April 17, 2017
Submitted electronically to: [email protected]
Institute for Clinical and Economic Review
Two Liberty Square, Ninth Floor
Boston, MA 02109
Re: Feedback on ICER’s Dupilumab and Crisaborole for Atopic Dermatitis: Effectiveness and Value Draft Evidence Report
Dear Dr. Pearson:
On behalf of the Institute for Patient Access, I thank you for the opportunity to provide feedback on the Institute for Clinical and Economic Review’s draft report regarding the cost-effectiveness of dupilumab and crisaborole for treating atopic dermatitis.
About the Institute for Patient Access
The Institute for Patient Access (IfPA) is a physician-led policy research organization dedicated to maintaining the primacy of the physician-patient relationship in the provision of quality healthcare. To further that mission, IfPA produces educational materials and programming designed to promote informed discussion about patient access to approved therapies and appropriate clinical care. IfPA was established in 2012 by the leadership of the Alliance for Patient Access, a national network of more than 800 physician advocates committed to patient access. IfPA is a 501(c)(3) public charity non-profit organization.
Feedback on Draft Report
The ICER report correctly emphasizes many of the health problems associated with atopic dermatitis, however, several methodological assumptions and decisions that were made in producing the report raise concerns from a patient perspective.
1. “Data availability challenges” leave the report’s impact on patients in question.
To begin, we have concerns regarding the timing of the ICER report. Throughout the study, the authors insert a caveat about significant “data availability challenges,” particularly for dupilumab. This caveat was necessary because dupilumab was not available for purchase by patients when the draft analysis was being conducted. It is likely that the lack of data availability has meaningfully impacted the results of the analysis.
For instance, since dupilumab was not yet available on the market, the price of the drug is unknown. The ICER report assumes that the drug will cost $30,000, and then performs a sensitivity analysis around this value. Such an assumption may be accurate, but it may be inaccurate.
Therefore, the analysis presents a hypothetical result that may, or may not, be applicable to dupilumab depending upon its final price. Yet the ICER methodology creates a cost-effectiveness value with an implied precision that is clearly inappropriate for a drug that has not yet been sold on the market. Moreover, the impact of this report on patient access if dupilumab either assumes a higher initial price, or rises over time to reach a higher price, than $30,000 remains unclear.
2. “Data availability challenges” on long-term impact undermine dupilimab’s net health benefit grade.
Similarly, an important input into ICER’s cost effectiveness analyses is the long-run health impacts from the drug under evaluation. These impacts are unavailable for dupilumab, which leads to arbitrary ratings in the ICER report.
For example, with respect to clinical effectiveness of dupilumab, the ICER report states:
“For adults with moderate-to-severe atopic dermatitis inadequately controlled with topical therapy, or for whom topical therapies are medically inadvisable, we have high certainty that dupilumab provides at least a small net health benefit (“B+”) relative to treatment with emollients with or without continued failed topical treatments. Given limitations of the evidence base, most notably the lack of long-term evidence on the safety of dupilumab, we have moderate certainty that the net health benefit of dupilumab is comparable or better than that provided by cyclosporine, but we have high certainty that dupilumab does not produce a lower net health benefit. Our comparative clinical effectiveness rating for dupilumab versus cyclosporine is therefore “C+”.”
Put differently, the drug is new, therefore, no one has taken it long-term. Since there is no data on long-term impacts, the authors decided that a one letter-grade decrease in the clinical effectiveness of dupilumab was appropriate. The report provides no methodological reason why a one letter-grade decrease is a justifiable penalty. The reduction appears arbitrary at best.
More broadly, and as the above quote indicates, the novelty of dupilumab means that, by definition, the long-run impacts for patients are unknown. Perhaps these long-run impacts are positive – the drug will be well tolerated by patients with few side effects. In such a case, it may have been more appropriate to give dupilumab a one letter grade increase, not a decrease.
