Economic Aspects of Reimbursement of Drugs for Rare Diseases

The reimbursement of drugs that treat rare diseases, also known as orphan drugs, have been the topic of much debate in the last few years presenting a problem to decision makers who are challenged by increasing drug budgets. This thesis covers three main objectives: 1. Are the Incremental Cost Effectiveness Ratios (ICERs) for rare diseases different from ICERs for non-rare diseases? Although it is believed that ICERs for drugs assessing rare diseases are higher than those of drugs assessing common diseases, no studies to date have formally examined the evidence for this belief. Our objective in this chapter was to assess whether there are differences in ICERs for rare and common cancers using published data. 2. What is the estimated cost of drug development for orphan drugs? Research and Development (R) costs associated with orphan drug development have not been well characterized in the published literature. The objective of this chapter was to identify the differences in clinical trial characteristics between orphan and non-orphan drugs and use that information to estimate the clinical R costs for both groups using publicly available data. 3. What country-specific economic and institutional factors can explain the variability in the reimbursement of orphan drugs in OECD (Organization for Economic Co-operation and Development) countries? It is known that there are differences in the approval and access of drugs across countries. Country-specific factors that lead to these variances have not been studied for orphan drugs. This chapter aims to better understand the differences in the approvals, launch and reimbursement of orphan drugs among 20 OECD countries and determine which economic and institutional factors can explain these differences. The results from these three chapters shed light on three different aspects of reimbursement of orphan drugs including cost-effectiveness, cost of drug development and access to orphan drugs. This research can be essential when developing orphan drug related policies across the world.Ph.D

Natural attack rate of influenza in unvaccinated children and adults: a meta-regression analysis

Abstract Background The natural (i.e. unvaccinated population) attack rate of an infectious disease is an important parameter required for understanding disease transmission. As such, it is an input parameter in infectious disease mathematical models. Influenza is an infectious disease that poses a major health concern worldwide and the natural attack rate of this disease is crucial in determining the effectiveness and cost-effectiveness of public health interventions and informing surveillance program design. We estimated age-stratified, strain-specific natural attack rates of laboratory-confirmed influenza in unvaccinated individuals. Methods Utilizing an existing systematic review, we calculated the attack rates in the trial placebo arms using a random effects model and a meta-regression analysis (GSK study identifier: 117102). Results This post-hoc analysis included 34 RCTs (Randomized Control Trials) contributing to 47 influenza seasons from 1970 to 2009. Meta-regression analyses showed that age and type of influenza were important covariates. The attack rates (95% CI (Confidence Interval)) in adults for all influenza, type A and type B were 3.50% (2.30%, 4.60%), 2.32% (1.47%, 3.17%) and 0.59% (0.28%, 0.91%) respectively. For children, they were 15.20% (11.40%, 18.90%), 12.27% (8.56%, 15.97%) and 5.50% (3.49%, 7.51%) respectively. Conclusions This analysis demonstrated that unvaccinated children have considerably higher exposure risk than adults and influenza A can cause more disease than influenza B. Moreover, a higher ratio of influenza B:A in children than adults was observed. This study provides a new, stratified and up to-date natural attack rates that can be used in influenza infectious disease models and are consistent with previous published work in the field

Differences in Incremental Cost-Effectiveness Ratios for Common Versus Rare Conditions: A Case from Oncology.

BACKGROUND:Incremental cost-effectiveness ratios (ICERs) are used to assess the value for money of new drugs. Many believe that ICERs for drugs that treat rare diseases are much higher than those of common drugs. Our objective was to compare the proportion of ICERs that are cost effective for rare and common cancers. METHODS:We used the Tufts Medical Center Cost-Effectiveness Analysis (CEA) Registry to identify cost-effectiveness studies of pharmaceutical interventions for cancers. Studies that assessed FDA-approved 'orphan drugs' were categorized as assessing rare cancers. The proportion of common and rare cancer drugs that were cost effective at various ICER thresholds were compared along with study characteristics. Logistic regressions were conducted to assess important predictors of cost effectiveness. RESULTS:We identified 303 studies that reported 701 ICERs. Seventy nine percent (n = 240) of studies evaluated drugs for common cancers. At a threshold of US$50,000/QALY, 58$100,000/QALY, 74% (n = 409) of ICERs for common cancers and 78% (n = 115) of ICERs for rare cancers were cost effective (p = 0.35). Results from the logistic regressions demonstrated that rarity was not a statistically significant predictor of cost effectiveness at both thresholds with publication year, study sponsorship, and cancer type as covariates. CONCLUSIONS:The proportion of ICERs that were cost effective at both thresholds does not appear to be significantly different between the two groups. Rarity is not statistically significantly associated with cost effectiveness, even when adjusted for important covariates

Estimating the clinical cost of drug development for orphan versus non-orphan drugs

Abstract Background High orphan drug prices have gained the attention of payers and policy makers. These prices may reflect the need to recoup the cost of drug development from a small patient pool. However, estimates of the cost of orphan drug development are sparse. Methods Using publicly available data, we estimated the differences in trial characteristics and clinical development costs with 100 orphan and 100 non-orphan drugs. Results We found that the out-of-pocket clinical costs per approved orphan drug to be $166 million and$291 million (2013 USD) per non-orphan drug. The capitalized clinical costs per approved orphan drug and non-orphan drug were estimated to be $291 million and$412 million respectively. When focusing on new molecular entities only, we found that the capitalized clinical cost per approved orphan drug was half that of a non-orphan drug. Conclusions More discussion is needed to better align on which cost components should be included in research and development costs for pharmaceuticals