appreciate this opportunity to strengthen their relationship with their patients.
We also use these communications to provide general education about the research process. The end of the process is providing the lay language summary to participants either in a printed format delivered to study sites or posted electronically to an online portal.
To learn more about the stable, transparent and reliable process for developing plain language summaries that we’ve developed through the Synchrogenix-CISCRP partnership, please read this white paper.