Showing papers by "Tufts Center for the Study of Drug Development published in 2019"
TL;DR: A study examining the adoption and effect of artificial intelligence (AI), such as machine learning, on drug development found that most organizations use AI in some capacity and that it is important to the success of an organization's workforce.
61 citations
TL;DR: The results from the literature review and use cases provide drug development teams with evidence and insights to help facilitate the adoption of specific PCIs within their organization and to help select those initiatives that would provide the highest impact to patients and development organizations.
Abstract: Background:Recently, drug development companies have sought out patient feedback to improve overall drug development. However, characterization of the overall impact and return on engaging with pat...
30 citations
TL;DR: Wide variation exists in clinical trial site and country information for trials with identical NCT numbers suggesting that caution should be used when relying solely on ClinicalTrials.gov to assess the clinical trial landscape.
Abstract: Background:To date, although studies have been conducted to assess compliance with listing clinical trial information, to our knowledge there is nothing in the literature examining the completion a...
17 citations
TL;DR: The author’s opinion on the past and present state of the Patient Engagement movement is presented and ways in which the movement will need to change and evolve if it is to become viable and standard practice in drug development are discussed.
Abstract: This article presents the author’s opinion on the past and present state of the Patient Engagement movement and discusses ways in which the movement will need to change and evolve if it is to become viable and standard practice in drug development. For most of the past decade, drug development sponsors—both government-funded and industry-funded research—have been aspirational in their support of Patient Engagement initiatives. New frameworks and guidelines have been proposed and developed, and a wide variety of initiatives have been planned and piloted. Many factors have facilitated a tentative and experimental posture—these include internal resistance to modifying legacy practices and processes; insufficient funding and staff to implement and manage initiatives; lack of clarity from regulatory and health authorities; and uncertainty around expected impact and return on investment. Recently, research sponsors have begun restructuring their Patient Engagement capabilities and they have been seeking more concrete return on engagement measures. These developments signal that the Patient Engagement movement has entered a new phase, becoming more rigorous as it seeks to balance ethical and moral obligations with scientific and business imperatives.
16 citations
TL;DR: The Addressing Lupus Pillars for Health Advancement (ALPHA) project is the first step in establishing global consensus and developing concrete strategies to address the challenges limiting progress, and provides a framework to generate actionable approaches to the identified high-priority barriers.
Abstract: Objective Lupus is a complex, heterogeneous autoimmune disease that has yet to see significant progress towards more timely diagnosis, improved treatment options for short-term and long-term outcomes, and appropriate access to care. The Addressing Lupus Pillars for Health Advancement (ALPHA) project is the first step in establishing global consensus and developing concrete strategies to address the challenges limiting progress. Methods A Global Advisory Committee of 13 individuals guided the project and began barrier identification. Seventeen expert interviews were conducted to further characterise key barriers. Transcripts were analysed using Nvivo and a codebook was created containing a list of thematic ‘nodes’ (topics) and their descriptions. Findings were used to develop a final survey instrument that was fielded to a diverse, international stakeholder audience to achieve broad consensus. Results Expert interviews identified lupus heterogeneity as the primary barrier hindering advancement. Subsequent barriers were categorised into three areas: (1) Drug development. (2) Clinical care. (3) Access and value. The global survey received 127 completed responses from experts across 20 countries. Respondents identified barriers as high priority including the lack of biomarkers for clinical and drug development use, flawed clinical trial design, lack of access to clinicians familiar with lupus, and obstacles to effective management of lupus due to social determinants of care. Respondents also identified 30 autoimmune conditions that may be lupus-related based on overlapping features, shared autoantibodies and pathophysiology. Conclusions ALPHA is a comprehensive initiative to identify and prioritise the continuum of challenges facing people with lupus by engaging a global audience of lupus experts. It also explored views on lupus as a spectrum of related diseases. Conclusions from this effort provide a framework to generate actionable approaches to the identified high-priority barriers.
16 citations
TL;DR: It is demonstrated that pharmacovigilance departments are currently burdened by ever-increasing case volumes and biopharmaceutical organizations must determine the most resource-efficient and sustainable methods to process the growing volume of cases.
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.
14 citations
TL;DR: In planning EE2 trials, each stakeholder's current and future needs, incentives, and perspective must be considered, and although challenging, the ultimate benefits to stakeholders, the health system, and the public should justify this effort.
Abstract: Efficacy trials, designed to gain regulatory marketing approval, evaluate drugs in optimally selected patients under advantageous conditions for relatively short time periods. Effectiveness trials, designed to evaluate use in usual practice, assess treatments among more typical patients in real-world conditions with longer follow-up periods. In "efficacy-to-effectiveness (E2E) trials," if the initial efficacy trial component is positive, the trial seamlessly transitions to an effectiveness trial component to efficiently yield both types of evidence. Yet more time could be saved by simultaneously addressing efficacy and effectiveness in an "efficacy and effectiveness too (EE2) trial." Additionally, hybrids of the E2E and EE2 approaches with differing degrees of overlap of the two components could allow flexibility for specific drug development needs. In planning EE2 trials, each stakeholder's current and future needs, incentives, and perspective must be considered. Although challenging, the ultimate benefits to stakeholders, the health system, and the public should justify this effort.
13 citations
TL;DR: This review will provide input on approaches that are needed to continue to advance pediatric drug development with an emphasis on rare diseases and the impact of existing regulations and the likely trajectory of future pediatric drugdevelopment efforts after nearly 2 decades of regulatory incentives.
