Ingrid Oakley-Girvan, PhD

Caregivers are essential partners in health care. Due to their direct, ongoing engagement with patients’ care, caregivers can often provide early insight into “simmering” symptoms the patient may be experiencing, as well as identify and report physical function when patients are at home, instead of waiting until they have a clinic visit. These observations and reports help clinicians and clinical investigators improve the view of their patients’ experiences and might even be predictive of adverse events.

While the full extent of caregivers’ impact on clinical trials is still being studied, both preliminary studies and anecdotal evidence point to some likely truths. First, caregivers play a significant, demonstrable role in the success of clinical trials, as they often facilitate visits, medication adherence, and help patients maintain overall wellness at home. Second, their impact on trial success can be further strengthened if sponsors design trials, when appropriate, to embrace the caregiver. Decentralized clinical trial (DCT) capabilities that empower patients and caregivers to participate from the comfort of home and lower participation burdens may result in more than an incremental change.

Caregivers play critical role in clinical studies

“Caregivers can make or break participation in a clinical trial,” says Karen Utley, whose 15-year-old daughter, Samantha, has CDKL5 deficiency disorder, a rare neurodevelopmental condition caused by pathogenic variants in the CDKL5 gene. In addition to serving as president of rare disease non-profit International Foundation for CDKL5 Research, Utley is her daughter’s primary caregiver—a 24/7 responsibility she has fulfilled since Samantha began having seizures at 10 weeks old.

Samantha, now 15, is a clinical trial success story. Since starting on the investigational therapy about two years ago, her seizures have dramatically reduced, and she is eating most of her meals orally for the first time in more than eight years. But while the investigative trial therapies themselves undoubtedly helped Samantha’s condition, none of these remarkable improvements would have been possible without the careful dedication of her caregivers.

“I am so grateful for the opportunity that trials have provided to my daughter, but she could not have participated alone. Trial participation can be completely dependent on a caregiver,” explains Utley.

In her experience, the role of the caregiver is twofold. The first role is logistical, such as getting the patients to their clinic visits and keeping everything organized. Caregivers often encourage patients to participate in trials in the first place and can increase the likelihood that patients will stay engaged even when feeling the effects of their illness.

“In order to participate in a brick-and-mortar trial, every three months (more frequently early on) we drove one hour to the airport and then flew from Houston to Denver followed by at least one night in a hotel room and at least five hours in the hospital where the trial was being conducted,” says Utley. “Then COVID forced remote participation, which for us included telehealth site visits and ECGs and blood draws locally. This dramatically reduced the burden on me as her caregiver, and without my involvement Samantha would not have experienced such improved quality of life.”

The second role is observational, through catching warning signs that doctors and even patients may not see or report themselves. Both these roles are particularly essential with patients like Samantha, but also with elderly populations and others whose communication, mental capacity, and mobility may be impacted by their disease.

Research is actively underway to compare how caregiver reports predict patient outcomes versus similar reports by patients themselves. Early evidence suggests that Samantha’s story is not unique. Patient-reported outcomes (PROs) can increase the patient’s quality of life, decrease emergency room visits and hospitalizations, and even increase survival.

 Caregivers can also provide information and early warnings of declining patient health.

The special role caregivers play can help retain patients in trials as well. The current drop-out rate is a disheartening 30%,

 slowing timelines and costing at least $19,300 per lost patient (the average cost to enroll a new patient in a Phase II trial).

 Ultimately, low patient retention delays treatments to patients and increases the cost of approved drugs, with consumers bearing the greatest burden.

“Any time you are in a position to care for a chronically ill person, that caregiver will be a huge part in whether that patient continues to participate,” says Utley.

While anecdotal evidence strongly supports the notion that caregivers provide essential insights about their patients, formal research is necessary. The digital science team at Medable recently set out to assess whether caregiver reporting is predictive of specific clinical outcomes.

In this study, more than 50 adult patients with solid tumors that were on active intravenous therapies and their informal caregivers were recruited from Kaiser Permanente Northern California cancer clinics. Using a mobile app called TOGETHERCareTM, caregivers completed weekly surveys for four weeks, using NIH-Patient-Reported Outcomes Measurement Information Systems (PROMIS) questions to report patients’ physical function and PRO-Common Terminology Criteria for Adverse Events (CTCAE) to report patients’ symptoms.

Patients’ adverse clinical outcomes, such as emergency department visits or hospitalizations, grade three and four adverse events, and treatment delays (up to one month following the four-week study period), as well as mortality and hospice referrals up to six months following the study period were evaluated.

The results? Caregiver-reported PRO-CTCAE predicted hospitalizations and mortality, and caregiver-reported PROMIS scores predicted hospice referrals. This suggests that caregiver reporting of patients’ symptoms and physical function could help provide early predictions of adverse patient outcomes. A DCT tool, such as TOGETHERCare, could help address symptoms earlier, thus improving patients’ quality of life and, ultimately, reduce trial dropout.

