Including Patients as Partners in Clinical and Outcomes Research



By John Watkins, PharmD, MPH, BCPS,
Managed Care Perspectives, LLC, Bothell, WA, USA

Patient centricity is a relatively new perspective. It’s easy to regard patients as objects to be treated or problems to be fixed, rather than as people with hopes, dreams, and unique life circumstances. Patient-centered healthcare is “respectful of and responsive to individual patient preferences, needs, and values in context of their own social worlds. Patient centeredness is created by engaging, informing, and actively listening to people with chronic conditions at every point of contact.”1 Organic inclusion of patient voices in research helps develop treatments that improve their lives in ways that matter most to them. It is good economics and good policy because the patient is the ultimate judge of value. To achieve patient centricity in research requires thought and effort. Patients and caregivers must work with researchers at every stage of the process.2,3


Patient-centric research processes
For results to be generalizable, researchers need a broad sample representing the heterogeneity of the patient population, but subgroups are often missed in recruiting due to logistic, financial, and/or sociocultural barriers to participation. Patients can help identify these barriers and suggest ways to improve recruitment from the overlooked groups. Patient-centered outcomes must relate to patients’ experiences, perspectives, needs, and priorities. They are the ones that patients think are meaningful to them, regardless of how the data are obtained. (References to “patients” in this article include caregivers where appropriate.)

Patient-centric research was defined by ISPOR’s Patient Engagement in Research Working Group as “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.”4 Patient-centric research identifies questions meaningful to patients, refines study designs based on their insights, and produces results that are useful in making patient-level decisions. According to research by Perfetto et al, “Patients might report that what is important to them are everyday life impacts—concepts that can be very different from the more typical clinical outcomes we often track.”5 A parent of a teenager with muscular dystrophy commented that her son was more interested in being able to IM a friend than in living longer.


"Organic inclusion of patient voices in research helps develop treatments that improve their lives in ways that matter most to them."


Participation should continue as study designs and endpoints are developed. When enrolling for the study, patients can help recruit subgroups. Where communities distrust research, patients can help understand the issues and locate trusted voices in the community to build trust.6 Patient-Centered Core Impact Sets help understand the needs of patients with chronic disease, creating disease-specific lists of the effects patients identify as most important to them to guide research that aligns with patient-informed value elements. The concept is currently being developed and has potential to help researchers, patients, and others in the future.7,8

During trials, patients should be involved in monitoring and adjusting study protocols. Patients can participate in safety surveillance, including data safety monitoring boards. At study completion, patients can take part in interpreting results and communicating with their communities. If people see why the trial matters, they will more likely volunteer for follow-up studies. Study patients can share their experiences and encourage others to follow the resulting treatment guidelines, improving outcomes.

The Patient-Centered Outcomes Research Institute (PCORI), an “independent, nonprofit research organization that seeks to empower patients and others with actionable information about their health and healthcare choices,” funds comparative effectiveness research to help patients and other stakeholders make better informed decisions. Its creation was an important step in focusing public attention on the patient voice. “What do we know about my condition and how to treat it? How do alternative treatments compare? What can I expect from each option?”

PCORI created PCORnet®, a national resource for patient-centered outcomes researchers. The organization is continually developing better ways to engage patients and amplify the effect of their voices.9 PCORI has published Methodology Standards to guide research that is meaningful to patients.10 Key points include:

  • Measure outcomes that people representing the population of interest notice and care about (RQ-6)
  • Engage people representing the population of interest and other relevant stakeholders in ways that are appropriate and necessary in a given research context (PC-1)
  • Identify, select, recruit, and retain study participants representative of the spectrum of the population of interest and ensure that data are collected thoroughly and systematically from all study participants (PC-2)
  • Use patient-reported outcomes when patients or people at risk of a condition are the best source of information for outcomes of interest (PC-3)
  • Support dissemination and implementation of study results (PC-4). [Results should be publicly available in language understandable and actionable to as many people as possible in the population of interest.]
  • Data-sampling plans should be designed to avoid selection bias (DR-1E)


Real-world evidence
Patient participation in large database studies (as research-team members, not observers) can improve the validity and usefulness of results.11 Machine learning algorithms may be influenced by subtle biases in the training data or historical trends, or unconscious biases of the programmers, and can amplify these biases.12 Patients can identify certain biases so that they can be corrected. Patients with lived experience anticipate barriers to applying results that researchers would miss, such as the impact of a time-consuming treatment protocol on a single parent navigating inflexible work and school schedules and meeting the logistic and emotional needs of patient and siblings. Patient input is required for economic models to reflect true value based on lived experience. The post-COVID remote work environment creates situations where model builders do not live in the environments their models represent. Consultation with patients can produce more realistic models.


