Patient Engagement in Clinical Trials

What is patient engagement?

Simply put, patient engagement means getting patients more actively involved throughout the clinical research process. This can include bringing them on board as stakeholders in trial design, designing patient-centric protocols that are more enticing for participants and easier to complete, using interactive content, engaging with them with compassion and respect, and listening to and incorporating their feedback. Effective patient engagement works to improve recruitment, retention and adherence to the protocol, and patient satisfaction, and also to enhance rapport in general, leading to better perceptions and willingness to participate in future studies amongst the broader population. Patient engagement is a dynamic and interactive concept that, more than ever before, has become a critical factor that can make or break a study.

However, enhancing patient engagement requires various approaches, and without adequate forethought and smart strategies, clinical trials can struggle to recruit and retain patients. In this article, we provide an overview of various concepts that play into patient engagement in clinical trials, in hopes of equipping you with the right information to strategically boost patient engagement in your trials.

What factors influence patient engagement?

Numerous factors influence patient engagement in clinical trials, so the following topics should be taken into consideration when thinking about engagement strategies:[¹],[²]

• Motivation(s) for participating: Participants decide to take part in a clinical trial for different reasons; these motivations will directly influence their willingness to enroll and remain in a trial, as well as their degree of satisfaction and their experience. Patients may be hoping to access a novel treatment for their condition, may want to contribute to the advancement of healthcare in general, may wish to take a more active role in their healthcare, or might simply be curious to learn something new or find answers. Their first-hand experience during the trial may or may not match their original motivation, which will in turn influence the degree to which they remain engaged and interested in the trial.
• Study protocol and requirements: The study protocol - and what it requires of participants - is a significant factor in their engagement. On the one hand, the protocol should ideally be designed to be minimally burdensome for patients, i.e., reducing unnecessary travel time and difficult assessments/interventions. On the other hand, there should be enough touchpoints to keep the participants engaged with the study, making it evident that their participation is appreciated and that there is value in their completing the entire protocol. In other words, patients will ideally feel interested and actively involved in the trial, but not overwhelmed by it.
• Costs: There are various costs that participation in a trial may incur for patients. These costs can take the form of monetary expenses as well as time requirements, arising from things such as travel (fuel, parking, public transport), childcare, time off work, etc. If the trial begins to feel unmanageable amidst their other commitments, either in terms of monetary expenses or time commitment, the participant is more likely to leave the trial. Patient-centric trial design and compensation for participation are potential ways to address this issue.
• Quality and clarity of communication: Patients are more likely to feel engaged when their interactions with the trial staff/interface are clear and respectful. Patients should be able to understand the trial fully - including the reasons for the research, what is required of them, details of the intervention, etc. if they are left with any doubts, it should be easy enough for them to get those doubts clarified by a trial team member. It’s important to use clear language in all trial information presented to participants, from advertisements and outreach material through to consent forms and follow-up. Every interaction can be seen as an opportunity to improve the patients’ first-hand experience; compassion and enthusiasm amongst study staff can help participants feel seen and valued, increasing their personal engagement with the trial.
• Patient demographics: Socio-economic and geographical factors, such as neighborhood and social infrastructure, income level, age, sex, ethnicity, social circle, etc., can play into participants’ perceptions about research, as well as their exposure to the world of clinical research and their access to trials (i.e., access to technology, family physicians, local clinics). These factors are important to consider in order to understand the different realities faced by different groups and thereby to be able to prioritize diversity in trial samples, for example by addressing accessibility barriers for underrepresented groups and using culturally sensitive and appropriate language in communications.

Why is patient engagement important in clinical trials?

Patient engagement in clinical trials is important because it exerts effects on patient enrollment, retention, compliance with protocol, satisfaction, and, ultimately, trial quality and results. Patient engagement is closely intertwined with the concept of patient centricity - prioritizing the patient experience throughout the trial.

