Tufts Center for the Study of Drug Development

About: Tufts Center for the Study of Drug Development is a based out in . It is known for research contribution in the topics: Drug development & Clinical trial. The organization has 78 authors who have published 258 publications receiving 16047 citations.

Economic Impact of a triptan Rx-To-OTC Switch in Six EU Countries

Abstract: Introduction Triptans have been safely and effectively used in the management of migraine for more than fifteen years, and it seems reasonable to wonder what would be the economic impact of moving a specific triptan to OTC availability. The objective of this study was then to examine the economic impact of payer policies of a triptan Rx-to-OTC switch in six EU countries (France, UK, Spain, Italy, Germany and Poland). Methods A decision model was used to model the budgetary impact of a triptan Rx-to-OTC switch from the third-party payer (TPP) and the societal perspectives, using a one-year timeframe. Results From the TPP perspective, it is estimated that the current overall direct spending on the management of migraine attacks across the 6 EU Member States is €582 million annually, and that the savings would reach €75 million (13% of the overall direct economic burden of migraine). From the societal perspective, €86 million annually would be added. Conclusions Given evidence of effectiveness and safety, and given the potential savings, a triptan Rx-to-OTC switch is a reasonable public policy decision.

Off-label use reimbursement.

Abstract: In this study, the authors examine factors underlying payer off-label use reimbursement policies. Updating a study published 14 years ago, presenting the results of the survey of 179 payers administering public (Medicare and Medicaid) pharmacy benefits. The focus is on payers administering pharmacy benefits in the public sector for two reasons: First, transparency; there is a tendency for such payers to reveal more about their decisionmaking processes than payers that exclusively deal with the commercial market. Second, Medicare and Medicaid set the pace in terms of specific policies on off-label use reimbursement, particularly with regard to anti-cancer agents and biologics. The authors investigate the role of primary and secondary sources governing reimbursement of unlabeled indications, including biopharmaceutical compendia, peer-reviewed literature, and clinical practice guidelines. The findings point to the continued variation of off-label use reimbursement policies across payers. Furthermore, the survey data shed light on payer efforts to design off-label use reimbursement strategies, including the use of cost-effectiveness.

Probabilities of success for antibody therapeutics.

Abstract: Probabilities of success (POS) play a key role in determining the distribution of resources by both investors and the pharmaceutical industry. Resources such as time, money and personnel are more likely to be directed toward programs in categories with acceptable rates of success. What is considered acceptable may, of course, vary between companies and other decision-makers. With the increased focus on development of antibody therapeutics, it is important for stakeholders to understand the utility, and limitations, of POS values such as cumulative approval success rates and clinical phase transition probabilities. A key point is that cumulative approval success rates are derived from data for only those candidates with known fates (either approved or terminated), but clinical phase transition probability calculations include data on the status of all candidates. POS values for various cohorts of monoclonal antibody (mAb) therapeutics have been reported previously. 1-6 For mAb POS, a key consideration is the source of the protein sequence. Data for humanized and human mAbs must be analyzed separately because, overall, these molecules display improved safety and efficacy profiles compared to murine and chimeric versions. Humanized mAbs comprise the ‘canonical’ cohort because a large number (>150) of these candidates have entered clinical study over the last two decades (1988–2008), and 12 have been approved (Table 1). However, ultimate fates (approval or termination) are known for only about half, and the cumulative approval success rate for the entire cohort of humanized mAbs will only be an estimate until the fates of all the molecules have been decided. The current cumulative approval success rate estimate for humanized mAbs is 17%. 2 It is important to note that time plays an essential role in POS calculations. In general, clinical study and regulatory review periods for therapeutics are lengthy, and mAbs are not exceptional in this regard. The mean (median) for the combination of the clinical and US Food and Drug Administration (FDA) approval phases for 23 mAbs (Table 1) is currently 8 (7) years. This has important implications for POS calculations for mAb cohorts that include high percentages of candidates that have entered clinical study within the past seven or eight years. Candidates that have entered clinical study since 2001 have not had sufficient time, on average, for approval, but might have been terminated for a variety of reasons. This suggests that there is a downward bias in cumulative success rates for cohorts that include candidates that recently entered clinical study. Indeed, the cumulative success rate for humanized mAbs changes dramatically when the cohort is divided into two groups: candidates that entered clinical study during 1988–1996 (n = 30; eight approved) and 1997–2008 (n = 125; two approved). Ultimate fates are known for 87% of the older candidates, and the cumulative success rate for the cohort is 31%. However, ultimate fates are known for only 33% of the newer candidates, and because many have not been in clinical study long enough to accumulate the

