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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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Abstract

Introduction

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.

Methods

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.

Results

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.

Conclusion

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.

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Notes

  1. Likely because they were enrolled shortly before 31 March 2010.

  2. The accuracy of the recorded date of death of patients whose first treatment request occurred after their date of death was tested by comparing the recorded date of death with the last date that any MBS or PBS claim was made. As no patients made PBS or MBS claims after their recorded date of death, the date of death was probably correctly recorded and the first date that trastuzumab was requested may have been incorrectly recorded.

  3. Excluding the first request, which would include the loading dose.

  4. Based on the average time between treatment requests, this assumption appeared reasonable.

  5. 60 mg vials were not available during the time period of this analysis (see Table 2).

  6. This affected 460 patients.

  7. The reason for the cessation of a chemotherapy not being considered as an indicator of progression is that many chemotherapies are ceased due to toxicities or a set number of cycles are planned.

  8. Unique cytotoxics. This is not the equivalent of lines of chemotherapy—some patients may have received the chemotherapies in combination with others.

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Author contributions

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.

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Authors and Affiliations

  1. Centre for the Health Economy, Macquarie University, Room 540, 5th Floor, Building E4A, Sydney, NSW, 2109, Australia

    Bonny Parkinson

  2. Centre for Health Economics Research and Evaluation (CHERE), University of Technology Sydney, Sydney, NSW, Australia

    Bonny Parkinson, Rosalie Viney, Marion Haas & Stephen Goodall

  3. Medicines Policy Research Unit, Centre for Big Data Research in Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia

    Sallie-Anne Pearson

  4. Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia

    Preeyaporn Srasuebkul

  5. Faculty of Pharmacy, The University of Sydney, Sydney, NSW, Australia

    Sallie-Anne Pearson

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  1. Bonny Parkinson
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Correspondence to Bonny Parkinson.

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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.

Funding

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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Parkinson, B., Viney, R., Haas, M. et al. Real-World Evidence: A Comparison of the Australian Herceptin Program and Clinical Trials of Trastuzumab for HER2-Positive Metastatic Breast Cancer. PharmacoEconomics 34, 1039–1050 (2016). https://doi.org/10.1007/s40273-016-0411-2

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