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Background: The target product profile (TPP) outlines the desired profile of a target product aimed at a particular disease and is used by companies to plan clinical development. Considering the increasing importance of health technology assessment (HTA) in informing reimbursement decisions, a robust TPP needs to be built to address HTA needs, to guide an integrated evidence generation plan that will support HTA submissions. This study assessed current practices and experiences of companies in building HTA considerations into TPP development.Methods: An opinion survey was designed and conducted in 2019, as a cross-sectional questionnaire consisting of multiple-choice questions. The questionnaire provided a qualitative assessment of companies’ strategies and experiences in building HTA considerations into the TPP. Eligible survey participants were the senior management of Global HTA/Market Access Departments at 18 top international pharmaceutical companies.Results: 11 companies responded to the survey. All companies included HTA requirements in TPP development, but the timing and process varied. The key focus of HTA input related to health problems and treatment pathways, clinical efficacy/effectiveness, and safety. Variance of HTA methods and different value frameworks were identified as a challenge for development plans. Stakeholder engagement, such as HTA scientific advice, was used to pressure test the TPP.Conclusion: This research provides insight into current practice and potential opportunities for value-based drug development. It demonstrates the evolution of the TPP to encompass HTA requirements and suggests that the TPP could have a role as an iterative communication tool for use with HTA agencies to enhance an integrated evidence generation plan.

BackgroundMany challenges in elderly pharmacotherapy are identified, including the use of Potentially Inappropriate Medications (PIMs) which may increase the odds of adverse events, especially in elderly patients with mental health disorders (e. g., behavioral, and psychological symptoms of dementia–BPSD, schizophrenia, bipolar disorder). However, information on the knowledge and practice of healthcare professionals (HCPs) about this topic is still scarce.MethodsA cross-sectional study was undertaken from July-October 2019. An online questionnaire was specifically designed and validated for this study. We sought HCPs (physicians, pharmacists, and nurses) worldwide, using (a) social media, via Facebook, Twitter, and LinkedIn; and (b) email contacts of the research team (convenience sample). Either way participants were asked to share on their social media or via e-mail the questionnaires with other HCPs (snowballing sample). The survey assessed two main domains: knowledge and practice. Knowledge was evaluated by self-report (perceived knowledge by a 5-item Likert confidence scale) and using three clinical cases, scored between 0 and 30 points (each one rated from 0 to 10 points; real knowledge). Barriers in clinical practice were evaluated using a 5-item Likert scale judging practitioners' opinion.ResultsA total of 165 questionnaires were collected. HCPs were mainly female (n = 114; 69.1%), with a mean age of 35.3 ± 11.3 years old. Seventy-two percent (n = 118) were pharmacists, 21.1% (n = 35) were physicians, and 7.3% (n = 12) nurses. There was a weak correlation, albeit significant, between perceived and real knowledge (r = 0.199; p = 0.001). The mean score of the clinical vignettes regarding elderly patients with dementia and bipolar disorder were 4.59 ± 4.08 and 4.86 ± 2.97 points, respectively. Most HCPs were classified as having an intermediate knowledge (n = 100; 60.6%) about medication complexities in the elderly with mental disorders. Most HCPs agreed that lack of time (81.6%; n = 138), lack of education and training on elderly pharmacotherapy (72.2%; n = 122), and lack of tools adapted to daily practice (61.8%; n = 105) were the main barriers.ConclusionsMost of the HCPs felt confident to manage medication complexities in elder patients with mental disorders, but only a minority obtained a good score in the knowledge assessment test. The main barriers identified included structural barriers (tools unfit for practice) and process barriers (time).

Pancreatic cancer has a dismal prognosis and only a few treatment options are available. In the European Union, pancreatic cancer classifies as a rare disease, allowing drug developers to apply for orphan medicinal product (OMP) designation. The aim of this study was to provide more detail on OMPs for pancreatic cancer. All applications for OMP designation submitted to the EMA between 2000 and 2019 were identified. For each medicinal product that received an OMP designation, the mode of drug action, use of protocol assistance, and current life cycle status was determined. Fifty-two medicinal products received an OMP designation. At the time of submission, eighteen OMPs were at the non-clinical and 34 OMPs were at the clinical stage of development. At least fourteen kinds of mode of action were explored in the condition. For eighteen out of 52 OMPs protocol assistance was sought. At the time of data analysis, one OMP received marketing authorisation and 24 OMPs were ongoing in development. Many medicinal products for pancreatic cancer received an OMP designation and the majority of these products was already in the clinical stage of development. Nonetheless, the success rate of OMPs for pancreatic cancer that reach the market is low, and increasing this rate is something to aspire. Fortunately, development is still ongoing for a part of the OMPs, and a few developers are planning to submit a marketing authorisation application in the near future. This however does not guarantee success, as pancreatic cancer remains a difficult disease to treat. Developers are advised to make optimal use of incentives such as protocol assistance, establishing (early) dialogue between regulators and drug developers and to agree on important topics such as clinical trial design.