Empowering caregivers through decentralized trial design

If a clinical trial depends on the logistical and observational capabilities of caregivers, their success can be further bolstered by embracing DCT capabilities. “The more you support that caregiver, the more success you are going to have across the board,” says Utley.

From the logistics perspective, DCTs can dramatically reduce the burden on caregivers and patients, thereby increasing patient retention. For Utley and her daughter, travel was a significant factor. “Nothing would stop me from participating unless travel was too difficult for Samantha to handle,” says Utley, adding that participants may not see enough benefit to trial participation if travel is difficult for them. She also noted that their trial reimbursed her for travel and food costs, but not for work missed. All these challenges could be eased if trial designers made every effort to provide for remote reporting, observation, and visits wherever possible.

From the observational perspective, DCT technologies enable caregivers to report patient status in real time, rather than waiting for the next visit to the clinic. In a survey of 38 oncologists, every physician stated that they routinely rely on caregiver reports to evaluate patient symptoms and physical function/performance status with patients who have caregivers. And, in the case of a discrepancy, more stated that they relied on the caregiver’s report (45%) than on the patient’s report (8%).

 These real-time reports can help the clinic respond to symptoms before they escalate or result in trial dropout.

Wearable sensors and mobile apps can assist doctors, patients, and caregivers. By combining low-burden, home-based, remote digital measurements with patient- and observer-reported outcomes, not only can more patients access trials but also care can potentially be improved for patients in studies.

In the previously noted study of oncology patients and caregivers testing the usability of mobile apps, more than two-thirds of both groups felt that the apps studied would encourage patients to take better care of themselves, and more than half of the respondents in both groups thought that the app would improve their emotional well-being. In addition, almost 70% of caregivers thought the app would make them more aware of their loved one’s cancer symptoms and side effects.

 Finally, many oncologists6 prefer to receive critical values and data prior to a patient visit—which can be provided through the mobile app, showcasing the synergy between remote reporting and clinical use of such data.

Ease of use is crucial for ensuring patients and caregivers engage with mobile apps. Utley emphasizes the importance of supporting use for all caregivers; while there is usually a lead caregiver that provides a consistent perspective, that caregiver could get pulled away at any time due to illness or other factors. Therefore, all backup caregivers should also be empowered to report patient symptoms, perhaps by providing multiple logins to the mobile app to ensure ongoing diary keeping.

“Whoever is designing trials needs to make sure that the design is favorable,” says Utley. “Get input from the patient and the caregivers to make sure it is easy for them to support—or they will drop out.”

When they are properly supported with thoughtful tools and technology, caregivers can have a tremendous impact on patient participation and success in clinical trials. By removing some of the patient’s burden, caregivers improve the trial experience and may help patients remain in a trial through its duration. In contrast, when caregivers become weary, they can discourage participants from staying in a trial, or even ask them to drop out because participation consumes so much time and energy.

Trial sponsors should take this to heart. Providing caregivers with every opportunity to be actively involved might just play a make-it-or-break-it role in the development of successful new therapies. Trial sponsors should do all they can to support these essential stakeholders, thereby preventing trial attrition, saving money, speeding a therapy’s path to market, and driving better health outcomes for patients.

, PhD, SVP of Research and Strategy, Medable

National Library of Medicine, National Center for Biotechnology Information, “Family caregivers’ support their patient’s decision to participate in phase I clinical trial: Weighing the pros and cons,” by Naomi Kogan, Michelle Tolley, and Robin Cohen (April 23, 2022). 

https://pubmed.ncbi.nlm.nih.gov/35460308/

National Library of Medicine, National Center for Biotechnology Information, “Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment,” by Ethan Basch , Allison M Deal, Amylou C Dueck, Howard I Scher, Mark G Kris, Clifford Hudis5, Deborah Schrag (July 11, 2017). 

https://pubmed.ncbi.nlm.nih.gov/28586821/

, “Considerations for improving patient recruitment into clinical trials,” a white paper (accessed on July 6, 2022). 

https://www.clinicalleader.com/doc/considerations-for-improving-patient-0001

Praxis, “BLOG: The real cost of clinical trials” by Chelsea Roth (May 9, 2019). 

https://www.gopraxis.com/news/the-real-cost-of-clinical-trials/

 “Cancer Patient Symptom and Physical Function Reporting by Caregivers as Predictors of Adverse Clinical Outcomes,” by Elad Neeman, Reem Yunis, Ai Kubo, Sara Aghaee, Jennifer Shieh, Tess Veuthey, Stephanie Fonda, Raymond Liu, and Ingrid Oakley-Girvan (September 21, 2021) and presented at 2021 ASCO Quality Care Symposium. 

https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.12026

IBID. Elad Neeman, Ai Kubo, Elaine Kurtovich, Sara Aghaee, Maya Ramsey, Reem Yunis, Tatjana Kolevska, Raymond Liu, Ingrid Oakley-Girvan, “Mobile app and wearable sensor-based patient and caregiver physical function and reported outcomes: A survey on oncologists’ current practices and preferences on data delivery.” See full resource here. 

https://meetings.asco.org/abstracts-presentations/201813

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