In the realm of healthcare, there exists a group of unsung heroes whose influence extends far beyond the walls of hospitals and clinics. These everyday champions, known as caregivers, invest not only their time but also their hearts into the well-being of those they support. It is important to note that, even though the healthcare community has recognized the relevance of caregiver’s quality of life in the wider context of patient centric treatment approaches, there is almost no mention of considering the caregiver’s quality of life as a surrogate end point in clinical trials. Surrogate end points are not the main goal, but they help us see the progress in treatments. It is like tracking the footsteps to know where someone is going. So, the question is how the well-being of those who provide care becomes a poignant barometer of treatment success, transforming the way we measure healing and progress in clinical trials.
Here the focus is on informal caregivers (parent’s or close relatives) of patients who are heavily dependent on them to perform day-to-day activities independently.

 

Why recognize caregivers as essential stakeholders in the caregiving equation and how will assessing their quality-of-life lead to more holistic and effective healthcare strategies?

1. Communication Barrier

Very young kids or patients suffering from some form of cognitive impairment cannot self-report the treatment progress from their perspective.

Here instead of patient’s quality of life, caregiver’s quality of life can be chosen as a substitute.

2. Observing Subtle Changes

Caregivers notice subtle improvements that patients might miss.

Example: Improvement in Pruritic symptom (itching) that worsens at night in PFIC patients.[1]

Here caregiver’s hours of sleep can be used as a quantifiable outcome.

3. Long-term Perspective

Caregivers provide insights into the long-term trajectory of a patient’s health.

For example, in chronic and terminal illnesses requiring multiple and sporadic medical interactions.

4. Prioritizing Symptoms or Treatments

Caregivers can help prioritize symptoms or treatments to improve both patient and caregiver quality of life.

For example, preferring an orally administered drug over an IV infusion saving time, travel expense, hours missed in school in case of kids etc. [1]

5. Emotional and Social Impact

Taking care of a patient who is completely dependent on them takes a mental toll on the caregiver.

This not just decreases the quality of life of the caregiver, but also indirectly that of the patient they are caring for.

Due to the above-mentioned reasons, the healthcare community has recognized caregiver’s quality of life as a significant criterion in determining the progress of a treatment in general.

Yet, in the arena of clinical trials and treatment evaluation, their role has often been overlooked when the successful participation of the patient in a clinical trial requires all the support from caregiver from screening and informed consent through to its conclusion.[5] In the current scenario there are many instances where caregivers played an important role in decision making and treatment progress tracking. For example, Observer Reported Outcome Assessment (OROA), one among the four clinical outcome assessments played a vital role in the approval of Odevixibat for pruritus in PFIC patients. Here it is important to note that caregiver’s quality of life wasn’t considered as a surrogate end point to track the treatment progress, but caregiver’s observations regarding the patient’s quality of life was used to make decisions.  It shows that there remains an opportunity to enhance the holistic evaluation of treatment progress by formally considering caregiver quality of life alongside patient outcomes in clinical trials and regulatory decision-making.[1]

Methods used to calculate caregiver’s quality of life

There have been extensive research going on from decades which has prompted a positive shift, with caregiver’s quality of life being increasingly incorporated into healthcare decisions. As a result, there are various tools or methods available currently to measure caregiver’s quality of life. The common tools or methods used to measure quality of life of caregiver in a clinical trial is given below:

  • Zarit Burden Interview (ZBI) [3]
  • Caregiver Strain Index Plus Positives (CSI+) [4][2]
  • Short Form Health Survey (SF-36/SF-12): General HRQoL measuring questionnaire.[7]
  • EuroQol-5D (EQ-5D): General HRQoL measurement questionnaire.[8]
  • Quality of Life in Caregivers (QoL-C) [2]
  • The Burden Scale for Family Caregivers—Short Version (BSFC-s) [2]

The interesting fact is that these are tools designed to recognize:

  1. Caregivers who need help. [2]
  2. To identify the specific part of caregiving that is affecting the caregiver’s quality of life negatively. [2]
  3. As tools that help caregivers to initiate conversations with a professional in case, they don’t come forward themselves due to fear of stigma, lack of resources, cultural taboo etc. [2]

The purpose of all these tools is to provide valuable ancillary information about the quality of life and well-being of caregivers to help guide supportive care and interventions for caregivers involved in the trial. The caregiver’s QoL is not considered as a surrogate endpoint in clinical trials even when it is very evident how much insights and treatment progression information can be obtained from it. While NYHA provides a clinical assessment by a healthcare provider and KCCQ helps to measure QoL of patient through patient reported information, there is no representation for caregivers in this realm. There is a pressing need to include caregiver’s quality of life as one of the surrogate outcomes of the trial because it can give a holistic picture to measure the success of a clinical trial.