Background: Fast and adequate platelet inhibition is one of the cornerstones in the treatment of patients with ST-elevation myocardial infarction (STEMI). The aim of this analysis is to examine sex differences in platelet inhibition in the acute treatment of STEMI patients.Methods: Platelet reactivity units (PRU) and ticagrelor plasma concentrations of all patients in the ON-TIME 3 were compared according to sex. All patients were pre-treated with crushed ticagrelor, aspirin and heparin. Both univariable and multivariable analyses were performed.Results: In this sub-analysis of the ON-TIME 3 trial, 195 STEMI patients, of which 58 female patients (29.7%) and 137 male patients (70.3%), were analyzed. PRU-values immediately post-PCI were not different in females [median 135 (IQR 47-228)] compared to males [160 (IQR 40-219), P = 0.92]. Ticagrelor plasma concentrations were higher in the females at the start of primary PCI [141 ng/mL (IQR 25-491) vs. 76 ng/mL (IQR 15-245), P = 0.049] and at 6 hours post-primary PCI [495 ng/mL (IQR 283-661) vs. 321 ng/mL (IQR 196-537), P = 0.001] compared to males. However, immediately post-primary PCI and at 1-hour post-primary PCI no significant differences in ticagrelor concentrations were seen between sexes. In multivariable analysis, sex was significantly associated with ticagrelor concentration (P = 0.04), but not with PRU (P = 0.93).Conclusion: Effective platelet inhibition reached by crushed ticagrelor in STEMI patients was similar in both sexes. Females had similar or even higher ticagrelor plasma concentrations up to 6 hours post-primary PCI compared with males.

The US Food and Drug Administration (FDA) has four facilitated regulatory pathways (FRPs): Fast Track (FT), Breakthrough Therapy (BTD), Priority Review (PR), and Accelerated Approval (AA). Only PR specifies an expedited review timeline (6 months). We sought to determine to what extent the combination of two or more FRPs influenced development and approval times. We developed a "metro map" to illustrate FRP elements and their influence on review times. We assessed 125 new active substances (approved January 2013 to December 2015) 74 of which used one or more FRPs. For these 74, development times ranged from 1,458 (BTD + PR + AA) to 3,515 days (PR). PR alone had a median approval time of 242 days. The most common combination was FT + PR (median approval 292 days, n = 21). The fastest approval times were for PR + FT + BTD + AA (145 days) and PR + BTD + AA (166 days). Our findings support the combination of FRPs for shortening development and review times beyond that provided by PR alone.

Background: Drug shortages are a potential threat to public health. Reliable data on drug shortages is limited. The objective was to examine the extent and nature of potential drug shortages signaled by authorities and pharmacy practice in the Netherlands Materials and Methods: The primary working systems of Dutch authorities (Medicines Evaluation Board and Health and Youth Care Inspectorate) and the archives of pharmacy practice (Royal Dutch Pharmacists Association) from 2012 to 2015 were searched for number, characteristics, overlap, and date of signals on potential drug shortages. Also, the product characteristics of the potential drug shortages were analyzed from the two different sources Results: Authorities detected 2.6 times more signals on potential shortages than pharmacy practice. Only 438 (8%) out of 5,731 potential drug shortages were detected by both authorities and pharmacy practice. Signals were detected later by authorities than by pharmacy practice, especially on potential permanent shortages (median difference -180 days (IQR: -4 to -405 days)). Authorities detected by majority (72%) signals related to permanent shortages with relative overrepresentation of rectal products and anti-infectives for systemic use. In contrast, pharmacy practice detected by majority (71%) signals related to temporary shortages with relative overrepresentation of ocular and cutaneous products, anti-infectives for systemic use, products for sensory organs and dermatologicals. Conclusions: Authorities and pharmacy practice detected different signals on potential drug shortages with little overlap. Combining data from both authorities and pharmacy practice seems to be necessary in order to gain a more complete overview and maximum insight in potential drug shortages at a national level. Moreover, the finding that authorities were informed later than pharmacy practice causes concerns in terms of opportunities for authorities to assist pharmacy practice to find solutions for shortages.