, Volume 34, Issue 10, pp 1039–1050 | Cite as

Real-World Evidence: A Comparison of the Australian Herceptin Program and Clinical Trials of Trastuzumab for HER2-Positive Metastatic Breast Cancer

  • Bonny ParkinsonEmail author
  • Rosalie Viney
  • Marion Haas
  • Stephen Goodall
  • Preeyaporn Srasuebkul
  • Sallie-Anne Pearson
Original Research Article



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.


Trastuzumab Vinorelbine Pharmaceutical Benefit Scheme Concomitant Chemotherapy Reimbursement Decision 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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.

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).

Supplementary material

40273_2016_411_MOESM1_ESM.docx (69 kb)
Supplementary material 1 (DOCX 68 kb)


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Bonny Parkinson
    • 1
    • 2
    Email author
  • Rosalie Viney
    • 2
  • Marion Haas
    • 2
  • Stephen Goodall
    • 2
  • Preeyaporn Srasuebkul
    • 4
  • Sallie-Anne Pearson
    • 3
    • 5
  1. 1.Centre for the Health EconomyMacquarie UniversitySydneyAustralia
  2. 2.Centre for Health Economics Research and Evaluation (CHERE)University of Technology SydneySydneyAustralia
  3. 3.Medicines Policy Research Unit, Centre for Big Data Research in Health, Faculty of MedicineUniversity of New South WalesSydneyAustralia
  4. 4.Faculty of MedicineUniversity of New South WalesSydneyAustralia
  5. 5.Faculty of PharmacyThe University of SydneySydneyAustralia

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