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Proposal 1721

Title of the Proposed Research

Improving the evaluation of new cancer therapies to expedite patient access

Lead Researcher

Professor Jonathan Karnon


University of Adelaide

Funding Source

The research team have received a grant from the Australian National Health and Medical research Council (NHMRC) to support the proposed research.

Potential Conflicts of Interest

One researcher is a current member of the Economic Sub-Committee of the Pharmaceutical Benefits Advisory Committee in Australia. One researcher is a current member of the Pharmaceutical Benefits Advisory Committee in Australia. One researcher is a past member of the Pharmaceutical Benefits Advisory Committee in Australia. One researcher is a past member of the Economic Sub-Committee of the Pharmaceutical Benefits Advisory Committee in Australia.

Data Sharing Agreement Date

13 April 2017

Lay Summary

In Australia, the Pharmaceuticals Benefits Scheme (PBS) provides affordable access to pharmaceutical therapies. New medicines are listed on the PBS on the basis of their clinical effectiveness and their value for money. In 2014-15, 33 of 42 (79%) submissions for medicines for advanced cancer were rejected or deferred. Most of these drugs are clinically effective, but they were not recommended for listing because the proposed price was too high.

When evaluating new cancer medicines, a common methodological issue is the extrapolation of costs and benefits beyond those observed in pivotal randomised controlled trials (RCTs). A review of decisions made by four reimbursement agencies identified methods for the extrapolation of survival data as the most important issue to be addressed by manufacturers in submissions to all agencies.

The listing of ipilimumab for metastatic melanoma illustrates the importance of extrapolation methods. The first submission in July 2011 was rejected, noting that the “extrapolation method was not appropriate”, the subsequent submission in March 2012 included changes to the extrapolation but was also rejected because the alternative extrapolation methods reduced the cost-effectiveness of the drug. The medicine was recommended for listing in November 2012. Accepted extrapolation guidelines would inform the earlier use of appropriate extrapolation methods and expedite patient access to effective medical therapies. Increasing public access to patient-level data from RCTs funded by the pharmaceutical industry provides a significant opportunity to compare alternative approaches to the extrapolation of survival benefits across a wide range of cancers and drug therapies.

The aims of the proposed research are to compare the validity of alternative extrapolation approaches over RCTs across different cancer types, and to work with an expert advisory panel to develop extrapolation guidelines to improve the evaluation of value for money, reduce the number of resubmissions for PBS listings and provide earlier access to new cancer medicines.

Data is sought for a range of available RCTs of therapies for alternative forms of advanced cancer and study designs. The analysis of the case study trials will reflect the issues and recommendations raised by the most recent literature on extrapolation methods, providing a comprehensive set of analyses to inform guideline development. An expert panel will then review the alternative extrapolation analyses and assumptions that are applied by the research team to each case study RCT. Working with the panel, the research team will develop guidelines for the extrapolation of survival data that reflect the varying characteristics of the observed data and the biological mechanisms of alternative new cancer medicines.

Study Data Provided

ROCHE-AVF2107g: A phase III, multicenter, randomized, active-controlled clinical trial to evaluate the efficacy and safety of rhumab vegf (bevacizumab) in combination with standard chemotherapy in subjects with metastatic colorectal cancer
ROCHE-BO18255 (ToGA): An open-label randomized multicentre Phase III study of trastuzumab in combination with a fluoropyrimidine and cisplatin versus chemotherapy alone as first-line therapy in patients with HER2-positive advanced gastric cancer.
LILLY-B9E-MC-JHQG: Phase III Study of Gemcitabine Plus Paclitaxel Versus Paclitaxel in Patients With Unresectable, Locally Recurrent or Metastatic Breast Cancer
LILLY-H3E-MC-JMEN: 3204A Phase 3, Double-Blind, Placebo-Controlled Study of Maintenance Pemetrexed plus Best Supportive Care versus Best Supportive Care Immediately Following Induction Treatment for Advanced Non-Small Cell Lung Cancer
LILLY-I4T-IE-JVBD: A Phase 3, Randomized, Double-Blinded Study of IMC-1121B and Best Supportive Care (BSC) Versus Placebo and BSC in the Treatment of Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Following Disease Progression on First-Line Platinum- or Fluoropyrimidine-Containing Combination Therapy
LILLY-I4T-IE-JVBE: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase 3 Study of Weekly Paclitaxel With or Without Ramucirumab (IMC-1121B) Drug Product in Patients With Metastatic Gastric Adenocarcinoma, Refractory to or Progressive After First-Line Therapy With Platinum and Fluoropyrimidine
LILLY-14X-IE-JFCC: A Randomized, Multicenter, Open-Label Phase 3 Study of Gemcitabine-Cisplatin Chemotherapy Plus Necitumumab (IMC-11F8) Versus Gemcitabine-Cisplatin Chemotherapy Alone in the First-Line Treatment of Patients With Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC) (SQUIRE)
LILLY-I4T-MC-JVBB: A Randomized, Double-Blind, Multicenter Phase 3 Study of Irinotecan, Folinic Acid, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab or Placebo in Patients With Metastatic Colorectal Carcinoma Progressive During or Following First-Line Combination Therapy With Bevacizumab, Oxaliplatin, and a Fluoropyrimidine (RAISE)

Statistical Analysis Plan

Publication Citation

The publication citation will be added after the research is published.

Summary Results

Results summary or link will be posted when available.