Swaying sickle cell research forward in support of patient reported outcomes

Sickle cell disease (SCD) is a genetic disorder of the blood that leads to severe morbidity and early mortality. It is the most common disease detected by newborn screening efforts in the United States and affects millions worldwide. The disease reduces life expectancy by approximately 30 years compared with the life expectancy of the general population. Furthermore, the disease is to known to limit the quality of life as severely as does end-stage renal disease requiring hemodialysis, as measured by the Medical Outcome Study 36 item Short Form (SF-36). The SF-36 and the Pediatric Quality of Life Inventory (PedsQL) tools have been used in multiple studies of people with SCD to measure bodily pain, social functioning, physical functioning and mental health, showing substantial impairment in Health-related Quality of Life (HRQOL) for both children and adults. These tools have also been used to examine HRQOL in patients living in other countries and for the PedsQL there is data that it is responsive to acute pain in children with SCD. There are no tools that have been shown to be responsive to changes in chronic pain over time in children or adults with SCD. The Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) was specifically designed to assess HRQOL in people with SCD, this tool can measure a number of outcomes including emotional impact, sleep impact, social impact, and pain impact, but does not collect data on patients' views of how the disease is treated and managed. There are no validated global assessments of how SCD affects patients on a daily basis. Global patient assessment tools are used in a number of other diseases. One example is rheumatoid arthritis where the Patient Global Assessment (PGA) is used to assess response to treatment. These instruments have been validated and incorporated into research studies to assess response to new treatments and are even used in routine clinical practice. The use of the PGA in patients with RA allows for a more holistic assessment of disease that provides more information than measures of inflammation and joint damage. Rigorous measurement of outcomes that are relevant to patients is necessary to demonstrate quality of health and health care delivery, especially in a disease such as SCD where subjective symptoms such as fatigue and pain are often the only measure of disease activity. In this issue of the American Journal of Hematology, Osunkwo and colleagues report a multi-country survey across six geographic regions to assess the impact of SCD on those affected with the goal of understanding overall disease burden and not just HRQOL. They surveyed over 2000 children and adults from 16 countries. They found that sixty percent of respondents felt that SCD had a high impact on emotional well-being, with many worrying that their disease would worsen over time. Sixty-two percent of respondents reported a desire to start receiving or to continue to receive professional emotional support. Only 33% of those surveyed were employed, with subjects reporting that SCD had a substantial impact on their careers. Of the subjects surveyed under the age of 18 over 50% reported that SCD had a high impact on school achievement. Importantly, the three most common symptoms, excluding vasoocclusive crises (VOC), subjects reported were fatigue, bone aches and headaches. Those that reported these symptoms reported a higher impact of SCD on aspects of daily life, emotional well-being, schooling and employment than those that did not report these symptoms. Subjects were asked about the occurrence of VOC in the prior 12 months with the mean number of events of 5.3. Twentyfour percent of these events were managed at home. When asked why subjects chose to treat these events at home, almost 40% reported the reason as being a poor experience at the hospital or emergency room. Despite the lack of a validated instrument, the global steering committee that developed the Sickle Cell World Assessment Survey (SWAY) used a similar methodology in developing their survey tool as the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group uses in identifying core domains for survey tools for rheumatologic disease. Both groups include a structured enquiry with stakeholders of their views on domains of importance. Note, OMERACT has been developing tools to assess rheumatologic disease for over 25 years and these tools are incorporated not only in research but Received: 29 December 2020 Accepted: 29 December 2020