The evolution of ICER's review process for new medical interventions and a critical review of economic evaluations (2018-2019): how stakeholders can collaborate with ICER to improve the quality of evidence in ICER's reports.

BACKGROUND: Since its inception in 2006, the Institute for Clinical and Economic Review (ICER) has rapidly gained influence on drug pricing and reimbursement decisions despite historical resistance to the use of cost-effectiveness thresholds in the US health care system. Although patient groups, physicians, and pharmaceutical manufacturers voiced their concerns about the potential negative effects of increased use of ICER's assessments on patient access to innovative medications, there is little guidance and consensus on how the stakeholders should collaborate with ICER to ensure that its reviews reflect the best clinical and economic evidence. OBJECTIVES: To (1) summarize the evolution of ICER's evaluation procedure, scope, and topics; (2) evaluate the effectiveness of stakeholder engagement approaches; and (3) inform stakeholders of their potential role in collaborating with ICER in estimating the cost-effectiveness of new interventions. METHODS: Publicly available ICER evaluations from 2008 to 2019 were systematically reviewed. Changes in evaluation procedures, scope, and topics were summarized. For evaluations that occurred in 2018 (n = 12) and 2019 (n = 8), key characteristics were extracted from 172 letters documenting interactions between ICER and all stakeholders who provided comments to draft reports. Stakeholder suggestions were analyzed in terms of their effectiveness indicated by ICER's reconsideration of its original cost-effectiveness analysis approach. RESULTS: The number of ICER evaluations increased consistently from 2 to 12 per year between 2008 and 2018 but declined to 8 in 2019. Stakeholder opportunity to engage with ICER increased from 1 to 3 per evaluation between 2008 and 2015. ICER initially focused on reviewing general treatment strategies but shifted its focus to specific pharmaceuticals and medical devices in 2014. In 2018 and 2019, 30% of 172 stakeholder letters resulted in a revision in the base-case analysis (49 comments in 2018, 23 in 2019); nearly half of comments in these letters included specific alternative data or a published article to rationalize recommendations. Other common types of suggestions that resulted in ICER's base-case analysis revisions included comments relating to inconsistent methods used to derive model inputs across different treatments (12/49 in 2018, 5/23 in 2019); clinical justifications (12/49 in 2018, 0/23 in 2019); and justifications based on patient perspectives (1/49 in 2018, 5/23 in 2019). These revisions rarely affected ICER's conclusions on the cost-effectiveness of evaluated interventions. Among the 20 assessments that involved 172 stakeholder engagements in 2018 and 2019, only 2% (n = 3) of the engagements (all from 2018) were associated with a change in the cost-effectiveness conclusion. CONCLUSIONS: Between 2018 and 2019, stakeholders leveraged ICER evaluations as opportunities to promote dialogue for better understanding of the value of technologies. Actionable, evidence-based recommendations were accepted more often than other recommendations. DISCLOSURES: No outside funding supported this study. The authors have no conflicts of interest to disclose. Findings from this study were presented as a poster at Virtual ISPOR, May 17-20, 2021.

Correction to: Expected Budget Impact and Health Outcomes of Expanded Use of Vagus Nerve Stimulation Therapy for Drug-Resistant Epilepsy.

The article "Expected Budget Impact and Health Outcomes of Expanded Use of Vagus Nerve Stimulation Therapy for Drug-Resistant Epilepsy", written by Molly F. Purser, Deirdre M. Mladsi, Alan Beckman, Francesca Barion, John Forsey was originally published electronically on the publisher's internet portal (currently SpringerLink) on August 24, 2018 without open access.

Expected Budget Impact and Health Outcomes of Expanded Use of Vagus Nerve Stimulation Therapy for Drug-Resistant Epilepsy.

INTRODUCTION: The objective was to estimate, from the perspective of a managed care organization in the United States, the budget impact and effect on health outcomes of expanded use of vagus nerve stimulation [VNS (VNS Therapy®)] among patients aged ≥ 12 years with drug-resistant epilepsy (DRE) with partial-onset seizures. METHODS: An Excel model was developed to compare the costs of continued anti-epileptic drug (AED) treatment with the costs of VNS plus AED treatment. The number of people eligible for VNS was estimated using published prevalence data and an estimate of the percentage of eligible patients currently without VNS. Costs included VNS device, placement, programming, and battery changes; adverse events associated with VNS (cough, voice alteration, device removal resulting from surgical site infection); AEDs; and seizure-related costs affected by seizure frequency, which affects resource utilization (i.e., hospitalizations, emergency department visits, neurologist visits). To estimate the potential savings with VNS due to a reduction in seizure frequency, the budget impact model uses the results of an underlying Markov model to estimate seizure-related costs by seizure frequency. Transitions occurred among four health states, defined by number of seizures per month (i.e., seizure-free, ≤ 1, > 1 to < 10, ≥ 10) on a 3-month cycle based on published clinical trials and registry data. RESULTS: VNS resulted in an estimated net cost savings, on average, over 5 years, due to the expected reduction in seizure frequency. The initial cost of the VNS device, placement, and programming was estimated to be offset 1.7 years after VNS device placement. Reductions in hospitalizations were the main contributor to the cost savings with VNS. CONCLUSIONS: VNS is a proven intervention that offers a long-term solution for patients with DRE by reducing seizure frequency, which leads to lower resource utilization and lower costs. FUNDING: LivaNova PLC.