Solid patient engagement gives sponsors and CROs an opportunity to gain invaluable input and feedback from an important stakeholder who has traditionally been left out of the decision-making process – participants. Direct insights from the patient community can be used to improve the patient-centricity of trial operations in multiple ways, including:[³]

• Modifying design elements to increase the value and relevance of a clinical trial’s research objective(s) in the eyes of patients
• Coming up with new research questions and directions that directly address patient needs
• Adjusting aspects of protocols such as eligibility criteria, number of visits, etc. to encourage enrolment via more attractive, inclusive, and less-burdensome trials
• Developing better outreach messaging to reach under-represented communities, increasing sample diversity, awareness, and enrolment
• Developing logistic support, such as transportation for specific patient populations or financial compensation for participation

In recent years, the clinical research industry has seen a boom in patient engagement tools that focus on updating the outdated convention of research on human subjects to research with participants.[⁴] This concept can be thought of by an important buzzword currently making headlines in the clinical research industry: patient centricity. Patient engagement can inform patient-centric trial design, while patient-centric trials facilitate increased engagement - a positive feedback loop with benefits for sponsors, researchers, and patients alike.

What are some challenges in patient engagement?

There are several long-standing patient engagement challenges that the clinical research industry has been facing for years, which we discuss below in order to provide some context for the patient engagement strategies we elaborate upon in the next section:[⁵],[⁶],[⁷],[⁸]

Strict eligibility criteria

Eligibility criteria are important for fostering some degree of homogeneity in a sample, controlling for certain prognostic factors and covariates in order to strengthen conclusions. Nonetheless, clinical trials with overly restrictive eligibility criteria may unnecessarily limit the potential sampling pool. Not only do stricter inclusion and exclusion criteria mean that there are fewer eligible patients, but the screening process and enrollment overall will also become more time-consuming for the sponsor. Sponsors should aim to strike a balance between achieving a well-controlled sample and enhancing accessibility to diverse populations, which is more likely to result in a representative sample.

Complex and burdensome protocols

Additionally, if a trial design involves an overly complex intervention protocol, requires frequent in-person visits, or is so complex that it’s difficult for patients to even understand, patients could feel overburdened, overwhelmed, uninterested, or even become non-compliant, thus decreasing retention rates.

Lack of awareness and accessibility

Despite broad efforts to increase awareness about participation in clinical research, there is still a general lack of knowledge on the topic among the general population.[⁹] While social media has opened up vast new opportunities for outreach, it’s simultaneously becoming harder to grab the attention of the average person, who is estimated to be exposed to up to 10,000 ads per day. Meanwhile, stricter regulations have been put in place to limit online medical advertising and targeted marketing campaigns using personally sensitive information such as health data. Thus, raising awareness about clinical research - its purposes, benefits, and the possibility of participating - should be a priority for the industry.

Disparities in awareness of trials and accessibility to trials between different communities are also well-documented.[⁹] A 2020 HINTS survey indicated that the majority (62%) of respondents would go to their healthcare provider for information about trial participation, and research has demonstrated that people tend to seek physicians of their own race.[⁹],[¹⁰] Thus, onboarding healthcare practitioners from diverse communities as partners in education and diffusion is another strategy for boosting awareness and accessibility.

Many communities have limited access to healthcare, for a combination of socioeconomic and geographical reasons; such communities are less likely to be aware of the opportunity to participate in a trial. Clinical trials are often concentrated in certain areas, with sponsors and CROs often returning to the same high-performing sites (for understandable reasons), which tend to draw upon the same patient databases.

Fears, uncertainties, and doubts revolving around clinical research

Fear has been cited as one of the strongest hindrances to participation in clinical research studies, and is thus an important emotion to address when building patient engagement.[¹] Fear is related to multiple uncertainties implied in research participation, including unexpected side effects, adverse reactions, the possibility of receiving placebo rather than an active treatment, dealing with new or unknown healthcare providers, etc. Information and education are key tools for addressing this barrier:

“...while fear was identified as a critical factor deterring participation, there is evidence that this can be mitigated by research staff providing potential participants with adequate reassurance and detailed explanations of the procedural elements of the trial.”[¹]

Negative perceptions and misinformation

Further, there are common misperceptions and misinformation circulating, which may be especially relevant among minority groups or communities with a history of poor access to or experience with medical care. A legacy of medical distrust in the family or the community could further dampen prospective participants’ willingness to enroll in a study. While a significant percentage of people are not even aware of the possibility of taking part in a research study, others equate participating in a clinical trial to becoming human guinea pigs, which is related to perceptions along the lines of “the researchers don’t care about us.” Others may feel that “clinical trials are only for privileged white people.”

