Patient Insights & Current Vs. Next-Gen Patient Engagement

By Enrico Mastroianni, Anna Birna Almarsdóttir, and Janine Marie Traulsen

The FDA and the European Medicine Agency (EMA) have paid increasingly more attention to and prioritized patient engagement in their agendas; at the same time, the pharmaceutical industry has shown commitment to involving patients in the development of medicines and services. Some pharmaceutical companies have even established their own models for including patient perspectives in pharmaceutical value chains.  Guidelines have been proposed by bodies such as the European Patients’ Academy on Therapeutic Innovation (EUPATI), TransCelerate, and the EMA and the FDA. However, these guidelines lack theoretical development and empirical guidance. Furthermore, literature on the topic is limited and sometimes contradictory.  Various sources have proposed ways to engage patients, but guidance is lacking on how to do it effectively and in a meaningful way. The result is often that patient engagement turns into an ethical token of limited value, and the risk is that industry decisions are made based on flawed insights.  This article presents a critique of some of the existing guidelines for patient engagement, with particular focus on how they enter the research field lacking the rigor of empirical research standards. Finally, it concludes with recommendations for patient engagement within boundaries that would not overstep onto research, but that instead complement it with diverse forms of interaction with patients.

The Flaws Of Current Patient Engagement Guidelines

For many years, there has been confusion about exactly what role patients can and should play as collaborators in health research and policy. An editorial in the BMJ attributes this confusion to what the authors refer to as “an unhelpful diversity of terms.”¹

In 2018, Chudyk et al. recognized inconsistent ways of conceiving (or conducting) patient engagement.² In 2020, the ISPOR Patient-Centered Special Interest Group put forth a definition of patient engagement in research by synthesizing a comprehensive sample of literature on the topic:

The active, meaningful, and collaborative interaction between patients and researchers across all stages of the research process, where research decision making is guided by patients’ contributions as partners, recognizing their specific experiences, values, and expertise.³

This definition clearly refers to researchers and research, delimiting an area of engagement close to (or overlapping with) that of research. Previously, Domecq et al. had questioned whether engagement could be a form of insight generation along with empirical methods, arguing that research dedicated to identifying the best methods to achieve engagement is lacking and clearly needed.⁴ To find a solution on how to understand patient engagement, Esmail et al. proposed a way to look at it that differed from more traditional forms of research, respectively referring to “research with patients” and “research on patients,” where, simply put, the latter is the traditional research approach in which patients are the sample of the study (the subjects).⁵

As pointed out in 2018 by Liabo et al.,¹ the confusion has continued, also due to the diversity in the terms (“engagement” in North America, “participation” in The Netherlands, and finally the distinction between “engagement,” “involvement,” and “participation” in the U.K.) (ibid.). They suggest, in line with Esmail et al., that patients are sometimes in a role as data providers (participants in research) and in other cases as partners, with views and feedback on the research design. Confusion apart, we argue that these two roles should be clearly distinguished to ensure that patient engagement is never seen as a substitute for research and that research is never seen as a substitute for engagement.

Increasingly, it has been pointed out that defining who should represent the patient voice in patient engagement is a complex task. The representatives most often engaged are called patient experts or patient advisors. A document on patient engagement in the Design and Conduct of Medical Device Clinical Investigations, released by the FDA (accompanying a statement from September 2019), defines “patient advisors” as:

Individuals who have experience living with a disease or condition and can serve in an advisory or consultative capacity to improve clinical investigation design and conduct, but who are not study/research participants themselves.⁶

In a more recent and updated version of the above document (January 2022), it reads:

We encourage sponsors to be clear in their planning process about which activities are part of the study plan (i.e., for study/research participants) versus those that are non-research patient engagement efforts (i.e., for patient advisors) that may improve the design and conduct of the clinical study. … We encourage sponsors to consider using existing educational materials and/or partner with organizations that provide training for patient advisors to help them most effectively contribute.⁷

It is especially the last sentence that demonstrates the active role of the patient expert as contributor, as opposed to a more passive role of the research subject as data provider. Regarding how the active contribution of the former may occur, the document reads:

For example, a clinical study being designed to evaluate the performance of a mammography device might enlist women (regardless of whether they have a medical diagnosis) to be patient advisors.⁷

This example highlights the complexity of defining who should contribute patient insights. It also exposes one of the main problems with patient engagement regarding the lack of rigor in methodology and theoretical framework. The vagueness with which it defines “representativeness” is clear proof in this case.