Patients as full partners
In a patient-centric process, patients are partners. “I always felt the medical staff was working with me, not on me, giving me the power of decision,” one patient with cancer explained. “They’ve advocated very strongly at times for certain things, but I was making the decisions. It’s the patient’s life. It’s their body.”13 For patients to be heard, they must speak researchers’ language, understand their thought processes, and know their constraints. Not all patients need extensive technical training, but each patient group should have informed advocates. To facilitate learning, the National Health Council, an umbrella organization for patient advocacy groups, offers a variety of online resources that provide technical knowledge for patients.14 The National Organization for Rare Disorders also provides education focused on the needs of their constituency.15

Patients in minority communities need education, too. Educators must go into those communities. The PATIENTS Program is “an interdisciplinary research team of community partners and researchers housed at the University of Maryland School of Pharmacy that works to change the way we think about research by creating a path for health equity.” The program reaches patients where they are, caring about them, and showing them that they can be involved as an important part of the process.16


"Patient participation in large database studies (as research-team members, not observers) can improve the validity and usefulness of results."


Team members listen before they speak. “They actually care about what the patient wants. They actually ask the patients themselves, ‘What research would you like to see,’” says Gail Graham, Director of HIV Research at Mt. Lebanon Baptist Church in Baltimore. They help patients see “that they are the most important member of their treatment team. They’re part of the team working to save their life, to enhance their life, to prolong their life,” explains Cynthia Chauhan, a Patient Advisor. The PATIENTS Professors Academy offers a 5-week virtual training program for active participation.

The average advocate does not need more extensive technical training, but it is useful to have some “patient experts” who can converse at this level. The European Patients’ Academy on Therapeutic Innovation (EUPATI) trains experts “empowered to work effectively with the relevant authorities, healthcare professionals, and industry to influence the medicines development process for the benefit of patients.” Developed by patients with academic experts, the 1-year EUPATI Patient Expert Training Programme covers the lifecycle of pharmaceutical research and development and teaches patients how to contribute constructively at each stage. More than 250 EUPATI Fellows from Europe and elsewhere have completed this program. Over 70% hold leadership positions in a variety of patient organizations.17


Rare disease patient concerns
Rare disease patient advocates report that manufacturers listen to them more frequently than payers and health technology assessment (HTA) agencies.18 “Smaller biotechs seem to do better at this than Big Pharma, but there are still improvements to be made,” one advocate noted. “The focus for payers seems to be on what can get the job done the cheapest versus what’s best for the patient and caregiver. Decisions like this not only lead to wasteful spending, but the patient’s/caregiver’s needs still aren’t met.”


“You need to balance the needs of the patient for treatment with the need for experimentation.” Stanley Crooke, MD, PhD


Patients with degenerative disease often appear normal at birth. It may take several months before parents notice missed developmental milestones. A diagnostic odyssey usually follows. One parent wished for “a durable treatment given soon after birth to ameliorate the disease or make it more manageable so patients could walk longer versus spending a lifetime in a power wheelchair, which has a domino effect on overall health.” Her challenges include “balancing work and family responsibilities as my son ages and needs 24/7 assistance, need for respite care, paying for costs not covered by insurance, finding accessible and affordable housing, marital stress, and unexpected hospitalizations.”

