Drug repurposing for neglected and zoonotic diseases.

Globalization and climate change have intensified the need to address the marginalization of R&D for neglected and zoonotic diseases. We propose that drug repurposing, using enabling technologies such as artificial intelligence, can address this need at a lower cost than de novo R&D processes.

The influence of socioeconomic status on individual attitudes and experience with clinical trials.

Background: Characterizing perceptions of clinical trials among the socioeconomically disadvantaged is necessary for understanding how social determinants of health such as socioeconomic disparities in education and income can affect people's awareness of and exposure to clinical trials METHODS: A survey was distributed in spring 2023 among a survey taking sample stratified by demographic variables to reflect the U.S.

Population: The survey assessed the socioeconomic status of the respondent and related covariates, as well as outcome measures including interest in joining a clinical trial, concerns relating to participation, and whether the respondent had previously been asked to participate.

Assessing the net financial benefits of employing digital endpoints in clinical trials.

In the last few decades, developers of new drugs, biologics, and devices have increasingly leveraged digital health technologies (DHTs) to assess clinical trial digital endpoints. To our knowledge, a comprehensive assessment of the financial net benefits of digital endpoints in clinical trials has not been conducted. We obtained data from the Digital Medicine Society (DiMe) Library of Digital Endpoints and the US clinical trials registry, ClinicalTrials.

Mapping Strategies for Reaching Socioeconomically Disadvantaged Populations in Clinical Trials.

Importance: Socioeconomically disadvantaged patients, such as persons with low income and those with low educational attainment, are less likely to participate in clinical trials than those with higher earnings and higher educational attainment, despite the former being more likely to have chronic medical conditions. Ways to improve the representation of socioeconomically disadvantaged patients in clinical trials deserve attention.

Objective: To examine whether current recruitment and enrollment strategies used by US clinical research sites appropriately include patients from socioeconomically disadvantaged backgrounds.

New Estimates on the Cost of a Delay Day in Drug Development.

Two frequently cited figures by clinical research insiders and observers - the cost of missing a day to generate prescription drug sales and the cost of a day to conduct a clinical trial - are outdated and based on anecdotal evidence. In late 2023, the Tufts Center for the Study of Drug Development conducted empirical research to gather more accurate and granular estimates and to test whether average sales per day have changed over time. 645 drugs launched since 2000, and 409 clinical trial budgets were drawn from commercially available and proprietary data sets and analyzed.

Examining the Association Between DCT Solutions Use and Participant Diversity in Clinical Trials.

Background: Whereas anecdotal reports suggest that the use of decentralized clinical trial (DCT) solutions can improve participant diversity in clinical trials there is no quantitative evidence to support such reports.

Methods: Tufts CSDD conducted this initial study based on data collected from prior research and publicly available data drawn from Clinicaltrials.gov to compare and contrast participant diversity in trials which included various DCT solutions - virtual visits or televisits, home visits, devices or wearables, and the use of local labs.

Benchmarking Site Activation and Patient Enrollment.

Clinical trial conduct poses numerous challenges, many pertaining to patient recruitment. The primary objectives of this study were to update benchmarks on site activation and patient enrollment gathered in previous Tufts CSDD studies and examine current usage of recruitment and retention tactics. The data collection focused on site activation and patient enrollment metrics used for studies.

New Benchmarks on Protocol Amendment Practices, Trends and their Impact on Clinical Trial Performance.

The Tufts Center for the Study of Drug Development (Tufts CSDD) conducted a follow-up study in 2022 to assess trends in protocol amendment experiences and the impact amendments have had on clinical trial performance, particularly during the COVID-19 pandemic. Sixteen pharmaceutical companies and contract research organizations provided data on 950 protocols and 2188 amendments. The results show that, since 2015, the prevalence of protocols with at least one amendment in phases I-IV has increased substantially (from 57 to 76%) and the mean number of amendments per protocol has increased 60% to 3.

Comprehensive Assessment of Risk-Based Quality Management Adoption in Clinical Trials.

Background: Risk-based monitoring (RBM) and risk-based quality management (RBQM) offer a compelling approach to increase efficiency, speed and quality in clinical trials by prioritizing and mitigating risks related to essential safety and efficacy data. Since 2013, the FDA and EMA have encouraged the use of RBM/RBQM, however adoption has been slow with limited understanding of the barriers to adoption.

Methods: The Tufts Center for the Study of Drug Development conducted an online survey among pharmaceutical, biotechnology, and contract research organizations and gathered 206 responses on 32 distinct RBQM practices.

Quantifying Site Burden to Optimize Protocol Performance.

Background: The increase in protocol complexity and the resulting rise in the effort required by investigative sites to implement protocols have been well documented, but existing measures of site burden only offer an incomplete view of the burden experienced by site personnel. The introduction of Decentralized Clinical Trials-trials supported by remote and virtual technologies and services-is expected to impact the burden imposed on sites, but this impact has not yet been systematically measured.

Methods: The Tufts Center for the Study of Drug Development conducted an online survey among clinical research sites worldwide and gathered 355 responses assessing the burden associated with distinct activities and procedures related to the implementation of clinical trial protocols using traditional and decentralized approaches.

A Case Study Assessment on the Rationale for, and Relevance of, Non-Core Protocol Data.

To better understand the nature of Non-Core procedures and derive new insight into protocol simplification and optimization, Tufts CSDD collaborated with the FDA and sponsor companies to assess alignment on the rationale for collecting, and relevance of, Non-Core protocol data. Twelve sponsor companies classified and rated 700 distinct procedures from 19 pivotal trials supporting new drug and biologics approvals. FDA reviewers classified and rated 80 distinct procedures for three of the 19 pivotal trials.

