Real-world outcomes in oncology : assessing the value of rewardable innovation

Abstract: Recent years have seen a remarkable expansion of therapeutic options available for many forms of cancer. Evidence for the efficacy of these treatments have mainly come from randomized controlled trials, however questions often remain regarding the actual use, effectiveness and value of innovative therapies when used under the circumstances of routine clinical practice. In this thesis, we aim to assess the value and contribution of new oncology treatments for common cancers (lung, prostate, and breast) in early and/or advanced stages, based on data generated under ‘real world’ conditions in routine care. In paper I, we conducted a systematic review and mapping of the availability of real-world data (RWD) and use of evidence generated from such data (RWE), with focus on four South American countries. Findings were validated through workshops with regional experts. We identified 407 unique databases, and reported details included geographic scope, database type, population, and outcomes captured. The quality of RWD varied across countries, and we found that RWE was not consistently used to inform health care decision making. The main use of RWE was for pharmacovigilance studies, and to lesser extent for health technology assessment and for pricing decisions. In Paper II, we investigated therapeutic innovation in the care of patients diagnosed with advanced or metastatic non-small cell lung cancer (NSCLC) in the US between 1991 and 2012. Based on data from SEER-Medicare, we examined the association between the degree of innovation (measured as an innovation index or mean medication vintage) and overall survival. Results indicated that therapeutic innovation was associated with only a slightly improved 1-year survival (odds ratio (OR): 1.05 [95% confidence interval (CI): 1.04–1.05]). Paper III described the occurrence of comorbidities in patients with NSCLC based on national registry data from Sweden during 2006–2013. Comorbidities that may be associated with prognosis, disease progression or share risk factors with NSCLC were identified and assessed before and after the NSCLC diagnosis. 3,834 NSCLC patients were compared with 15,332 matched controls. The comorbidity prevalence at baseline was significantly higher in NSCLC patients with an OR of 2.44 (95% CI: 2.27–2.63), and the incidence rate ratio (IRR) of newly diagnosed comorbidities during the year after diagnosis was 32.5 (95% CI: 31.0– 34.2). In Paper IV, we described treatment patterns in patients with metastatic castration-resistant prostate cancer (mCRPC) based on health insurance data from Germany for the period January 2013 to December 2015. 447 patients were continuously enrolled for 12 months before being started on treatment with abiraterone, cabazitaxel, docetaxel, or enzalutamide. Over 70 distinct treatment pathways were identified. Abiraterone was the most commonly prescribed while cabazitaxel was the least commonly prescribed therapy. Abiraterone patients also had longest treatment duration. Paper V aimed to estimate the life-cycle value of trastuzumab for early (EBC) and metastatic (MBC) breast cancer in Sweden. Aggregate data on trastuzumab-treated patients from national registries was combined with data from RCTs and economic studies in Markov models to estimate overall survival, lifetime costs, and quality-adjusted life years (QALYs). Over 15,000 patients have been treated with trastuzumab, generating 25,844 life-years and 13,437 QALYs gained, at a monetary value of 8.7 trillion SEK. In conclusion, based on RWD, we found that innovative oncology therapies have delivered value in the care of patients with advanced or metastatic NSCLC, metastatic CRPC, and early or metastatic HER2+ BC, and other based on RWE over the past decades. However, this was not true for all new medicines introduced and the benefit derived from their use was not uniform. RWE can support value assessment of innovation, mainly in dimensions beyond therapeutic benefit.