LAUSR

We have read with interest the article by Kantarjian et al in which they report unique evidence-based data on the impact of inotuzumab ozogamicin on the quality of life of patients with relapsed/refractory acute lymphoblastic leukemia. In this randomized controlled trial (RCT), the authors found statistically and clinically meaningful better quality-of-life outcomes for patients treated with inotuzumab ozogamicin in comparison with those treated with standard-of-care chemotherapies. Differences were found in physical, role, and social functioning as well as appetite loss via a well-validated and widely adopted generic cancer quality-of-life questionnaire. These data document for the first time the impact of this drug from the unique patient’s standpoint and provide an additional evidence-based rationale for using inotuzumab ozogamicin in this population. The drug development process has historically overlooked the voices of patients, and unfortunately, this is particularly true for patients with acute leukemias, including acute lymphoblastic leukemia and acute myeloid leukemia. Indeed, in comparison with other cancer populations, the assessment of patient-reported outcomes (PROs) for acute leukemias has been a neglected issue, and methodological barriers have often been cited as the main factors preventing a sound PRO assessment in this population. These barriers include, for example, difficulty in collecting PRO questionnaires, which leads to large amounts of missing data, and a lack of disease-specific validated measures. Of course, challenges do in fact exist because assessing PROs for patients with acute diseases and often debilitating health conditions is far from easy and poses some challenges. The patient population analyzed by Kantarjian et al probably represents one of the most difficult settings for PRO assessment because patients with relapsed/ refractory acute lymphoblastic leukemia have a very poor prognosis and frequently show major quality-of-life impairments already at the time of study entry. In addition, they developed the protocol with virtually no previous PRO information available on this population, and this limited their ability to formulate well-defined PRO a priori hypotheses. The performed analyses were, therefore, somewhat explorative in nature. Nonetheless, the methodological approach to the PRO component of this RCT is remarkable. We compared the completeness of the PRO reporting of this RCT against international highquality recommended standards, and we found that some four-fifths of the recommended criteria were addressed; this is above the general level of PRO reporting typically found for other cancer malignancies. For example, reasons for missing PRO data were disclosed, whereas this was not the case in some 65% of RCTs conducted in patients with solid tumors. Moreover, the clinical significance of PRO findings, which is a crucial aspect of outcome interpretation, was also addressed in the study by Kantarjian et al, whereas this has not been the case in the large majority of RCTs (some 70%) conducted for other solid tumors. Therefore, Kantarjian et al should be applauded for demonstrating that methodological barriers are no longer insurmountable even when PROs are being assessed in a highly challenging research setting. Methodological quality is important for robustly informing patient care because poorly designed and reported PRO studies are unlikely to move science forward and to facilitate physicians in clinical decision making. In recent years, the science of PRO assessment has made outstanding advances and has provided great support to investigators in the planning, analysis, and reporting of PROs. For instance, the recently published Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT-PRO) extension is an excellent example: by indicating the key points that are to be addressed in the early phase of protocol development, it can serve as a guide to PRO implementation in future trials for researchers who are already at the stage of protocol writing.