Development of an MF patient reported outcome (PRO) tool for FDA qualification: Comprehensive literature search and physician cognitive debriefing results

Geyer H., Kosiorek H., Dueck A., Slot S., Zweegman S., Kiladjian J.J., Boekhorst P., Schouten H., Sackmann F., Fuentes A., Hernandez-Maraver D., Pahl H., Stegelmann F., Doehner K., Bonatz K., Reiter A., Boyer F., Etienne G., Ianotto J.C., Ranta D.Roy L., Cahn J.Y., Harrison C., Radia D., Muxi P., Maldonado N., Besses C., Cervantes F., Johansson P., Barosi G., Passamonti F., Andreasson B., Samuelsson J., Birgegard G., Sun X., Xu J., Zhang P., Xu Z., Barbui T., Barbui T., Senyak Z., Grieshammer M., Rambaldi A., Ferrari M., Lehmann T., Scherber R., Mesa R.

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Myelofibrosis (MF) is recognized for its debilitating constitutional symptoms, splenomegaly, profound cytopenias and inflammatory state. Current MPN PROs (MF-SAF, MPN-SAF and MPN-10) have proven sensitive for symptom detection. Formal FDA qualification requires that these tools integrate a comprehensive literature search of previously reported symptoms as well as complete physician cognitive debriefing. Aims: In this investigation, we aimed to complete these required steps to ascertain the most prevalent and pertinent MPN symptoms for PRO inclusion. Methods: Literature Search: An initial review of the published literature was performed using OVID Medline®. The Medical Subject Headings (MeSH) terms included 'primary myelofibrosis' or 'MF', 'Myeloid metaplasia' and 'agnogenic myeloid metaplasia' which were meshed with 'symptom' or 'signs and symptoms' and limited from 1980 to 2011. Articles that were not original research or in the English language were excluded. Articles were then individually reviewed for content with further exclusion of case reports where search terms occurred concurrently with other medical conditions, articles presenting in-vitro data and articles with a primary focus on pharmacotherapy that utilized the MPN-SAF, MPN-SAF TSS or MF-SAF. Articles were then evaluated for all symptoms and recorded by the number of publications they were reported in. Cognitive Debriefing: International MPN specialists were contacted via email to complete the Physician Cognitive Debriefing Evaluation via a REDCAP® survey. Implied consent was provided through survey completion and demographic data was recorded. Responders were asked a series of questions on each symptom acquired through the literature search, along with three free-standing questions on MF PRO development. Thirteen responders were also contacted to complete an in-person interview and respond to eight questions on MF-PRO development. Descriptive statistics were used for data analysis. Results: The OVID Medline search yielded 166 articles for MF which were then individually reviewed. A total of 30 symptoms were extracted from the literature and recorded for incorporation into the REDCAP survey. The survey was distributed to 48 MPN specialists and 17 (35.4%) agreed to participate. Most responders were Caucasian (94.1%) and male (76.5%) with >5 years experience (94.1%) as physicians. Providers saw between 1-5 (58.8%), 6-10 (23.5%) or >10 (11.8) MF patients per week and most held primary practices in Europe (70.6%). Survey responses to symptom questions are provided in Figure 1. During in-person interviews, some providers felt that a different list of symptoms should be provided to patients with: early vs late MF (61.5%), primary vs secondary MF (7.7%) and clinical trial settings vs office environments (23.1%). Most providers felt that 'inactivity' (100%), 'fever' (92.3%) and 'weight loss' (92.3%) were signs as opposed to symptoms of the disease, though should still be included in the PRO (92.3% for each). Most providers believed that the ideal survey length should be between 10-20 questions. Two providers believed that 'health economics' and 'activities of daily living' should be integrated into a final PRO. Summary/Conclusions: Results of the literature search and Physician Cognitive Debriefing support that the MPN-SAF currently addresses the most frequent and symptomatic MF symptoms, with the exception of four items (dyspnea, easy bruising, arthralgias, nausea). Addition Patient Cognitive Debriefing is required to ensure that the final PRO is comprehensive of the most important symptoms to patients. (Figuer Presented).
Original languageEnglish
Pages (from-to)564
Number of pages1
JournalHaematologica
Volume101
Publication statusPublished - 2016

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