PF552 PATIENT‐REPORTED OUTCOME MEASURES IN CLINICAL STUDIES FOR MYELODYSPLASTIC SYNDROMES AND ACUTE MYELOID LEUKEMIA: A LITERATURE REVIEW AND LANDSCAPE ANALYSIS
Authors: H. Chevrou‐Séverac, J. Lambert, I. Savre, P. Koochaki, L. Gaugler, I. Stojkov, U. Siebert, R. Stauder
Journal: HemaSphere (2019)

Background: The integration of patient‐reported outcome measures (PROMs) in clinical studies and in daily practice has been advocated by patients, providers, payers, and authorities. In cancer, PROMs such as EORTC‐QLQ‐C30 and FACT‐G are used. However, for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), these PROMs might not sufficiently capture the specific relevant symptoms and concerns of these patients. Aims: To assess the use of generic and disease‐specific PROMs in published and ongoing clinical studies, and to describe the PROMs landscape in MDS and AML. Methods: A comprehensive literature review was performed using MEDLINE/EMBASE (Jan 2000–Jan 2018) to identify PROMs published in clinical trials of MDS and AML treatments, supplemented by a review of studies in ClinicalTrials.gov (Jan 2013–Jan 2018). Additionally, PROMs included in approved drug labeling claims for MDS and AML (Jan 2000–Dec 2017) were retrieved from the Mapi Research Trust PROLABELS™ database and FDA/EMA websites. Guidelines issued by regulatory agencies (FDA, EMA, NICE, IQWiG) were reviewed using the Mapi Research Trust PROINSIGHT™ database to identify any patient‐reported outcome (PRO)‐related recommendations. The results are summarized in systematic evidence tables. Results: We identified 246 published studies in MDS and AML where PROMs were used to assess general quality of life (QoL) and/or symptoms. In total, 94 different PROMs were used in 159 studies in MDS, whereas 123 PROMs were used in 142 studies in AML. The most frequently used PROMs in AML and MDS studies were generic instruments (e.g. EORTC QLQ‐C30, FACT‐An, SF‐36, FACT‐BMT), whereas disease‐specific ones, namely QUALMS and QOL‐E in MDS, and FACT‐Leukemia (Leu) and EORTC QLQ‐Leu in AML, were used in a minority of studies (Table). From ClinicalTrials.gov, 19 different PROMs in 22 ongoing MDS studies were identified (52% phase 2, 12% phase 2/3, 36% phase 3), while 13 different PROMs were reported in 31 studies in AML (57% phase 2, 2% phase 2/3, 41% phase 3). For both indications, the most frequently used PROM was EORTC‐QLQ‐C30 (8/22 studies in MDS and 17/31 in AML). In total, 14 drugs were reviewed in AML or MDS for approval between 2000 and 2017. Two drugs, approved for MDS by the EMA, had a PROM evaluation used as a secondary endpoint mentioned in their label (EORTC QLQ‐C30 data reported in the azacytidine label and FACT‐G, FACT‐An, and EQ‐5D data reported in the lenalidomide label). Out of 4 FDA‐approved MDS drugs, none had PRO data reported in their labeling claims. Eight drugs for AML were approved by the FDA (n = 6) or EMA (n = 2), none of which included a PROM evaluation in their labeling claim. No specific guidelines for PRO use in trials of MDS/AML treatments were identified. The EMA guideline appendix on evaluation of cancer treatments (Appendix 2, 2016) recommends the consideration of PROs in future guidelines and trials due to the impact of MDS on QoL, without specifying any generic or disease‐specific PRO instrument. Summary/Conclusion: Our review showed that the EORTC QLQ‐C30 is by far the most frequently used cancer‐specific PROM in both MDS and AML studies. This PROM assesses both QoL and symptoms. Apart from the QOL‐E for MDS and the FACT‐Leu for AML, this research indicated an underuse of disease‐specific PROMs for these 2 indications. However, other disease‐specific instruments such as the QUALMS and the AML‐QoL are in development and might be worth considering in the future. image