According to Liabo et al. (2018):

Patients who take on the role of research partners also express views and identify priorities, but these contributions are not analyzed as data. … To resolve ongoing confusion, we must make a clear distinction between patients as data providers and patients as active partners.¹

It is obvious that patient engagement exists in a gray area. As shown above, some of the available sources for practical guidance have often proven to be unclear and do not harmonize with each other. 

In most cases, they provide mere lists of qualitative research methods with no reference to their theoretical and methodological origins. For example, in the Patient Engagement Overview some documents (e.g., on Patient Focused Drug Development, PFDD) refer to forms of qualitative research (focus groups, individual interviews, structured brainstorming, and sometimes mixed methods, although the documents do not always use these terms).  TransCelerate provides an advanced and comprehensive toolkit for patient engagement including instructions on how to set up focus groups and interviews, prepare discussion guides for interviews, and so on.⁸ The content of these is clearly inspired by qualitative research yet lacks academic rigor when compared to research method handbooks.⁹ For example, there is very limited theoretical reference in the Patient Protocol Engagement Toolkit, making it unclear whether the survey questions are based on indicators and how the data can be used after collection. A naïve application of research methods, derived from entrusting nonprofessional researchers with such tools, can raise questions of validity and reliability. In addition, if the results of such applications are taken as “insights,” the risk is that they may be flawed, invalid, and unreliable, and, hence, lead to poor decisions in development.

Finally, the Suggested Working Practice Checklist  of PARADIGM¹⁰ provides guidance on population representativeness, geographical diversity, etc. This is just one more example of guidance developed along the lines of empirical forms of research (on patients). However, even in this case, we find the complexity of empirical research is scarcely captured in these checklists and guidelines, consequently risking flawed results. 

The cases above highlight two problems:

1) The guidelines are not as comprehensive as social research handbooks and, in fact, pay little attention to data quality, with the risk of guiding the reader toward flawed research.  We discussed this point above.

2) The guidelines do not teach any new valuable skills to teams familiar with empirical methods (many pharmaceutical companies have well-established research teams) and miss the chance to train on truly new forms of interactions with patients.

Next-Generation Patient Engagement

Continuing to demand more patient engagement, even as it gets shaped and more clearly defined, may lead to two benefits that we have observed in industry:

a) an increase in the amount of research on patients, because a demand to interact with patients often encourages stakeholders to gather patients´ insights more often throughout the value chain; and

b) a diversified portfolio of activities that allow patients´ voices into the company’s research (going beyond research on patients). 

The latter is the riskiest but also potentially the most value-adding, and it requires disclaimers around what each form of activity can do, especially concerning insights generation and data.

The only activities able to generate legitimate patient insights are those where the methods can withstand the scrutiny of empirical criteria such as validity and reliability⁹ – in other words, activities that can generate knowledge, based on empirical standards.

An important clarification concerns the distinction between clinical research and social science research. In an attempt to go beyond clinical research and the “hard” data around the effectiveness and clinical impact of healthcare solutions and medications, the guidelines discussed above have focused on gathering insights on patients´ lived experiences, preferences, behaviors, etc. These qualitative insights, however, just like the clinical insights, must strictly follow the empirical standards, too: Social research methods are necessary to gather valid and reliable qualitative insights. For this reason, it is pivotal to distinguish between interactions with patients aimed at generating insights of objective and descriptive nature, and interactions meant to engage patients for prescriptive and co-creative collaborations. While all of them entail engaging patients, the terms in which the patients are engaged can be research-based or not, depending on the intended outcomes.

The pharmaceutical industry should not make the mistake of seeing one patient engagement activity as “more valuable” than the other, nor of putting research and engagement on two different levels of priority. Quite the opposite, it should embrace the diversity of interactions with patients and be aware of the value each can provide. It should leave the generation of insights and knowledge to empirical researchers and, at the same time, enrich the pool of patient interactions with other engagement opportunities, making the most of each.