Her son’s condition affects the whole family. “Sometimes the devil is in the ugly details. My son has lost most of his upper body function. He can no longer scratch an itch, which may seem unimportant, but imagine what it means to a 16-year-old boy who has mosquito bites and has to call out for someone to come and scratch them for him? When his friends are playing sports, he has to be careful to stay out of the way of an errant ball because he can’t lift his arms up to protect his face from getting hit. These are the heartbreaking realities I witness every day—the little things that become so big. My son hasn’t slept a full night since he lost ambulation and can no longer turn himself over at night for comfort. We haven’t slept a full night since then either. Any treatment effect should be viewed within the context of caregiver experience. Value assessments can be somewhat useful but miss a lot if they’re not sensitive enough to actual lived experience. Caregiver experience/impact, such as sleep quality, physical pain as a result of caregiving, and mental health is rarely fully captured by these tools.”

Payers’ decisions often don’t make sense to her. “Wheelchair seat elevation or other functions like headlights are constantly denied as ‘not medically necessary.’ As a caregiver, this tells me they don’t think a person in a wheelchair needs to elevate chair height to enjoy dinner at a restaurant or be more independent by being able to reach differing heights; nor do they need headlights to roll through a parking lot after dark so they don’t get backed into by a car. It’s so senseless and frustrating.” Caregivers would like to have more assistive medical technologies to maintain independence, but question whether payers will cover them. Required access modifications to homes and vehicles often are not covered. Patients experience “battles with the education system, battles getting medical staff to recognize parent expertise, divorce leaving one parent to bear the majority of caregiving, and loneliness.” Treatments that extend patient survival may leave aging parents worrying about who will care for the patient when they are unable.

The needs of atypical patients are often overlooked. According to Michelle Rice, a hemophilia advocate, the needs of her patient community are generally well understood and providers and payers are sympathetic, but “you can’t reach every payer or every administrative agency so there are some who have never truly “engaged” directly with a patient advocacy organization or a patient.”


“Consistently and systematically engaging patients across the lifecycle of medicine development creates value for patients, pharmaceutical companies, and society overall.” — Marc Boutin


“Hemophilia and related bleeding disorders affect all races, ethnicities, and genders,” Rice explains. Because hemophilia is generally considered a male disease, “women tend to be underrepresented in clinical trials. Historically, women were categorized as ‘symptomatic carriers’ rather than ‘hemophilia patients.’ There has been a recent push to bring in more women and people of color in clinical trials.” While there are more therapeutic options than for most rare diseases, Rice reminds us that “not all hemophilia patients bleed the same or respond the same to treatment.” At the top of her wish list would be a treatment “that provides sustainable, consistent levels of hemostasis, prevents spontaneous bleeding, and resolves injury-related bleeding without needing to re-dose.”

Patients with unique mutations are a special minority for whom targeted drug development is not commercially feasible. Stanley Crooke, MD, PhD, retired CEO of Ionis Pharmaceuticals, formed the nonprofit N-Lorem Foundation, which sequences the DNA of individual patients and synthesizes an antisense oligonucleotide to target the mutation. Crooke estimates a lifetime supply for one patient will cost around $700,000 as the steady-state price he thinks they can achieve. Here too, researchers need patient input. “These are patient lives,” he says, “so we try very hard to define the primary treatment goals that matter to the patient and secondary or exploratory goals and specific measures. You need to balance the needs of the patient for treatment with the need for experimentation.”19


Manufacturers can support partnership
Manufacturers are finding different ways to engage patients. Marc Boutin, Global Head of Patient Engagement at Novartis Pharmaceuticals, is driving change at his company, “making medicines with patients, not for them.”20 For Boutin—an attorney, former patient advocate, person living with a chronic disease, and cancer survivor—it’s personal. “Consistently and systematically engaging patients across the lifecycle of medicine development creates value for patients, pharmaceutical companies, and society overall.”

“When we co-create patient-relevant endpoints with the patient community, we identify and validate fit-for-purpose measures, core outcome assessments, and the need for patient preference studies—all of which informs our regulatory submission,” Boutin explains. “The resulting label defines our commercial strategy and informs our efforts to ensure that the right patients get access to life-altering medicines as quickly as possible.” Patient engagement helps Novartis reduce costs by avoiding products that won’t matter to patients, improving trial protocols, increasing enrollment, and reducing dropout rates. He believes this is “a true win/win…an investment in good decision making.”

