Reply to the letter to the editor ‘On the underreporting of health-related quality of life and regulatory approval’ by Bhamidipati et al.
Authors: M. Di Maio, L. Marandino, F. Perrone
Journal: Annals of Oncology (2019)

We are pleased that our publication [1.Marandino L. La Salvia A. Sonetto C. et al.Deficiencies in health-related quality of life assessment and reporting: a systematic review of oncology randomized phase III trials published between 2012 and 2016.Ann Oncol. 2018; 29: 2288-2295Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar] met the interest of Bhamidipati et al. [2.Bhamidipati D. Anand S. Gothwal A. et al.On the underreporting of health-related quality of life and regulatory approval.Ann Oncol. 2019; 30: 657-658Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar] Data reported in their correspondence are based on the analysis of trials leading to Food and Drug Administration approval for solid or hematologic malignancies, between 2009 and 2018, which is a period of time entirely including the time-frame considered in our analysis. Their results are very similar to ours, showing sub-optimal adoption of quality of life (QoL) among end points and poor QoL reporting in publications. We strongly believe that QoL assessment is crucial to evaluate the benefit–harm balance of new anticancer treatments. Especially when trial results show a questionable clinical relevance due to the adoption of surrogate endpoints, like progression-free survival (PFS), QoL results should be considered of paramount importance to prove the added value of a new treatment [3.Nishikawa G. Prasad V. Diagnostic expansion in clinical trials: myocardial infarction, stroke, cancer recurrence, and metastases may not be the hard endpoints you thought they were.BMJ. 2018; 362: k3783Crossref PubMed Scopus (6) Google Scholar]. In the database, we used for our published analysis [1.Marandino L. La Salvia A. Sonetto C. et al.Deficiencies in health-related quality of life assessment and reporting: a systematic review of oncology randomized phase III trials published between 2012 and 2016.Ann Oncol. 2018; 29: 2288-2295Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar], 87 publications of trials conducted in the advanced/metastatic setting showed a positive result based on a primary endpoint different from overall survival (OS), mostly PFS [4.M Di Maio, L Marandino, F. Perrone Re: diagnostic expansion in clinical trials: myocardial infarction, stroke, cancer recurrence, and metastases may not be the hard endpoints you thought they were. https://www.bmj.com/content/362/bmj.k3783/rapid-responses (2 February 2019, date last accessed).Google Scholar]. Of these 87 publications, the majority (67) did not report positive OS results in the primary publication. Although this situation (a positive result in a surrogate end point, without evidence of benefit in OS) is exactly the situation requiring the availability of QoL data in order to judge the clinical relevance of the results, disappointingly 21 of those studies (31.3%) did not include QoL among study end points, and 40 publications (59.7%) did not present any QoL results. In accordance with the analysis presented by Bhamidipati et al., these results highlight the lack of QoL information for several new treatments that, on the basis of positive results, are subject to evaluation for regulatory approval. Bhamidipati et al. underline the recent position of most important scientific societies, which led to the inclusion of QoL within the evaluation tools of treatment value. As a matter of fact, the attention of scientific community to these issues is recently increasing. At 2018 ESMO meeting, a whole session of oral presentations about metastatic breast cancer was dedicated to QoL results of positive and potentially practice-changing randomized trials. Dr. Leslie Fallowfield, who acted as discussant of that session, recently commented our analysis [5.Fallowfield L.J. Quality of life assessment using patient-reported outcome (PRO) measures: still a Cinderella outcome?.Ann Oncol. 2018; 29: 2286-2287Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar] highlighting that unfortunately QoL is often still considered a ‘Cinderella outcome’. Also ASCO, at the end of 2018, dedicated a post to this specific topic, emphasising QoL as a key element for the assessment of new treatments, even more in those situations where the statistical significance of results conflicts with their clinical relevance [6.NS. El Saghir Quality of Life, Clinical Trials, and Clinical Practice. https://connection.asco.org/blogs/quality-life-clinical-trials-and-clinical-practice (2 February 2019, date last accessed).Google Scholar]. As Bhamidipati et al. state, the burden now falls to regulatory agencies, which should make efforts to encourage the inclusion and timely reporting of QoL issues. On the other hand, we believe that also the scientific community should make efforts to pursue a more rigorous methodology in QoL assessment and reporting. None declared.