Or, perhaps these long-run impacts are negative – the drug will not be well tolerated by patients, or there will be many potential side effects – and a downgrade is appropriate after all. But, even here, whether that should be less, or more, than one letter grade is simply unknowable at this point. In fact, such considerations are precisely why the FDA requires continued drug monitoring of novel therapies after they have been released onto the market.
3. Inattention to subjective factors such as quality of life benefits artificially deflates the value of these therapies to patients with atopic dermatitis.
The ICER report lists several non-medical or non-quantifiable medical benefits to patients who are able to control the symptoms and consequences of atopic dermatitis. These include: unmeasured patient health benefits, impacts on productivity, impact on caregiver burden, impact on public health, lifetime burden from illness, lack of availability of a treatment previously, and interpersonal burdens.
Overall, these benefits represent quality of life improvements that occur when patients can effectively manage their atopic dermatitis. Despite these important benefits, the ICER report then proceeds to declare: “The model used a US health system perspective (i.e., focus on direct medical care costs only).”
The ICER report likely takes this route because “quality of life” factors are difficult to quantify; the report states as much. Yet the omission of these factors will, by definition, artificially lower the benefits that the ICER report expects dupilumab to provide.
Quality of life considerations are always important from a patient perspective; however, such considerations are even more important for diseases such as atopic dermatitis. Many of the condition’s quality of life impacts, such as adverse mental health impacts, physical discomfort, or adverse social impacts, are difficult to quantify. In fact, even diagnosing the severity of atopic dermatitis as mild, moderate, or severe can require subjective considerations. To patients suffering from this disease, however, these subjective assessments are incredibly important.
Therefore, while it is always a mistake to judge the cost-effectiveness of a drug solely on its impact on direct medical costs, the costs from this mistake are compounded for atopic dermatitis. With respect to the ICER report, the omission of these other factors from the cost-effectiveness assessment surely means that the estimated benefits in their model are conservative at best, and more likely to be inappropriately low for most patients.
These benefit impacts are particularly important because, based on the assumed price of $30,000, dupilumab meets ICER’s typical QALY cost thresholds. Therefore, if the assumed price is correct, then the value of dupilumab is much greater than ICER is acknowledging. Consequently, it is vital that the ICER report incorporate reasonable estimates of these subjective costs.
Many behavioral economic studies provide methodologies designed to create cost proxies for subjective assessments. While applying these methodologies will be difficult, and care must be taken to ensure a correct estimate is used, ignoring the costs from subjective benefits create a serious bias against any medicine that is developed to address diseases with harder-to-quantify impacts.
4. Value estimates based on pricing assumptions and incomplete data could ultimately undermine access to treatment for patients with atopic dermatitis.
To the extent that health plans use cost-effectiveness data to determine how accessible a treatment will be for patients, ICER’s determination that dupilumab and crisaborole are cost effective may bode well for atopic dermatitis patients’ ability to access treatment. That access retains an element of uncertainty, however, because of the tentative nature of the data used in calculating the therapies’ value – in particular, the cost and long-term effectiveness of dupilumab.
Consider patients who may soon begin receiving and benefitting from dupilumab for their atopic dermatitis. Should the treatment’s price rise above ICER’s estimate, will health plan coverage for the treatment dissipate? Likewise, if long-term impact data becomes available and drives down ICER’s net health benefit grade, already artificially low, will the new data negate the therapy’s calculated cost effectiveness, jeopardizing health plan coverage?
Tentative findings are vulnerable to reversal, leaving patients who find stable treatment with dupilumab at risk of later losing access or facing non-medical switching attempts by their health plans.
For the above reasons, we have reservations regarding how the ICER report may impact patient access to appropriate treatment for atopic dermatitis. We encourage ICER to revisit the seemingly arbitrary reduction in net health benefit assigned to dupilumab and to also consider how to better incorporate subjective factors related to patient quality of life into its final report.
If IfPA can provide further detail or aid the Institute for Clinical and Economic Review in incorporating any of the above recommendations into its final draft, please contact us at 202-499-4114.