At this point the opportunity for pharma is quite extraordinary. Based on your own models for the integration of new forms of interactions with patients, ranging from research on patients to partnerships, pharmaceutical companies could reflect on their own case studies and in this way pioneer a more operational definition of patient engagement, one that goes beyond the more generic one provided by the ISPOR group.³ A definition is needed that clarifies the benefits gained by each activity type, which could help FDA and EMA further improve guidance by perfecting the theoretical framework that clearly is missing today. The example from the IMI project, Hypo-RESOLVE, shows how a series of interviews with the researchers behind the project, hosted and moderated by the Patient Advisory Committee, could generate a dialogue between the two parts and shape agendas, negotiate priorities, and highlight possible gaps between the lived experience of patients and the understanding of hypoglycemia by researchers and practitioners, without the intention to treat all of this as insights or expert input.

Quoting again Liabo et al. (2018), “providers of data and active partners are both crucial to health research, and conflating the two is counterproductive to ethical, valid and patient focused research.”¹

We argue that the first step is to maintain clear boundaries between “research” and “engagement,” reflecting on whether (and where) these two overlap or are separate, and that the standards they are held up to are transparent, but not necessarily the same. 

The second step is to operationalize the concept of patient engagement, i.e., defining the diverse forms of interactions with patients, the purpose of each of these, and the value to be derived from them, at the same time using the rigor parallel to that of social science research.

In this way, patient engagement could open to a whole series of more inclusive activities that, together, would ensure an increasing presence of the patient voice throughout the value chains. If these steps are neglected, patient engagement will continue to be met with skepticism and even outright rejection from those who only accept “insights” under empirical conditions of validity and reliability.

References

1. Liabo K, Boddy K, Burchmore H, Cockcroft E, Britten N. Clarifying the roles of patients in research BMJ 2018; 361 :k1463 doi:10.1136/bmj.k1463
2. Chudyk A, Waldman C, Horrill T, Demczuk L, Shimmin C, Stoddard R et al. Models and frameworks of patient engagement in health services research: a scoping review protocol. Research Involvement and Engagement. 2018;4(1).
3. Harrington R, Hanna M, Oehrlein E, Camp R, Wheeler R, Cooblall C et al. Defining Patient Engagement in Research: Results of a Systematic Review and Analysis: Report of the ISPOR Patient-Centered Special Interest Group. Value in Health. 2020;23(6):677-688.
4. Domecq J, Prutsky G, Elraiyah T, Wang Z, Nabhan M, Shippee N et al. Patient engagement in research: a systematic review. BMC Health Services Research. 2014;14(1).
5. Esmail L, Moore E, Rein A. Evaluating patient and stakeholder engagement in research: moving from theory to practice. Journal of Comparative Effectiveness Research. 2015;4(2):133-145.  
6. Patient Engagement in Medical Device Clinical Investigations [Internet]. U.S. Food and Drug Administration. 2021 [cited 12 June 2021]. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-engagement-design-and-conduct-medical-device-clinical-investigations
7. Patient Engagement in the Design and Conduct of Medical Device Clinical Studies Guidance for Industry, Food and Drug Administration Staff, and Other Stakeholders. Document issued on January 26, 2022. [Internet] US Food and Drug Administration. 2022 [cited 23 July 2022]. Available from: https://www.fda.gov/media/130917/download
8. Patient Protocol Engagement Toolkit [Internet]. TransCelerate, 2021. [cited 05 August 2022]. Available from: www.transceleratebiopharmainc.com/ppet/set-up-patient-engagement
9. Bryman, A. (2016). Social Research Methods. (Fifth Edition)
10. IMI Innovative Medicines Initiative | PARADIGM | Patients active in research and dialogues for an improved generation of medicines: advancing meaningful patient engagement in the life cycle of medicines for better health outcomes [Internet]. IMI Innovative Medicines Initiative. 2021 [cited 12 June 2021]. Available from: https://www.imi.europa.eu/projects-results/project-factsheets/paradigm