Boutin lays out a model for others to follow. “Together with patients and associates, we developed a vision, strategy, and framework for ensuring patient input into key decisions across Novartis. Rather than create a separate patient engagement process, we embedded our work in existing processes like the target product profile, integrated evidence, clinical development, and one-impact planning. As the patient voice permeates every aspect of the company, it reinforces our collective and personal purposes.”

Medicine has traditionally been paternalistic. There is an asymmetry of scientific information that leads to unconscious bias that the professional knows what is best. When we listen to patients, we learn that there is an opposing asymmetry of information and understanding about their circumstances, desires, hopes, and dreams. Novartis has learned that “when you engage patients, you learn that how they feel, function, and survive are all important but weighted differently depending on their disease progression and personal goals. For example, some people living with schizophrenia do not want their treatments to stop their hallucinations—it’s part of their creativity.”

Novartis plans to implement “a new impact measurement framework designed to ensure systematic patient engagement, insight-driven decision making, and the generation of value for patients, healthcare systems, and Novartis.” Other manufacturers are developing similar programs. Patients will come to expect this level of engagement and will need the resources to learn the technical skills they need to be full participants in a relationship where each side has knowledge that the other doesn’t, each recognizes the value of what the other side knows, and they have a common language to communicate effectively with each other. Regulators are increasingly demanding patient experience data and HTA agencies are seeking evidence that demonstrates value to patients, Boutin observes.


Patient centricity and payers
Most payers have not had a patient-centric view, but as stewards of increasingly scarce healthcare dollars, they want to pay for what has the best value to patients. Payers listen to feedback from plan members, but they also need to hear from patient groups. However, most lack the resources in terms of expertise and budget to cover the costs. More awareness of the need and the emergence of virtual meeting technology is a game changer that allows patients and payers to communicate inexpensively.  

HTA agencies connect patients and payers. It is more efficient for them to dialogue with patients and share the results with the payer community. In 2016, the Institute for Clinical and Economic Review (ICER) began to include a patient section in their reports. Patients’ response to ICER’s work has been mixed, and they are the first to point out ICER’s shortcomings, but payers use ICER reports in formulary and coverage decisions. While few payers have time to read all the information ICER shares publicly, the reports’ summary of patient concerns should begin to expand payer awareness.

Reading the ICER reports may encourage payer pharmacists to reach out to patient advocates directly. Sickle cell disease was reviewed by ICER in 2020.21 This condition affects 1 in every 500 African American live births, but until 2019, there were no new treatment options. ICER quoted frustrated patients who encountered unsympathetic emergency department staff that didn’t believe them when they presented with acute pain in vaso-occlusive crises. Their stories caused Premera Blue Cross pharmacists to revise the opioid pain medication coverage policy to give patients with sickle cell disease the same exemption as cancer patients. Premera simply had no idea this problem existed. Once they learned about it, they found a simple way to help.22 Premera developed an ongoing relationship with the Sick Cells patient advocacy group and later arranged for a virtual presentation to the Premera Pharmacy and Therapeutics Committee.

ICER again reviewed sickle cell disease in 2023, as 2 potentially curative gene therapies were pending US Food and Drug Administration approval, bringing new hope to patients with this devastating disease. Sick Cells continues to work with ICER and others “to improve value assessments for sickle cell disease through a transparent and collaborative approach, representation of patient and caregiver perspectives, high-quality databases that adequately account for the diversity of patients with sickle cell disease, and methods that support equity. Sick Cells works with patients, researchers, health economists, payers, and providers to find the right approach to measuring cost and value for sickle cell disease.”23

Patient input has helped HTA organizations recognize that lack of patient diversity in clinical studies affects the representativeness of the results and decreases their value. ICER recommends that a threshold be established for “adequate representation of racial and ethnic populations in clinical trials.” Deliberative processes should be used. HTA should promote a balance between population health and individual patient needs, so that limited resources are equitably distributed. Reviewers should note when clinical evidence does not adequately represent minorities.24 ICER ‘s topic selection criteria now include consideration of underlying inequities in the population of interest, favoring treatments that can potentially reduce those inequities. Early engagement with those communities is critical to success.

