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Assessment of Overall Survival, Quality of Life, and Safety Benefits Associated with New Cancer Medicines

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Assessment of Overall Survival, Quality of Life, and Safety Benefits Associated with New Cancer Medicines Sebastian Salas-Vega, Othon Iliopoulos and Elias Mossialos Assessment of overall survival, quality of life, and safety benefits associated with new cancer medicines Article (Published version) (Refereed) Original citation: Salas-Vega, Sebastian, Iliopoulos, Othon and Mossialos, Elias (2017) Assessment of overall survival, quality of life, and safety benefits associated with new cancer medicines. JAMA Oncology, 3 (3). pp. 382-390. ISSN 2374-2437 DOI: 10.1001/jamaoncol.2016.4166 © 2017 American Medical Association This version available at: http://eprints.lse.ac.uk/72515/ Available in LSE Research Online: April 2017 LSE has developed LSE Research Online so that users may access research output of the School. Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Users may download and/or print one copy of any article(s) in LSE Research Online to facilitate their private study or for non-commercial research. You may not engage in further distribution of the material or use it for any profit-making activities or any commercial gain. You may freely distribute the URL (http://eprints.lse.ac.uk) of the LSE Research Online website. Research JAMA Oncology | Original Investigation Assessment of Overall Survival, Quality of Life, and Safety Benefits Associated With New Cancer Medicines Sebastian Salas-Vega, MSc; Othon Iliopoulos, MD; Elias Mossialos, MD, PhD Supplemental content IMPORTANCE There is a dearth of evidence examining the impact of newly licensed cancer medicines on therapy. This information could otherwise support clinical practice, and promote value-based decision-making in the cancer drug market. OBJECTIVE To evaluate the comparative therapeutic value of all new cancer medicines approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) between 2003 and 2013. DESIGN, SETTING, AND PARTICIPANTS We used a narrative synthesis approach to systematically synthesize and analyze English, French, and Australian health technology assessments (HTAs) of all new cancer medicines licensed in the United States and Europe between 2003 and 2013. INTERVENTIONS Sixty-two new molecular entities with a primary oncology indication. MAIN OUTCOMES AND MEASURES Overall survival (OS), quality of life (QoL), and safety. RESULTS Of the 62 new active cancer molecules approved by the FDA and EMA between 2003 and 2013, 53 were appraised by English, French, or Australian HTA agencies through May 2015. Of these 53 drugs, 23 (43%) increased OS by 3 months or longer, 6 (11%) by less than 3 months, and 8 (15%) by an unknown magnitude; there was no evidence to suggest that the remaining 16 (30%) increased OS over best alternative treatments. Where overall survival gains could be quantified, all new cancer drugs were associated with a mean (SE) total increase in OS of 3.43 (0.63) months over the treatments that were available in 2003. Drug-related improvements in OS were, however, widely distributed across therapeutic targets—ranging between 0 (thyroid, ascites) and 8.48 months (breast cancers)—and were sometimes based on modeled data, indirect or nonactive comparisons, or nonvalidated evidence. Although 22 (42%) of 53 new medicines were associated with an increase in QoL, 24 (45%) were also associated with reduced patient safety. Of the 53 new cancer drugs, 42 (79%) were associated with at least some improvement in OS, QoL, or safety. CONCLUSIONS AND RELEVANCE Although innovation in the oncology drug market has contributed to improvements in therapy, the magnitude and dimension of clinical benefits vary widely, and there may be reasons to doubt that claims of efficacy reflect real-world effectiveness exactly. These findings raise important questions for clinical decision-making Author Affiliations: London School and value-based policy. of Economics and Political Science, London, England (Salas-Vega, Mossialos); Harvard Medical School, Boston, Massachusetts (Iliopoulos); Division of Hematology-Oncology, Department of Medicine, Massachusetts General Hospital, Boston (Iliopoulos); Institute of Global Health Innovation, Imperial College London, South Kensington Campus, London, England (Mossialos). Corresponding Author: Elias Mossialos, MD, PhD, London School of Economics and Political Science, JAMA Oncol. doi:10.1001/jamaoncol.2016.4166 Houghton Street, London WC2A 2A, Published online December 29, 2016. England ([email protected]). (Reprinted) E1 Copyright 2016 American Medical Association. All rights reserved. Downloaded From: http://jamanetwork.com/ by a Harvard University User on 01/04/2017 Research Original Investigation Overall Survival, Quality of Life, and