Abstract: Surveys evaluating industry experience with performing pediatric studies under the Best Pharmaceutical for Children Act (BPCA) and Pediatric Research Equity Act (PREA) regulatory regime were conducted by Tufts Center for the Study of Drug Development (Tufts CSDD) in 2000, 2006, and 2016. These survey results are being used to assess the future impact of regulatory incentive programs on generating pediatric specific labeling information and development of age-appropriate drug formulations. A second perspective will be provided through the experience and expertise of neonatal/pediatric clinicians and researchers with a focus on the urgent need for the study of new and existing drugs in this vulnerable population (especially with 90% of drugs in neonates still being used off-label). This group will also address the impact of existing regulations and the likely trajectory of future pediatric drug development efforts after nearly 2 decades of regulatory incentives (both mandatory and voluntary). Finally, this review will provide input on approaches that are needed to continue to advance pediatric drug development with an emphasis on rare diseases.
12 citations
TL;DR: Study results indicate that firms are using an average of 6 different applications to support each clinical study and that companies are collecting a range of data types including that from case report forms, lab procedures, pharmacokinetics, biomarker, outcomes assessment, mobile health, and social media.
Abstract: The volume and diversity of data collected to support each clinical study has increased dramatically in response to the rising scope and complexity of global drug development programs. The Tufts Center for the Study of Drug Development conducted an online survey of 257 unique global companies-77% drug development sponsors and 23% contract service providers-to assess clinical data management practices and experiences. Study results indicate that companies are using an average of 6 different applications to support each clinical study and that companies are collecting a range of data types including that from case report forms, lab procedures, pharmacokinetics, biomarker, outcomes assessment, mobile health, and social media. Companies report that the primary electronic data capture (EDC) is capturing traditional data types but not many of the newer ones. Respondents report spending an average of 68.3 days to build and release a study database, 8.1 days between the patient visit and when that patient's data are entered into the EDC system, and 36.3 days on average to lock the database following the last patient last visit. Average cycle time durations are longer and more variable than those observed ten years ago. Subgroup differences (eg, by company size and company type) and factors contributing to data management cycle time and experience are discussed.
12 citations
TL;DR: The diagnostic algorithm (nNO/HSVM+TEM) with parallel testing outperforms algorithms with tests in sequence and can inform the dialogue on the development of evidence-based guidelines for PCD diagnostic testing.
Abstract: Primary Ciliary Dyskinesia (PCD) diagnosis relies on a combination of tests which may include (a) nasal Nitric Oxide (nNO), (b) High Speed Video Microscopy (HSVM) and (c) Transmission Electron Microscopy (TEM). There is variability in the availability of these tests and lack of universal agreement whether diagnostic tests should be performed in sequence or in parallel. We assessed three combinations of tests for PCD diagnosis and estimated net sensitivity and specificity as well as cost-effectiveness (CE) and incremental cost-effectiveness (ICE) ratios. A hypothetical initial population of 1000 referrals (expected 320 PCD patients) was followed through a probabilistic decision analysis model which was created to assess the CE of three diagnostic algorithms (a) nNO + TEM in sequence, (b) nNO + HSVM in sequence and (c) nNO/HSVM in parallel followed, in cases with conflicting results, by confirmatory TEM (nNO/HSVM+TEM). Number of PCD patients identified, CE and ICE ratios were calculated using Monte Carlo simulations. Out of 320 expected PCD patients, 313 were identified by nNO/HSVM+TEM, 274 with nNO + HSVM and 198 with nNO + TEM. The nNO/HSVM+TEM had the highest mean annual cost (€209 K) followed by nNO + TEM (€150 K) and nNO + HSVM (€136 K). The nNO + HSVM algorithm dominated the nNO + TEM algorithm (less costly and more effective). The ICE ratio for nNO/HSVM+TEM was €2.1 K per additional PCD patient identified. The diagnostic algorithm (nNO/HSVM+TEM) with parallel testing outperforms algorithms with tests in sequence. These findings, can inform the dialogue on the development of evidence-based guidelines for PCD diagnostic testing. Future research in understudied aspects of the disease, such as PCD-related quality of life and PCD-associated costs, is needed to help the better implementation of these guidelines across various healthcare systems.
8 citations
TL;DR: The origins of this misalignment in the development and approval of new active substances, with its disproportionate focus on oncology, is discussed and various approaches to address healthcare needs going forward are suggested.
Abstract: A host of challenges confront healthcare authorities worldwide. Topping the list is the demand for innovative new medicines to treat a range of both infectious and non-communicable diseases, while containing spiraling healthcare costs. The challenge is particularly great in therapeutic areas where, despite significant medical need and economic impact, the technical challenges and commercial risk of development serve as disincentives to drug sponsors. These areas include cardiovascular diseases as well as diseases and disorders of the central nervous system. Currently, the development and approval of new active substances, with its disproportionate focus on oncology, is not in alignment with healthcare needs in most geographic regions. In this article, we discuss the origins of this misalignment and suggest various approaches to address healthcare needs going forward.
TL;DR: Several opportunities to improve oversight practices were identified in the study, including increasing executive-level involvement and leveraging technologies to monitor performance, enhance communication, and expand collaboration capabilities.
Abstract: Background:The Tufts Center for the Study of Drug Development conducted a study updating benchmarks on outsourcing model adoption and assessing oversight practices and experience.Methods:An online ...