Amgen Response to Washington State Health Technology Assessment (HTA) Program's Draft Evidence Report on the Treatment of Chronic Migraines and Chronic Tension-type Headache

Amgen appreciates the opportunity to comment on the Washington State Health Technology Assessment (HTA) program’s Draft Evidence Report on the treatment of chronic migraines and chronic tension-type headache.

Migraine is a serious disease with real costs to patients, families, employers and the healthcare system. Better preventive options are needed for the 3.5 million people who are currently seeking prevention for their frequent migraine. ^1,2 Approximately 80 percent of these people who start a preventive therapy discontinue within a year, due to intolerable side effects and lack of efficacy. ^3,4 As one of the world’s leading biotechnology companies, Amgen develops medicines that meet important unmet medical needs, including preventive options for people with both chronic and episodic migraine.

We have therefore reviewed with great interest the draft evidence report, “Treatment of chronic migraine and chronic tension-type headache,” published for comment by the HTA Program of the Washington State Health Care Authority on March 6, 2017.

We recognize that the HTA remit encompasses medical devices, procedures and tests, not pharmacological products, and that the draft report accordingly focuses on the treatment of chronic migraine and chronic tension-type headache with OnabotulinumtoxinA, trigger point injections, transcranial magnetic stimulation, manual therapies and acupuncture. Despite not having a pharmacological intervention included in the assessment, we would like to comment on the draft report for the following reasons:

• The treatment of migraine is multimodal and multidisciplinary. Clinicians consider a range of treatment options and frequently switch patients between alternative treatment options.
• Amgen is committed to having an ongoing dialogue with patients, providers, payers, policymakers and regulators to find ways to stimulate innovation of all types, while also alleviating the financial and societal burden of some of the world’s most serious diseases. We therefore seek to engage constructively on the overall approach of HTA initiatives.
• The draft report explains, “Migraine management generally focuses on pharmacological therapy. In chronic headache disorders, including chronic tension-type headache (CTTH) and chronic migraine (CM), the focus of treatment is on preventative measures.” Amgen recognizes that this is an area of high unmet need for people with migraine.

Specifically, we provide comments on the overall approach to HTAs, the cost of disease for headache disorders including migraine, and additional outcomes that should be evaluated.

Overall Approach

Given the stakes for patients, Amgen believes that all economic reviews on the value of medicines should aim to achieve the highest level of transparency, strive for very broad stakeholder engagement, and place scientific rigor and patient interests at the center of the analyses. We believe that a thorough and balanced technology assessment should rely on direct data from rigorous comparative trials when available, calibrated and adjusted for real world application in the heterogeneous markets and treatment settings where the technologies are expected to be used.

Amgen therefore applauds the HTA program for its systematic review of the literature based on transparent inclusion/exclusion criteria and its reporting, with rigorous evaluation of each included study’s results. For example, the review of chronic migraine cost-effectiveness studies provides the weaknesses of each study evaluated in the HTA and notes when the source is from a study with pooled data. However, the draft report failed to note certain instances where validated study data were not included (see the bulleted list under Cost of Disease section for details). A more thorough HTA needs to evaluate all strengths and weaknesses of the economic studies included in the assessment. Finally, it is imperative for a robust HTA to integrate real-world observational evidence in addition to results from randomized control trials in order to capture and model the broad impact of a disease on patients and society in the setting of actual practice.

Cost of Disease

Often HTAs only view the cost of disease from a narrow silo or focus on the short-term financial or budget impact of paying for interventions by estimating direct-cost offsets – i.e. the net financial result of replacing one intervention with another. It is imperative for the scientific rigor of any HTA to evaluate the overall burden and cost of disease holistically and not just the cost of the interventions to create a sustainable health care system. In addition, it is essential to consider the inefficiencies associated with migraine-care delivery and how some of these inefficiencies may be rectified by the use of a more innovative therapy.