Relationship between diclofenac dose and risk of gastrointestinal and cardiovascular events: meta-regression based on two systematic literature reviews.

BACKGROUND: NSAIDs are associated with risks of gastrointestinal (GI) and cardiovascular (CV) toxicities. It has been reported that the risks of GI and CV events are dose related, resulting in guidance explicitly emphasizing the use of NSAIDs at the lowest effective dose for the shortest duration. To understand the potential benefits of using lower doses of diclofenac, a more detailed understanding of the relationship of diclofenac dose and the risks of GI and CV events is required. OBJECTIVE: The objective of this study was to extend previous research quantifying the NSAID dose-toxicity relationship by modeling dose as a continuous measure, allowing for an assessment of the risks of major GI and CV events for patients taking specific diclofenac doses compared with NSAID nonusers. METHODS: We used studies identified in 2 recently published systematic reviews of observational studies that examined the risks of major GI and CV events associated with the use of oral NSAIDs. We developed meta-regression models, considering dose as a continuous measure, to estimate the risks of major GI and CV events for different daily doses of conventional oral diclofenac relative to nonuse of NSAIDs. RESULTS: Seven of the 59 GI publications, contributing 11 dose-specific risk ratio observations, and 12 of the 51 CV studies, contributing 21 dose-specific risk ratio observations, were eligible for inclusion in the meta-regression. The models indicated positive linear relationships between diclofenac dose and the relative risks of major GI and CV events for the range of doses examined. CONCLUSIONS: To our knowledge, this is the first study to quantify and aggregate the continuous relationship between the risk of GI or CV events and the dosage of an NSAID. With the recent availability of new low doses of diclofenac, the models may be used to estimate the potential reduction in risk of adverse events at these doses.

Pharmacy cost evaluation of risperidone, olanzapine, and quetiapine for the treatment of schizophrenia in acute care inpatient settings.

OBJECTIVE: This study examines total pharmacy cost and usage patterns of schizophrenic patients in acute mental health inpatient settings for three atypical antipsychotics -- risperidone, olanzapine, and quetiapine. Despite the readily available unit cost information for drugs, actual pharmacy costs may deviate significantly from 'labeled costs'. Recent research findings indicate the need for more robust evaluation of such pharmacy costs. RESEARCH DESIGN AND METHODS: This study used data from non-randomized inpatient retrospective charts from three acute care inpatient mental health facilities. The final pooled sample included 327 patients, of which 120 received risperidone, 153 received olanzapine, and 54 received quetiapine. Medication cost was defined as the average wholesale price (AWP) as listed in the 2001 'Red Book'. Propensity scoring methodology and multinomial regression were employed to reduce treatment selection bias. RESULTS: The observed mean daily antipsychotic drug doses were 4.45 mg (SD 2.44) for risperidone, 14.04 mg (SD 5.55) for olanzapine, and 350.33 mg (SD 228.24) for quetiapine. The corresponding mean daily drug costs were $7.66(SD $4.20) for risperidone, $8.11 (SD $5.29) for quetiapine and, $12.10 (SD $4.79) for olanzepine. Numbers adjusted for treatment selection bias show that the average daily total pharmacy cost of risperidone was $4.35 lower than olanzapine (p < 0.001) and $1.41 lower than quetiapine (p = 0.38). The adjusted average daily pharmacy cost of olanzapine was $4.02 higher than quetiapine (p < 0.001). After statistical adjustment there were no significant differences between study drugs in terms of length of stay or patient functioning. CONCLUSION: This study provides the first US comparison of medication utilization patterns and pharmacy costs for olanzapine, risperidone, and quetiapine administered in acute mental health care inpatient settings. While this study did not estimate the full economic value of the three antipsychotics in these inpatient settings, it demonstrated that the mean daily costs for risperidone were lower than the mean daily costs for olanzapine (p < 0.001) and quetiapine although the later difference was not statistically significant (p = 0.38).