A Drug Lag Update

Abstract: IN THE MID-l970s, Wardell’s pioneering drug lag studies revealed a therapeutically significant delay in the introduction of new drugs in the United States compared with the United Kingdom ( 1,2). These and later studies by other investigators demonstrated that the United States consistently lagged behind other industrialized countries in both the rate and timing of new drug introductions. Moreover, the impact of this delay on therapeutic practice in the United States was not offset by a significantly better safety record. Based on these findings, Wardell (3) concluded that the United Kingdom benefited from its less restrictive policies for approving new drugs and from its more developed program of postmarketing surveillance. At Congressional hearings in 1979, Wardell stated: “There is little doubt that for marketed drugs and approved therapeutic indications, the United States lags greatly, in the sense that new drugs are usually available abroad either exclusively or much earlier, and for a wider range of indications” (4). Although initially rejected by the FDA (5,6), the drug lag concept was eventually accepted as fact by policymakers in Concurrently focused on other concerns, such as health care reform, cost containment, and international competitiveness. Moreover, current efforts to standardize international regulatory practices for pharmaceuticals (eg, through the International Conference on Harmonization) and the increased globalization of the drug industry suggest that disparities among countries in the timing and rate of new drug introductions will eventually diminish. Nonetheless, recent reports in the academic literature and the lay press suggest that the drug lag continues to be a critical issue and that delays persist in the availability of important new therapies in the United States. In this report, the current status of the drug lag is examined. The first section reviews studies by the Tufts Center for the Study of Drug Development (CSDD) that show that the United States continues to lag behind other countries in the introduction of new pharmaceutical products. The next section examines recent data focusing on several specific therapeutic areas. The final section assesses the therapeutic implications of the drug lag.

Adverse Drug Reaction Case Safety Practices in Large Biopharmaceutical Organizations from 2007 to 2017: An Industry Survey

Abstract: Drug safety remains a top global public health concern. An increase in the number of data sources available has increased the complexity of pharmacovigilance operations, so the US FDA has created draft guidance focusing on optimizing drug safety data for well-characterized medicines. However, to date, no data demonstrating changes in reports have been presented. This study provided data assessing changes in individual case safety reports (ICSRs) and aggregate reports (ARs) for large biopharmaceutical companies from 2007 to 2017. This study also evaluated current trends on the use of advanced machine and deep learning in order to process all data captured for ICSRs as well as opinions from industry thought leaders on creating a sustainable case-processing operation. Using data captured from Navitas Life Science’s annual pvnet® benchmark, we calculated workload indicators characterizing pharmacovigilance operations for large biopharmaceutical organizations. Workload indicators included the number of ICSRs by organization, the number of ARs, and the number and types of data sources used. We also conducted structured in-depth interviews with seven biopharmaceutical executives to discover the reasons for changes in workload indicators across time as well as current strategies for increasing efficiencies in drug safety reporting. The median number of ICSRs increased from 84,960 cases in 2007 to over 200,000 cases in 2017; this increase was largely attributable to an increase in both nonserious cases and follow-up cases. Member companies reported using 12 ± 3 data sources for case identification. The number of ARs also increased from a median of 70 reports in 2007 to 258 reports in 2017. To address these increases, 61% of the biopharmaceutical organizations we surveyed planned to adopt machine learning for full ICSR processing; however, as of 2018, none of the organizations surveyed had mechanisms in place. This study demonstrated that pharmacovigilance departments are currently burdened by ever-increasing case volumes. With increased guidance from regulatory agencies, as well as improvements in artificial intelligence and natural language processing, biopharmaceutical organizations must determine the most resource-efficient and sustainable methods to process the growing volume of cases.