The Innovation and Value Initiative seeks to create “a US learning healthcare system supported by patient-centered health technology assessment and focused on high-quality, efficient, innovative, and equitable care for all people and communities.”25 Their work focuses on heterogeneity in patient populations.


"Patient input has helped HTA organizations recognize that lack of patient diversity in clinical studies affects the representativeness of the results and decreases their value."


Expanding possibilities with innovative technologies
Virtual meetings let researchers recruit a broader range of patients whose schedules don’t permit travel to study sites. Patients can interact more frequently and participate more fully in the research. Low-income patients with logistic challenges are more likely to participate if travel is minimized. “We deal with families who are getting care at the closest center, even if it’s not a specialty clinic, and have no way of taking time off work to commit to a trial. Some are struggling to keep their heads above water or have no accessible transportation,” an advocate from the Little Hercules Foundation commented. Remote rural patients far from study centers may benefit from virtual technology if they have adequate Internet speed and bandwidth.

Creative means of remote data gathering can reduce participant burden and enhance interpretation of outcomes. For example, video capture data transmitted with a smartphone lets researchers view in-home performance of patients with muscular dystrophy, augmenting less-nuanced clinical trial endpoints with observations that reflect what matters to patients, the subtle variations in that caregivers see every day. This could provide supplemental evidence for regulators and guide appropriate treatment.26 Regulators will need to change how they evaluate studies, validating new endpoints and reviewing new types of evidence. Payers must understand the methodology to evaluate such evidence when making formulary decisions.

Social media provides a way of gathering perspectives from informal conversations that patients might be reticent to share with investigators. Natural language processing will facilitate collecting and organizing this input. Machine learning algorithms can automatically detect adverse events in postings on public sites. This is particularly useful in pharmacovigilance because patients often don’t report side effects.27

Social media data can help researchers understand the subjective experience of a broader range of patients than beyond their trial population. Sentiment analysis assesses the ratio of positive and negative words in a post to infer the individual’s opinion about a treatment. Comments regarding switching treatments are also useful. Of course, social media has well-known biases and “echo chamber” effects. People tend to present idealized versions of themselves, and those that eschew social media use entirely will not be represented. Nevertheless, social media may add valuable insights. Ethical considerations around data extracted from public postings need to be carefully examined.

Properly incorporated in research processes, patients can help us return to viewing populations as collections of diverse human beings for whom we strive to extend life and improve its quality. Their voices remind us that research subjects are people with lives, rather than problems to be fixed through “druggable” targets. As we include them in the design and execution of studies and interpretation of the results, they will help us identify population heterogeneities that impact treatment choices, helping us deliver improved outcomes and reduce numbers needed to treat, improving the cost-effectiveness of those treatments. ISPOR’s mission is improving healthcare decisions. Patient voices can help us do that better.



1. National Health Council. Glossary of Patient Engagement Terms. Accessed November 16, 2023. https://nationalhealthcouncil.org/additional-resources/glossary-of-patient-engagement-terms/#ftnref1

2. Vanderhout S, Nicholls S, Monfaredi Z, et al. Facilitating and supporting the engagement of patients, families, and caregivers in research: the “Ottawa model” for patient engagement in research. Res Involv Engagem. 2022;8:25.

3. Desai PJ, Zott C, Gauthreaux N, et al. Trust & Patient-Centeredness Workgroup: An Introductory Handbook for Patient Engagement Throughout the Patient-Centered Clinical Decision Support Lifecycle. AHRQ. Accessed November 16, 2023. https://cdsic.ahrq.gov/sites/default/files/2023-10/TPC%20Pat%20Engage%20Handbook%20Final.pdf

4. Harrington RL, Hanna ML, Oehrlein EM, et al. Defining patient engagement in research: results of a systematic review and analysis. ISPOR Patient-Centered Special Interest Group. Value Health. 2020;23(6):677-688.

5. Perfetto EM, Oehrlein EM, Rosie-Love T, et al. Patient-centered core impact sets: what they are and why we need them. Patient. 2022;15:619-627.