In many cases, these perceptions reflect deficiencies and inequalities in public health education and healthcare in many parts of the world. As a whole, the clinical research industry not only has a vested interest in, but is also well-positioned to rectify these misconceptions and help people feel safe and valued in their decision to participate in research.

4 Considerations for drastically improving patient engagement in clinical trials

Here, we’ve combined the considerations outlined above to synthesize 4 practical and actionable tips for designing effective patient engagement strategies in clinical trials.

These considerations can be drawn upon to develop a patient engagement strategy that is tailored to the needs of the trial and the sponsoring organization.

1. Involve patients as consultants and stakeholders: Patient-centric trials

One of the most successful methods for improving patient engagement is to get patients involved early on - in trial design - to develop patient-centric trials.

Who better to provide insight into the question “what makes a trial attractive and satisfying for patients?” than patients themselves? With direct patient input, sponsors and CROs can design trials that are aimed at addressing a real patient need, fill gaps in treatment options, and which create a smooth and satisfactory experience for patients. Patients who have gone through other trials will have valuable, first-hand insights into what factors might improve or hinder patient recruitment, retention, compliance, engagement, and communication.

A practical strategy for further engaging patients in clinical trials is connecting with patient advocacy groups and highly-informed patients. By involving such individuals as a sort of consultant, researchers can get a better understanding of their target participants’ concerns, desires, and lifestyles, and will be better equipped to address the barriers holding them back from participating. All this input can help in the design of better trials that support patients from beginning to end.

Patients and patient groups should be consulted carefully; it is important to understand the personal/group profile in order to have proper context for the insights they share. There will be instances where more structured, global insights from a patient advocacy group would be more helpful, and other times, patients with less knowledge about their condition or with only direct individual experience might be sought out to obtain more specific, personal insights. Both types of input can be valuable.

Broadly speaking, patient consultants could be classified into three general types: patients with personal experience, who can provide feedback on specific aspects of a trial and how it affected their lives; patient advocates, who know more about their patient community and can give anecdotal advice from their own experiences and those of fellow patients; and expert patients, who are aware of broader problems in healthcare and the issues affecting various patient communities.[¹¹]

2. Improve accessibility to trials and diversity in trial participation

It is important for a trial to be accessible to diverse groups, while still respecting the necessity of defining eligibility criteria to protect patients and control for prognostic factors to some extent. The following barriers to accessibility are common reasons for participants either not being aware of the trial at all, or not participating due to an inability or unwillingness (or both):

• Geographical factors - lack of local clinics or facilities where they can learn about trials, long travel (and high costs) required to reach trial sites, poor public transportation infrastructure, etc.
• Financial constraints - unable to take time off work, pay for childcare during study visits, travel costs, other out-of-pocket expenses related to trial participation
• Lack of education - misinformation, misperceptions, and lack of awareness of clinical research
• Healthcare disparities - low availability of physicians and healthcare practitioners may result in poor access to (or poor quality) healthcare, reducing exposure to trial opportunities as well as damaging trust in healthcare and pharmaceutical industries

Moreover, diversity in clinical trials has become a major issue in research, as the ethnic diversity of the general population is not being reflected in trial populations.

Increasing diversity improves the validity and generalizability of trial results, addresses inequalities in access to research, helps eradicate the stigma associated with medical research among underexposed communities to increase their engagement.