Safety Benefits From New Cancer Medicines here are growing questions about the value gained from spending on what seem to be ever more expensive can- Key Points cer medicines. Rising expenditures may make it diffi- T Question What are the overall survival, quality of life, and safety cult for patients to access or remain compliant with life- benefits of recently licensed cancer medicines? extending therapies.1,2 Yet, some have argued that high prices Findings An analysis of health technology assessment reports may be justified if new and innovative treatments offer sig- found that new cancer drugs were associated with increased nificant benefits to patients.2,3 Even as studies point to gains overall survival by an average of 3.43 months between 2003 and 4 in overall survival (OS) from innovative cancer medicines, ef- 2013, with 43% increasing overall survival by 3 months or longer, forts to examine the value from spending on new cancer drugs 11% by less than 3 months and 30% were not associated with an remain stymied by a dearth of systematic evidence on their increase in overall survival. Most new cancer drugs improved clinical risks and benefits. This lack of evidence makes it dif- quality of life, and were associated with reduced patient safety. 5 ficult for the public to demand more from innovation, and, Meaning The added benefits of new cancer medicines vary where costs factor into the decision-making process, for cli- widely across and within therapeutic indications and may be based nicians and patients to balance preferences for the expected on modeled data, indirect or nonactive comparisons, or impact of treatment against rising drug expenditures. nonvalidated evidence. One difficulty in characterizing the clinical impact of new cancer drugs is the multiplicity of outcome measures. Overall survival has traditionally been taken as the gold tific evidence is used to inform clinical practice, and how much standard among oncology efficacy endpoints.6,7 The United value is generated from cancer drug spending. States Food and Drug Administration (FDA), for its part, des- ignates OS as the only “universally accepted” and the “most 8 reliable” direct measure of benefit in oncology drug trials. Methods The European Medicines Agency (EMA) similarly states that convincing favorable effects on OS are, from a clinical and Inclusion and Exclusion Criteria methodological perspective, the “most persuasive outcome” All new molecular entities (NMEs) approved by the FDA and of oncology trials.9 As policymakers adopt new regulations EMA between 2003 and 2013 with a primary indication for on- to expedite access to medicines for serious conditions,10,11 cology were eligible for inclusion. This study focused exclu- interest has grown in measuring effectiveness through sur- sively on primary indications, which are likely to reflect main rogate markers.12 These, however, are not yet systematically intended use. Drug inclusion criteria were adapted from a pre- measured by regulators8,13 and still have inconsistent or vious study by Roberts et al.22 Because this study did not use uncertain predictive clinical value.14,15 Despite its potential or access patient-level data the London School of Economics limitations, the American Society for Clinical Oncology’s and Political Science determined that ethical approval was not (ASCO) recently published16 Value Framework in fact required. recommends that efficacy benefits be measured through progression-free survival or response rates only if OS is not Drug Appraisals reported.17 In addition to efficacy measures, quality of life Evaluations of the clinical impact of new cancer drugs were (QoL) and safety are also used by regulators and clinicians to obtained from English, French, and Australian agency HTAs fully consider the impact on how patients feel and function published through May 2015. These agencies regularly pub- owing to treatment.17-19 lish HTAs in the English language, and are required to evalu- To shed light on the clinical risks and benefits from new ate the clinical impact of new medicines in relation to exist- cancer drugs, this study took a narrative synthesis approach ing standards of treatment that would most likely be replaced to review regulatory assessments of the impact on OS, QoL, by the new intervention.23-25 Health technology assessments and safety from all cancer medicines newly licensed in the US were selected for review if they pertained to the same target and Europe over the past decade. Since US licensing deci- condition as the first FDA-approved indication. If multiple re- sions do not require proof of comparative efficacy and may not ports evaluated the same target condition, we selected the lat- consider OS benefits under accelerated licensing est report that most closely matched the first FDA-approved procedures,20,21 we extracted
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