New Benchmarks on Demographic Disparities in Pivotal Trials Supporting FDA-Approved Drugs and Biologics.

Background: A lack of diversity and representation in clinical trials is an established issue in drug development, and the COVID-19 pandemic increased awareness of the problem among the general public. This awareness has led to increased pressure on drug development sponsors, as well as additional attention and regulation from federal bodies, to improve the diversity of clinical trials. This study updates existing baselines regarding demographic disparities, as well as detecting early signs that the situation may be starting to improve.

Is Your Organization's Remote Work Strategy "Working"? Exploring the Impact of Employees' Attitudes Toward Flexible Work Arrangements on Inclusion and Turnover Intention.

The Covid-19 pandemic drastically changed the way people work. This was no exception in the drug development industry, which like other industries has been grappling with the challenge of how to manage the transition back to the office while ensuring that people feel included. To understand what strategies organizations in the drug development industry are adopting and examine their impact on the employee experience, Tufts Center for the Study of Drug Development launched a survey that quantified the different strategies and their effect on work outcomes, including burnout, inclusion, and turnover.

Applying Systems Thinking to Inform Decentralized Clinical Trial Planning and Deployment.

Recently, there has been a growing interest in understanding how decentralized clinical trial (DCT) solutions can mitigate existing challenges in clinical development, particularly participant burden and access, and the collection, management, and quality of clinical data. This paper examines DCT deployments, emphasizing how they are integrated and how they may impact clinical trial oversight, management, and execution. We propose a conceptual framework that employs systems thinking to evaluate the impact on key stakeholders through a reiterative assessment of pain points.

Benchmarking Patient Engagement Capabilities and Preparedness of Drug Development Sponsors.

Consistent implementation and measurement of patient engagement initiatives across the industry have remained aspirational and elusive despite strong interest in adopting patient-centric approaches. One factor contributing to this inertia stems from a lack of standardized implementation of patient engagement activities, which varies widely from company to company, making it difficult to track and measure. Further, empirical evidence mapping the impact of patient engagement capabilities on clinical research outcomes has remained sparse.

Rapid progress in neuroimaging technologies fuels central nervous system translational medicine.

Central nervous system (CNS) drug discovery suffers from high attrition rates; translational neuroscience approaches aiming to reduce these high rates include the use of brain imaging technologies. However, there is a need to better understand what methods are being used and for what diseases and purposes. Our analysis of the literature found that magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT) were the neuroimaging techniques used most often in clinical trials for the most prevalent CNS diseases: Alzheimer's disease (AD), Parkinson's disease (PD), depression, and schizophrenia.

Assessing the Financial Value of Decentralized Clinical Trials.

Background: Deployment of remote and virtual clinical trial methods and technologies, referred to collectively as decentralized clinical trials (DCTs), represents a profound shift in clinical trial practice. To our knowledge, a comprehensive assessment of the financial net benefits of DCTs has not been conducted.

Methods: We developed an expected net present value (eNPV) model of the cash flows for new drug development and commercialization to assess the financial impact of DCTs.

Protocol Design and Performance Benchmarks by Phase and by Oncology and Rare Disease Subgroups.

Background: Benchmark data characterizing protocol design practices and performance informs clinical trial design decisions and serves as important baseline measures for assessing protocol design behaviors and their impact during and post-pandemic.

Methods: Tufts CSDD, in collaboration with a working group of 20 major and mid-sized pharmaceutical companies and CROs, gathered phase I-III data from protocols completed just prior to the start of the global pandemic.

Results: Data for 187 protocols were analyzed to derive benchmarks overall and for two primary subgroups: oncology vs.

Global Investigative Site Personnel Diversity and Its Relationship with Study Participant Diversity.

Background: There is little to no empirical data on the race and ethnicity of the global community of professionals conducting clinical trials funded by pharmaceutical and biotechnology companies and little empirical evidence on the relationship between the race and ethnicity of investigative site personnel and the overall and corresponding diversity of participants enrolled.

Methods: A global online survey conducted in mid-2021 gathered responses from 3462 clinical research professionals representing approximately 3300 distinct investigative sites.

Results: Worldwide, including all research settings, the majority (64%) of investigative site personnel are White, 20% are LatinX, 6% are Black, 7% are Asian and 3% are other races and ethnicities (e.

Benchmarking Protocol Deviations and Their Variation by Major Disease Categories.

Background: Little to no data exist quantifying and benchmarking the magnitude of protocol deviation experience.

Methods: Nearly two-dozen companies provided the Tufts Center for the Study of Drug Development (Tufts CSDD) with data on the design and the performance of 187 protocols.

Results: The results of this working group study show that phase II and III protocols have a mean total of 75 and 119 protocol deviations, respectively, involving nearly one-third of all patients enrolled in each clinical trial.

Strategic, feasibility, economic, and cultural aspects of phase 0 approaches: Is it time to change the drug development process in order to increase productivity?

Research conducted over the past 2 decades has enhanced the validity and expanded the applications of microdosing and other phase 0 approaches in drug development. Phase 0 approaches can accelerate drug development timelines and reduce attrition in clinical development by increasing the quality of candidates entering clinical development and by reducing the time to "go-no-go" decisions. This can be done by adding clinical trial data (both healthy volunteers and patients) to preclinical candidate selection, and by applying methodological and operational advantages that phase 0 have over traditional approaches.