Some effective methods for increasing accessibility and diversity in clinical trials include:

• Modifying inclusion and exclusion criteria to allow diverse patients to qualify
• Decentralizing trials to reduce travel, allowing patients to visit local treatment centers or have home visits, using digital solutions like eCOA, ePRO, and eConsent
• Raising awareness and educating the public about clinical research in general
• Engaging with minority groups and under-represented communities, and having conversations about clinical trials
• Working with patient ambassadors - those who have had a positive experience are ideally positioned to improve sentiment in their communities
• Collaborating with physicians of different ethnicities to improve outreach into those communities
• Increasing diversity among clinical researchers and trial staff to better align with the target population - also making sure that site staff speak the languages your participants speak
• Investing in long-term targeted outreach

3. Be mindful of health literacy and communicate effectively

Health literacy refers to basic medical knowledge, as well as the ability to read and comprehend medical terminology and medical information, such as charts and diagrams, and to make informed inferences and decisions related to health.[¹⁵]

It is empowering for patients to be able to fully comprehend clinical trial documentation that explains the objective and protocol of a clinical trial. Furthermore, properly informed patients will be confident enough to ask questions, voice their concerns, and appropriately weigh the risk and benefits of participating, thus allowing trial staff to have constructive discussions that can improve enrolment and retention. Rather than publishing difficult materials and using high-level medical terminology, or repeatedly having lengthy discussions to clarify topics wherein participants might feel lost or overwhelmed, it is best practice to use clear and simple language. Consider that 88% of American adults are considered to have limited health literacy.[¹⁶],[¹⁷]

Informed patients will also be best equipped to provide relevant and valuable feedback. It’s in sponsors’ and CROs’ best interests to invest in improving health literacy through a multifaceted approach - working to educate the public in general, but prioritizing clear communication in the meantime so trial patients can fully understand the information presented to them. Specific approaches include:

• Creating content and study materials with direct, clear, simplified, easy-to-understand language
• Minimizing medical jargon and using layman terminology, in both written and verbal communications
• Repeating key information and asking questions at regular intervals (for example, “can you summarize what I just explained?”) to confirm comprehension
• Designing infographics, diagrams, and pictures to convey data and concepts visually
• Developing interactive materials such as video presentations, surveys, etc., to use in consent forms and promotional materials
• Integrating intuitive digital solutions that fit into patients’ lives and routines to share information and reminders for follow-up (mobile alerts, text reminders, periodic email newsletters, etc.)
• Sharing ongoing results with participants and showing appreciation

4. Raising awareness by building strong connections

Continuous efforts to raise awareness and foster connections within the community can help improve and sustain trial participation, especially among underrepresented and underserved groups. Many patients are willing to participate in a trial but are unsure how to get involved, but there is still a large percentage who are not even aware of the possibility.[⁹]

A few key strategies for raising awareness include:

• Sharing trial information with healthcare providers in the local area so they can bring it up with their patients
• Sharing trial information with local media outlets to improve visibility
• Publishing results of trials to improve transparency
• Sharing anecdotal experiences/testimonies of satisfied patients
• Establishing a presence as a trusted source of health information, either in the local community, online, or both
• Engaging with patient advocacy groups online and at local events

Raising awareness requires a joint commitment throughout the clinical research industry, involving clinical researchers, sponsors, healthcare professionals, and even patients.

Conclusion

Sustained patient engagement in clinical trials will be a natural side effect of true patient centricity. But there is work to be done to reach that point. Collaborative efforts throughout the industry are needed to improve awareness and address the issues of accessibility and diversity in trial participation, leading to samples that better represent the broader population, and thus results and outcomes that capture these individual differences and are more generalizable. Through efforts to increasingly engage minorities and underserved populations, long-term relationships and connections can be built that will improve trial diversity as well as perceptions about clinical research.

With a solid understanding of the challenges currently faced, and sufficient forethought and planning, sponsors can make clinical trials more attractive and engaging for patients by adopting the strategies we have described in this article. Beyond involving patients as stakeholders in the design of patient-centric trials, efforts need to continue throughout the clinical trial to ensure a positive patient experience, optimizing patient retention and satisfaction by being attentive, compassionate, and creating quality touchpoints in every interaction.