Supplementary Reading

• Coquerel C, Kuruvilla S, Eichmann L. An Inside Look At Novo Nordisk's Disease Experience Expert Panel (DEEP) Model [Internet]. Clinicalleader.com. 2019 [cited 12 June 2021]. Available from: https://www.clinicalleader.com/doc/an-inside-look-at-novo-nordisk-s-disease-experience-expert-panel-deep-model-0001
• Brett J, Staniszewska S, Mockford C, Seers K, Herron-Marx S, Bayliss H. The PIRICOM study: a systematic review of the conceptualisation, measurement, impact and outcomes of patients and public involvement in health and social care research [Internet]. 2010 [cited 12 June 2021]. Available from: https://ukcrc.org/wp-content/uploads/2014/03/Piricom+Review+Final+2010.pdf  
• Manafo E, Petermann L, Mason-Lai P, Vandall-Walker V. Patient engagement in Canada: a scoping review of the ‘how’ and ‘what’ of patient engagement in health research. Health Research Policy and Systems. 2018;16(1).  
• Staniszewska S, Adebajo A, Barber R, Beresford P, Brady L, Brett J et al. Developing the evidence base of patient and public involvement in health and social care research: the case for measuring impact. International Journal of Consumer Studies. 2011;35(6):628-632.
• Minogue V, Girdlestone J. Building capacity for service user and carer involvement in research. International Journal of Health Care Quality Assurance. 2010;23(4):422-435.  
• Statement on FDA efforts to encourage patient engagement in medical device clinical investigations [Internet]. U.S. Food and Drug Administration. 2021 [cited 12 June 2021]. Available from: https://www.fda.gov/news-events/press-announcements/statement-fda-efforts-encourage-patient-engagement-medical-device-clinical-investigations
• Borup R, Traulsen J, Kaae S. Regulatory Capture in Pharmaceutical Policy Making: The Case of National Medicine Agencies Related to the EU Falsified Medicines Directive. Pharmaceutical Medicine. 2019;33(3):199-207. https://doi.org/10.1007/s40290-019-00277-0
• JDRF participates in new Research Project Hypo-RESOLVE to investigate Hypoglycaemia and its Impact in Diabetes [Internet]. JDRF. 2021 [cited 12 June 2021]. Available from: https://www.jdrf.org/press-releases/jdrf-participates-in-new-research-project-hypo-resolve-to-investigate-hypoglycaemia-and-its-impact-in-diabetes/
• Working with patients [Internet]. Novonordisk.com. 2021 [cited 12 June 2021]. Available from: https://www.novonordisk.com/partnering-and-open-innovation/working-with-patients.html
• Scibilia, R. “Lots about Lows”. Diabetogenic. 18 December 2020 [cited 25 September 2021]. Available from https://diabetogenic.blog/2020/12/18/lots-about-lows/
• Lau, S. R., & Traulsen, J. M. (2017). Are we ready to accept the challenge? Addressing the shortcomings of contemporary qualitative health research. Research in Social and Administrative Pharmacy, 13(2), 332–338. https://doi.org/10.1016/j.sapharm.2016.02.014
• Bradbury, H. (2015). The SAGE handbook of action research. (Third Edition).
• Hansen, M. B., Nørgaard, L. S., & Hallgreen, C. E. (2020). How and Why to Involve Patients in Drug Development: Perspectives from the Pharmaceutical Industry, Regulatory Authorities and Patient Organizations. Therapeutic Innovation & Regulatory Science, 54, 577-585. https://doi.org/10.1007/s43441-019-00090-6

About The Authors:

Enrico Mastroianni is user experience research lead at Novo Nordisk. He works with patients' insights and conducts empirical qualitative research for the development of physical and digital medical devices, including software as a medical device (SaMD). He holds an MA in cognition & communication from the University of Copenhagen and a BA in communication sciences from the University of Bologna. After working in communication, he joined the pharmaceutical industry as consultant in design psychology, and later joined Novo Nordisk, where he designed patient engagement activities and co-led the patient advisory committee of the IMI project Hypo-RESOLVE.

Anna Birna Almarsdóttir is professor of social and clinical pharmacy at the University of Copenhagen and head of the WHO Collaborating Centre for research and training in the patient perspective on medicines use. Her research interests include the patient perspective on medicines use and pharmaceutical policy analysis. She has studied children as medicine users as well as complex patients (who have many diseases). The latter focuses on how patients can tailor their medicines use with the help of clinical pharmacists collaborating with other health professionals in various settings. She continues to study new ways of gauging patient experiences with medicines.

Janine Marie Traulsen is an external lecturer, coordinating and teaching executive courses at Copenhagen Summer University in market access for pharmaceutical products, value-based healthcare, and digital health. She has a Ph.D. in sociology from The University of Lund, Sweden. She has worked as associate professor at the University of Copenhagen (1996–2016), where she taught and was advisor for undergraduate, master’s, and Ph.D. students. Her main areas of research include pharmaceutical policy, the pharmacy profession, the patient perspective, health technology assessment, and (more recently) digital health. She has authored/co-authored several books and more than 100 scientific articles.