For example, a study focusing on patients suffering from Hunter syndrome, who are often treated with systemic enzymes aimed to investigate the treatment progress after the intrathecal administration of the enzyme by assessing the IQ or cognitive ability as endpoints. However, these endpoints were difficult to assess, but the caregivers noticed that the patients were more independent in using the restroom. This has a huge impact on the quality of life of the caregiver, and hence it will be useful to monitor the stress-index, sleep hours, days missed at work, support hours needed by the patient etc. to arrive at the quality of life of the caregiver. This will in turn help capture the treatment progress that couldn’t be captured otherwise. [1]

Problem of incorporating carer’s quality of life as a surrogate endpoint in clinical trials

  • Surrogate endpoints in clinical trials are usually selected based on their established scientific correlation with the clinical outcome of interest. It is difficult to correlate scientifically caregiver’s quality of life and the treatment progress.
  • Decision makers often are skeptical about the authenticity of the reported data. This data obtained from the caregiver through surveys or interviews may or may not be biased or consistent with the patient’s condition.
  • The lack of consensus among clinicians, caregivers and different stakeholders of the clinical trial is another problem. Clinicians’ perspective and priorities in treating symptoms of the patient may not align with that of the caregiver. In such cases worsening quality of life of caregiver wouldn’t necessarily mean that the treatment isn’t working according to the clinician.
  • It is difficult to obtain the amount of data from the caregiver in the current setting. Filling hundreds of forms and answering hundreds of questions to arrive at the quality of life of caregiver is rather difficult. Some standardized digital form of data collection tool needs to be developed to make the process more efficient.

Conclusion

Starting from 1940s, through published articles and studies there occurred a major shift in conceptualizing health and evaluating interventions. In 1947, WHO broadened the definition of health as “a state of complete physical, mental and social well-being, and not merely the absence of disease and infirmity”. [10] Several years later, Karnofsky and Burchenal outlined the basic criteria necessary for the evaluation of new chemotherapeutic agents. These included not only the classical indicators of therapeutic success such as length of survival and objective response, but also more qualitative parameters such as performance status, reduction in symptom level, improved mood, and sense of well-being, parameters that today would be classified under the heading “quality of life.”[9]

Initially patient’s quality of life as a decision-making tool and later as an end point in clinical trials gained support from healthcare community and slowly the caregiver’s quality of life also made its place in the realm.

With more research and advancements, we have standardized tools to formally measure caregiver’s QoL and understand their burden physically, emotionally, financially and socially while taking care of the patient. The fact that caregivers are primary contributors of data for a clinical trial should be made clear in educational materials at the beginning of the study.[5] Efforts are to be made to target caregivers in recruitment efforts for clinical trials as in most cases, patients are not in a condition to search for them on their own. There must be more advancements in the clinical trial settings to overcome the challenges mentioned in this blog and include caregiver’s QoL as a surrogate end point in clinical trials because keeping patient and caregivers together at the center of studies can improve overall engagement, data quality, and research outcomes.

 

Authors – Lakshmi R, Radha Sharma

  1. https://www.ispor.org/education-training/learning-lab/conference-session/intl2023-3617/15525
  2. Caregiver Quality of Life: How to Measure It and Why – Matthew P. Martin, Mindy L. McEntee, Yash Suri, 2021 (sagepub.com)
  3. Zarit Burden Interview (apa.org)
  4. Validation of A Caregiver Strain Index by Betsy C. Robinson, PhD, Journal of Gerontology 1983, Vol. 38, No. 3, 344-348
  5. Clinical Trials Have Put Patients at the Center—But What About Caregivers? – ACRP (acrpnet.org)
  6. Caregiver Strain Index (CSI) (npcrc.org)
  7. 12-Item Short Form Survey (SF-12) – Physiopedia (physio-pedia.com)
  8. EQ-5D-3L – EQ-5D (euroqol.org)
  9. Neil K. Aaronson (1989). Quality of life assessment in clinical trials: Methodologic issues., 10(4-supp-S1), 195–208. doi:10.1016/0197-2456(89)90058-5
  10. World Health Organization: The constitution of the World Health Organization. WHO Chron 1:29, 1947