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In this article David Steensma, MD FACP at the Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts USA discusses how to incorporating the Patient’s Voice into MDS Care and Research.

Measuring quality of life: how to capture the voice of patients

Most studies of new treatments for myelodysplastic syndromes (MDS) track measurable changes in patients’ full blood counts and bone marrow cells, since improvements in these ‘objective’ parameters tend to correlate with better physical functioning, reduced symptoms, and sometimes even longer life. But the day-to-day experience of the patient is fundamentally important too, both in the context of clinical trials and in more routine haematology care.

Increasingly, investigators are capturing the voices of patients through the use of formal surveys that measure what are called ‘Patient Reported Outcomes’ (PROs), which can give insight into ‘health-related quality-of-life’ (HR-QOL).

While it has long been recognised that HR-QOL is critically important, the advent of PROs is a welcome development as certain symptoms can only be reported by patients and are not easily measured by an outside observer. For example, a doctor may notice when the patient in the clinic chair in front of her appears uncomfortable and fidgety, dozes off during conversation, or is breathing rapidly and audibly. But only that patient can tell the doctor just how much he is actually bothered by pain, anxiety, fatigue or breathlessness.

In addition, the influence of a diagnosis like MDS on patients’ daily lives, including the degree to which disease-associated symptoms get in the way of important activities such as exercise, cooking, bathing, working, or interacting meaningfully with family, is best reported by the patients themselves.

Patient Reported Outcomes (PRO)

There are many PRO tools with diverse designs. What all PRO tools have in common is that patients are asked a series of questions about the presence, absence, or severity of particular symptoms or concerns. Each ‘domain’ in a PRO survey instrument includes questions about a specific area of focus such as fatigue, sleep disturbance, or financial worries.

Some survey instruments explore a single domain like depression, or are designed for use by patients with a single disease such as dementia. Others are designed to assess health status more generally.

Some PROs are well-validated and have been employed in hundreds of studies, while others have been used only on one or two occasions.

The most useful PROs for clinical trial purposes are those that are most specific to the disease or problem being measured and that have been benchmarked in a large number of people with the condition of interest.

Widely used general PRO tools include:

  • The European Organization for the Research and Treatment of Cancer 30-question Quality of Life Questionnaire (EORTC QLQ-C30), which has been translated into over 100 languages and used in more than 3,000 studies to date.
  • The Psychological General Well-Being Index (PGWBI), which has been part of thousands of studies and is not limited to haematology-oncology.

More narrowly focused tools include:

  • The Brief Fatigue Inventory (BFI), which measures specifically the severity and impact of fatigue - the most common MDS-related symptom.
  • The series of Functional Assessment for Cancer Therapy (FACT) instruments developed by Chicago social scientist Dr. David Cella. The dozens of FACT tools are well validated in patients with cancer and blood disorders. One of the most commonly used is ‘FACT-An’, which specifically assesses the influence of anaemia-associated symptoms and transfusion burdens on patient’s quality of life. Given the frequency with which patients with MDS suffer from anaemia (over 90% are anaemic at diagnosis), the FACT-An tool is commonly used in MDS clinical trials, even though it was not developed specifically for MDS.

Dr. David Steensma on MDS research | Dana-Farber Cancer Institute

How can PRO tools help in clinical consultations?

PRO tools were first developed for use in health care services research, but are now integrated into almost every major clinical trial in haematology-oncology. We are also starting to see these tools used as part of general clinical care, where patients are being asked to complete surveys (either on paper or on an electronic tablet) while in the waiting area prior to an appointment.

Formally capturing PROs in practice allows the recording of trends in symptoms, and may save time in the clinic or allow triaging of which patients most need to be seen for consultation. For instance, in our practice in Boston, older patients are assessed using a PRO at the time of initial consultation and those with a high degree of symptoms specialist in addition to the haematologist.

In addition, some patients may be uncomfortable bringing up certain types of symptoms with their doctor (e.g. depression, anxiety, sexual concerns). But if the patient is ushered into the consultation room having completed a PRO instrument that discreetly highlights those symptoms, the doctor can then inquire specifically about such problems and offer help. This may be especially beneficial in some geographical areas where patients are more hesitant to discuss symptoms.

I was recently on a flight from Florida to Boston in which the person in the middle seat in the row in front of me began to discuss her bothersome rash, prompting a soliloquy from her neighbour about hip pain and sciatica and a later mention from the seatmate on the other side about how difficult it had been for her to get her infant to breastfeed properly. I was reminded that Americans tend to ‘over-share’, having few qualms about discussing intimate physical complaints with a casual acquaintance or someone they’ve just met. During the 2 years I spent in Oxford, I noted that patients in the UK tended to be a bit more reserved!

PRO scores and new drug approvals

Increasingly, PRO scores are reviewed by regulatory agencies considering new drug approvals, and are part of the deliberations of health technology assessment bodies and insurers when deciding which new drugs are worth paying for. For instance, ruxolitinib (Jakafi) was approved by the US Food and Drug Administration (FDA) in November 2011 for treatment of patients with the bone marrow disorder myelofibrosis, and the European Medicines Agency (EMA) approved ruxolitinib in April 2012.

Those regulatory approvals were primarily based on striking medication-induced improvements in patient scores on a disease-specific PRO tool called the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) designed by Drs. Ruben Mesa of Mayo Clinic and Claire Harrison in London and their colleagues. MPNSAF scores were supplemented by objective measures of radiographic improvement of spleen dimensions, since spleen enlargement is common in myelofibrosis, unlike MDS.

Once EMA approval had been received, the UK National Institute of Health and Clinical Excellence (NICE) and the Scottish Medicine Consortium (SMC) for NHS Scotland carefully considered MPN-SAF PRO scores and decided for which types of patients with myelofibrosis they would fund the drug.

How are patient-friendly PRO tools developed?

Of course, if PRO tools are very long and cumbersome, they are less likely be used, so when a new PRO tool is designed, considerable effort goes into developing the shortest tool that will reliably gather the desired information.

Developing a PRO tool is a multi-step process. For instance, when my Harvard colleague Gregory Abel and I developed the first MDS-specific PRO, Quality of Life in in Myelodysplasia Scale #1 (QUALMS-1) in 2014-2015, we began with a series of structured interviews with patients and caregivers, supplemented by findings from focus groups. We compared results to FACT-An and EORTC QLQ-C30 measurements from the same patients, and administered the tool on multiple occasions just in case patients were having a particularly bad day on the day they used the PRO.

We then used statistical tools with the help of experts in measuring HR-QOL to figure out which questions provided the most information and provided information that was not redundant and therefore should be incorporated into the final PRO, as well as which domains were independent of other domains. QUALMS-1 has been validated in international populations (Abel G et al Haematologica June 2016) and is now being used in several ongoing MDS prospective clinical trials.

Silver lining

One unexpected finding from our work on QUALMS-1 was that some patients noted a ‘silver lining’ from their MDS diagnosis.

A subset of patients expressed greater appreciation of the value of life in the context of regular reminders of its fragility, and they told us that their MDS diagnosis favorably influenced interactions with friends and family and made them appreciate each day more. We called this the ‘existential domain’, and it is an important part of the QUALMS-1 measurements.

It is a welcome development to see HR-QOL metrics and PROs incorporated into medication trials and haematology clinics. After all, at the end of the day it is the patient who has the disease and who is best able to judge whether a treatment makes a meaningful difference beyond merely altering measurable numbers.

MDS UK Nov 2018 Newsletter

This article was first published in the 9th Edition of the MDS UK Newsletter. If you haven't received it, please contact us.
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