To its credit, this HTA does acknowledge the broad societal impact of headache disorders, by noting:

“Headache disorders are associated with substantial impact on the physical, psychological, and social well-being of patients, in addition to having substantial healthcare costs. They are a leading cause of disability and diminished quality of life, making them one of the most common reasons for patient visits in primary care and neurology settings and emergency department visits.” (p. 1)

The HTA also cites several studies estimating indirect costs of migraines, primarily due to reduced work productivity (presenteeism) and missed workdays (absenteeism). However, the systematic review has identified only clinical and cost-effectiveness studies and fails to include recent studies that have further validated the significant indirect costs associated with episodic migraine and CM:

• Migraine patients incur significantly higher indirect costs (absenteeism, short-term disability, and long-term disability costs) than matched non-migraine patients ($11,294 vs $8,945)⁵
• Migraine patients are more likely to have short- and long-term disability claims, and incur ~$1,300 higher per patient disability-related costs than non-migraine patients.⁶
• The indirect economic burden (absenteeism and presenteeism) of migraine is estimated to be ~$13Bn in the US, costing employers up to $4K and $13K per year for episodic and chronic migraine sufferers, respectively.⁷

In addition, a 2017 systematic review of 28 studies found that presenteeism costs are rarely included in full economic evaluations, although the impact of presenteeism in the workplace and society is high. With respect to migraine, Kigozi et al observed:

“Presenteeism, from this review, appears to contribute significantly to productivity costs (or savings) and overall total costs of certain disease areas such as musculoskeletal pain, migraine, and mental health–related disorders. Economic evaluation recommendations in these disease conditions that do not include estimates of presenteeism may result in less than optimal resource allocation decisions from a societal perspective.”⁸

In light of this important information, the HTA could demonstrate the public employee impact of migraine on indirect costs in the State of Washington, similar to data presented for the direct costs relating to the assessed interventions. Sorting Public Employees Benefit Board (PEBB) data using well-known national migraine epidemiology should produce a very compelling picture of this impact.

Insight into the probable results of such an analysis is apparent from publicly available information on the 61,000 employees of the State of Washington’s executive branch. Migraine is prevalent among women, veterans, and people aged 25 to 55 years, each of which account, respectively, for 52.5%, 9.2%, and 49% of the employee population. ^{9,10,11,12,13,14}

We understand the state is developing new employee-engagement workplace-culture measures for a modern work environment and employee safety and wellness. Given the likely greater-than-average prevalence of migraine among state employees, the Washington State Health Care Authority may consider recommending migraine management programs. Amgen would like to recommend a multifaceted migraine management program that was successfully implemented by American Express for its employees. Results from this program showed that employees were able to mitigate their migraine burden, although the program did not prevent migraines.¹⁵

Outcomes

Finally, additional outcomes pertaining to this disease need to be evaluated. Identifying the right interventions for appropriate patients is an important consideration in assessing outcomes of migraine therapy. For example, not all adults affected by migraine are eligible for preventive medication according to medical guidelines.¹⁶ Of these patients, approximately 3.5 million currently take preventive treatment.^{17, 18} It’s also important to note that there is an unmet need to be addressed. Specifically, up to 80 percent of people with migraine who start a preventive therapy discontinue within a year, due to intolerable side effects and lack of efficacy.^19,20

Summary

In closing, we have noted that some HTAs inappropriately fall into a narrow silo or focus on the short-term financial or budget impact of paying for interventions. Often, this involves estimating direct cost offsets – i.e. the net financial result of replacing one intervention with another. Yet, in order to create a sustainable health care system, it is important to look holistically at the burden and overall cost of disease—not just the cost of the interventions. Therefore, it is crucial that HTAs have a long-term view and be focused on the societal perspective, which is consistent with the recently updated recommendations for cost-effectiveness analyses from the Second Panel on Cost-Effectiveness in Health and Medicine.²¹ To its credit, HTA acknowledges the broad societal impact of headache disorders, including chronic migraine. However, a more thorough analysis of real-world evidence, cost of the disease, and additional health-related outcomes would provide a more complete assessment of the significant burden of migraine and the high unmet medical need.

Thank you for the opportunity to comment.