Real-World Evidence: A Comparison of the Australian Herceptin Program and Clinical Trials of Trastuzumab for HER2-Positive Metastatic Breast Cancer
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Estimating the real-world cost-effectiveness of a new drug relies on understanding the differences between clinical trial data (pre-reimbursement) and clinical practice (post-reimbursement). This is important for decision makers when reviewing reimbursement decisions, prices, and considering other drugs for the same condition. Differences can arise from differences in patient characteristics, but also from the availability of new evidence and evolving treatment practices. This paper examines these issues using a case study.
In 2001, the Australian Government funded trastuzumab for the treatment of HER2+ metastatic breast cancer through the Herceptin Program. The administrative arrangements of the Program resulted in rich observational data that captured information about patients treated with trastuzumab between 2001 and 2010 (n = 3830). The dataset included patient characteristics, dispensed medicines, medical service use and date of death.
Compared to participants in the clinical trials, patients were older, received more prior chemotherapies and a broader range of co-administered chemotherapies. Treatment practices differed from the clinical trials, but also changed over time. For example, in situ hybridization testing, rather than immunohistochemistry testing, and a three weekly administration schedule, rather than one weekly, were increasingly used. Compared to the clinical trials, patients administered trastuzumab with a concomitant chemotherapy generally experienced longer overall survival (151.3 weeks, 95 % CI: 142.6, 163.4), while those who received trastuzumab as a monotherapy experienced shorter overall survival (94.4 weeks, 95%CI: 86.4, 102.9). These findings may be due to a differing relative treatment effect in clinical practice, but may also be due to a range of other factors.
This analysis demonstrates the challenges for decision makers that arise because new evidence and evolving treatment practices create a gap between clinical trial data and real-world clinical practice and outcomes.
Bonny Parkinson, Rosalie Viney and Sallie-Anne Pearson contributed to the conception of the paper. Bonny Parkinson conducted the data analyses, with advice from the other co-authors. All co-authors contributed towards drafting and revising the intellectual content of the manuscript, and approved the final version for publication.
Compliances with Ethical Standards
Conflict of interest
Bonny Parkinson, Marion Haas, Stephen Goodall and Preeyaporn Srasuebkul have no conflicts of interest to declare. Sallie-Anne Pearson is a member of the Drug Utilisation Sub-Committee of the Australian Pharmaceutical Benefits Advisory Committee (PBAC). Rosalie Viney is a member of PBAC and its Economics Sub-Committee. The content of this paper does not reflect the views of the Australian Government Department of Health, the PBAC or its Sub-Committees.
The research reported in this paper is supported by an Australian National Health and Medical Research Council (NHMRC) Capacity Building Grant in Health Services Research (NHMRC ID: 571926), an Australian NHMRC Centre of Research Excellence in Medicines and Ageing Grant (ID: 1060407) and a Cancer Australia Grant (ID: 568773).
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