6. The PATIENTS program, University of Maryland School of Pharmacy. Accessed November 16, 2023. https://www.pharmacy.umaryland.edu/programs/the-patients-program/

7. Perfetto EM, Rosie-Love T, Oehrlein EM, et al. A foundation for patient-centered core impact sets: key learnings from past and existing approaches. Patient. 2023;16:293-300.

8. dosReis S, Butler B, Caicedo J, et al. Stakeholder-engaged derivation of patient-informed value elements. Patient. 2020;13:611-621.

9. Patient-Centered Outcomes Research Institute. Accessed November 16, 2023. https://www.pcori.org/about/about-pcori.

10. PCORI Methodology Standards. Accessed November 16, 2023. https://www.pcori.org/research/about-our-research/research-methodology/pcori-methodology-standards#Formulating%20Research%20Questions

11. Oehrlein EM, Schoch S, Burcu M, et al. Developing patient-centered real-world evidence: emerging methods recommendations from a consensus process. Value Health. 2023;26(1):28-38.

12. Manyika J, Silberg J, Presten B. What do we do about the biases in AI? Harvard Business Review. Published October 25, 2019. Accessed November 16, 2023. https://hbr.org/2019/10/what-do-we-do-about-the-biases-in-ai

13. Watkins J. Understanding value in cancer care. Value & Outcomes Spotlight. July/August 2021. Accessed November 16, 2023. https://www.ispor.org/publications/journals/value-outcomes-spotlight/vos-archives/issue/view/the-benefits-and-challenges-of-aging-in-place/understanding-value-in-cancer-care

14. National Health Council. Accessed November 16, 2023. https://nationalhealthcouncil.org/education/

15. National Organization for Rare Disorders. Accessed November 16, 2023. https://rarediseases.org/

16. The PATIENTS Program. University of Maryland School of Pharmacy. Accessed November 18, 2023. https://www.pharmacy.umaryland.edu/programs/the-patients-program/

17. European Patients’ Academy on Therapeutic Innovation (EUPATI). Accessed November 16, 2023. https://learning.eupati.eu/

18. A small convenience sample of rare disease advocates was surveyed for this article. Patient advocate statements not otherwise attributed were made by respondents to this survey.

19. Crooke S. Comments at the St. Jude Children’s Research Hospital Pediatric Translational Neuroscience Initiative Workshop, Memphis, TN, November 2, 2023.

20. Boutin M. Patient Engagement and Access to Medicines. Novartis Pharmaceuticals Impact and Sustainability Update Q2 2023 for investors and analysts. Accessed November 17, 2023. https://www.novartis.com/sites/novartiscom/files/novartis-q2-2023-impact-and-sustainability-update.pdf

21. Bradt P, Synnott PG, Chapman R, et al. Crizanlizumab, Voxelotor, and L-Glutamine for Sickle Cell Disease: Effectiveness and Value. ICER Evidence Report Posted March 12, 2020. Accessed November 17, 2023. https://icer.org/wp-content/uploads/2021/02/ICER_SCD_Evidence-Report_031220-FOR-PUBLICATION.pdf

22. Lee M. Presented at AMCP Nexus, Denver, CO, October 2021.

23. Sick Cells. Value and Cost. Accessed November 17, 2023. https://sickcells.org/value-and-cost/

24. Institute for Clinical and Economic Review. Advancing Health Technology Assessment Methods that Support Health Equity. March 15, 2023. Accessed November 12, 2023. https://icer.org/wp-content/uploads/2022/07/ICER_Advancing-Health-Technology-Assessment-Methods-that-Support-Health-Equity_040523.pdf

25. Innovation and Value Initiative. Principles for Value Assessment in the US. Accessed November 12, 2023. https://thevalueinitiative.org/principles-for-value-assessment-in-the-us/

26. Leffler M. Presented at New England CEPAC (ICER) public meeting, Cambridge, MA. July 25, 2019. Accessed November 18, 2023. https://www.youtube.com/watch?v=SFI54OjjLZU

27. McDonald L, Malcolm B, Ramagopalan S, Syrad H. Real-world data and the patient perspective: the PROmise of social media? BMC Medicine. 2019;17:11. https://doi.org/10.1186/s12916-018-1247-8



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