by Jill Holdren
Last month on September 14th, Lisa Schlager, FORCE VP of Public Policy, and I went to St. Louis, Missouri to give comments at the Institute for Clinical and Economic Review’s (ICER) meeting on the clinical effectiveness and value of PARP inhibitors in the treatment of ovarian cancer. The meeting was one of the final steps in a six month process that began with the publication of a draft scoping document in March and ultimately led to the release of a final report in late September.
Advisory Council Meeting
The purpose of the meeting was to convene the Midwest Comparative Effectiveness Public Advisory Council (CEPAC) to discuss the evidence report produced over the previous six months. This was followed by a council vote on a series of questions regarding the value and cost-effectiveness of the PARP inhibitors olaparib, rucaparib, and niraparib as treatment for recurrent ovarian cancer among women with BRCA mutations and as maintenance therapy in women with platinum-sensitive disease.
While ICER is an independent nonprofit, its analyses may be used by health plans to determine what therapies they will cover and how much they will pay for them. Thus, patient stakeholders participation in these processes is critical to ensure that the analyses reflect the hereditary cancer community’s experiences, perspectives, and interests. To that end, in August FORCE reviewed the draft evidence report and submitted comments expressing grave concerns, and, in September, Lisa and I flew to St. Louis to reiterate these concerns, put faces and individual stories to the ovarian cancer experience, and talk about the real-world benefits of PARP inhibitors for our community.
Unfortunately, despite our efforts and the efforts of many other groups and individuals, ICER’s final report does not reflect the value of PARP inhibitors to the ovarian cancer community in general, and to the HBOC community FORCE serves in particular. ICER concludes that in terms of evidence of clinical effectiveness, olaparib, and rucaparib are promising but inconclusive in the treatment of BRCA-mutated recurrent disease and receive a grade of C+ -- meaning high certainty of at least a comparable net health benefit when used as maintenance therapy relative to placebo (i.e., surveillance alone) -- in platinum-sensitive disease (see Table 1). In terms of cost-effectiveness, ICER concludes that, except perhaps for olaparib in BRCA-mutated recurrent ovarian cancer, PARP inhibitors are not cost-effective.
The votes by the CEPAC are shown in Table 2. Of potential concern is that the votes do not appear to consistently reflect the conclusions of the report nor the input of the patient and patient advocacy community.
Table 1. ICER’s Evidence Ratings for PARP Inhibitors in the Treatment of Ovarian Cancer.
Shortcomings in ICER report
We believe that ICER’s report is flawed in several ways that make its conclusions about both the value and cost-effectiveness of PARP inhibitors problematic. Specifically:
- The Timing of the Report is Premature. There is simply not enough information on outcomes or comparators to make detailed assessments about the value and cost-effectiveness of PARP inhibitors. Throughout its report, ICER acknowledges this limitation and yet, it finalized a report that could severely restrict access to medications that thus far appear to play an important and unique role in treating ovarian cancer recurrence. At the meeting, when Lisa directly asked the question, “Why are we doing this right now?”, an ICER representative answered, “This is the time for these decisions to be made even in the absence of data” -- a remarkably disturbing statement from an organization that prides itself on its data-driven approach to assessing therapies.
- The economic analysis was flawed in important ways. The analysis that determined the cost-effectiveness and value of the therapies was based on a number of flawed assumptions, ultimately underestimating the value of PARP inhibitors compared to other treatments or lack of treatment, including:
- The studies chosen as comparators were not equivalent to the stated PARP patient populations in terms of the number of prior treatments, platinum sensitivity, or BRCA mutation status. As such, it is not possible to draw accurate conclusions on the clinical effectiveness, which in turn informs the value.
- ICER used less than comprehensive cost estimates for adverse events of alternate therapies.
- ICER weighted PARP inhibitor toxicity too heavily. Toxicity is generally not an ongoing issue with PARP inhibitors. Rather, once the right dose is found for an individual patient, toxicities tend to be low and side-effects negligible.
- The analysis fails to account for lost productivity resulting from the side effects patients commonly experience with traditional cancer therapies, which is generally significant.
- ICER’s decision to forgo a societal analysis of lost productivity due to “the typically advanced age” of ovarian cancer patients seriously undervalues the impact of PARP inhibitors. In women with BRCA mutations, ovarian cancer frequently occurs in our 30s and 40s and 50s, when we are immersed in careers, civic engagement, and parenting.
- Progression-Free Survival (PFS) is a critically important outcome for many patients. Despite hearing of its importance from many patients, ICER gives little weight to the value of Progression-Free Survival, one of the clear benefits of PARP inhibitor therapy for many women. PFS is the most important clinical outcome to many women with advanced ovarian cancer. By not acknowledging this and giving appropriate weight to PFS in their value analysis, ICER again significantly underestimates the value of PARP inhibitors.
- PARP Inhibitors are an investment in innovation made not only by pharmaceutical companies but by the patients who participated in clinical trials. PARP Inhibitors represent a decade-long research investment with tens of thousands of people taking the risk to volunteer for studies. While these agents may appear costly on an individual scale, there are significant societal benefits given the investment in development, savings in productivity, improved quality-of-life, and potential for further improvement in this therapeutic approach by using the agents at an earlier stage of disease and in concert with other therapies.
In short, ICER’s final evidence report is based on inadequate data and mischaracterizes a number of key points that impact the value assessment. It lacks meaningful patient input – input that should be integrated into the analysis and would change the value calculus. We are deeply concerned that this report will adversely impact both the ability of ill women to access critical drugs and the ability of doctors and scientists to further study, understand, and improve on their function and value. FORCE has advocated for PARP inhibitors since their development a decade ago and will continue to advocate for patient access to these and other promising agents.
Table 2. Evidence Votes of the Midwest CEPAC on PARP Inhibitors in Ovarian Cancer, Sept. 14, 2017
I'm grateful to FORCE for giving me the training and opportunity to participate as a volunteer in the ICER meeting and in other advocacy efforts for our community through its Research Advocate Program. As a FORCE volunteer, I am able to help the hereditary cancer community in a small way, and, at the same time, learn a tremendous amount, have new experiences, and meet interesting people. I highly recommend becoming a FORCE volunteer if you're not one already.
 ICER “is an independent non-profit research organization that evaluates medical evidence and convenes public deliberative bodies to help stakeholders interpret and apply evidence to improve patient outcomes and control costs. ICER receives funding from government grants, non-profit foundations, health plans, provider groups, and health industry manufacturers”.
 The Midwest Comparative Effectiveness Public Advisory Council (CEPAC) is a core program of ICER. The Midwest CEPAC convenes clinicians, patients, and payers three times each year at public meetings to review objective evidence reports.
Jill Holdren is a BRCA1 mutation carrier and a survivor of ovarian cancer. She has a background in environmental science and public health and has been a volunteer with FORCE since January of 2016, first as a research advocate, then as a peer navigator, and finally as a peer group co-leader. She lives in Boulder, Colorado and enjoys sunny days, long hikes, and getting her hands dirty in her garden.