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.

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- the cost of missing a day to generate prescription drug sales and the cost of a day to conduct a clinical trial - are outdated and based on anecdotal evidence.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 Experience in Oncology Clinical Trials.

Background: The drug development industry's focus on cancer-related treatments continues to rise, with narrow patient populations and complex procedures increasing the complexity of oncology protocols at an accelerated rate compared to non-oncology drugs. Tufts Center for the Study of Drug Development utilized data from a study investigating the impact of protocol amendments to compare how oncology clinical trials differ from non-oncology and identify opportunities to optimize performance in oncology clinical trials.

Methods: Sixteen drug development industry companies contributed data from 950 protocols and 2,188 amendments to a study conducted in 2022 investigating protocol amendments.

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.

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.

Insights from a Multi-company Workshop to Apply a Patient Participation Burden Algorithm to Protocol Data.

Background: Utilizing a participation burden algorithm developed in a previous study, Tufts CSDD, in collaboration with ZS, led a workshop among 8 pharmaceutical companies to validate the methodology of benchmarking the participation burden of a set of retrospective protocols and comparing these data to a prospective protocol design.

Methods: Eight participating companies collected data for 66 retrospective protocols and participation burden scores were calculated for each. Data from one prospective protocol was provided and prospective burden scores were compared to mean retrospective protocol burden for each company.

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.

Quantifying Diversity and Representation in Pivotal Trials Leading to Marketing Authorization in Europe.

Background: Following up on a study from 2019, Tufts CSDD collected and analyzed data on demographic disparities and representation in pivotal trials supporting the marketing authorization of novel drugs and biologics approved in Europe between 2007 and 2019.

Methods: Data were collected from products' EPAR, the EUDRACT database, and other publicly available sources, and compared to indication-specific demographic data or a census estimate. In total, data were collected on 446 drugs and 943 pivotal trials.

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.

Protocol Design Variables Highly Correlated with, and Predictive of, Clinical Trial Performance.

Tufts Center for the Study of Drug Development (Tufts CSDD) collected data on trial design elements and clinical trial performance outcomes from 187 protocols provided by 20 companies. 10 design variables were tested for correlations with 11 performance variables, and regression models of each performance variable were tested. Results: Many significant correlations were found (p < .

Evaluating the Feasibility and Validity of a New Tool to Assess Organizational Preparedness and Capabilities to Support Patient Engagement in Drug Development.

Interest in patient-centric initiatives to engage patients as partners in clinical research and inform drug development strategy, planning and execution has increased exponentially during the past decade. Adoption, use, organizational approach and infrastructure supporting patient-centric initiatives, however, varies widely from company to company. The Drug Information Association (DIA) in collaboration with the Tufts Center for the Study of Drug Development (Tufts CSDD) at the Tufts University School of Medicine developed and validated an assessment tool that companies can use to evaluate their organization's patient engagement preparedness and capabilities within the context of industry-wide practices.

Guidelines for Reporting Trial Protocols and Completed Trials Modified Due to the COVID-19 Pandemic and Other Extenuating Circumstances: The CONSERVE 2021 Statement.

Importance: Extenuating circumstances can trigger unplanned changes to randomized trials and introduce methodological, ethical, feasibility, and analytical challenges that can potentially compromise the validity of findings. Numerous randomized trials have required changes in response to the COVID-19 pandemic, but guidance for reporting such modifications is incomplete.

Objective: As a joint extension for the CONSORT and SPIRIT reporting guidelines, CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstances) aims to improve reporting of trial protocols and completed trials that undergo important modifications in response to extenuating circumstances.

Patient Engagement Initiatives in Clinical Trials: Recent Trends and Implications.

Background: As clinical trial protocol designs become more complex and eligible patient populations narrow, it is becoming increasingly difficult to recruit participants and retain them for the duration of the trial. This study surveyed clinical trial participants to learn about the prevalence and impact of new technologies and other supportive solutions designed to improve patient engagement and retention. Patient perceptions of these convenience-enhancing solutions and how they have changed since our last study in 2017 were examined.

The ALPHA Project: Establishing consensus and prioritisation of global community recommendations to address major challenges in lupus diagnosis, care, treatment and research.

The Addressing Lupus Pillars for Health Advancement (ALPHA) Project is a global consensus effort to identify, prioritise and address top barriers in lupus impacting diagnosis, care, treatment and research. To conduct this process, the ALPHA Project convened a multistakeholder Global Advisory Committee (GAC) of lupus experts and collected input from global audiences, including patients. In phase I, the ALPHA Project used expert interviews and a global survey of lupus experts to identify and categorise barriers into three overarching pillars: drug development, clinical care and access to care.

Assessing Patient Participation Burden Based on Protocol Design Characteristics.

Background: Although a number of studies have quantitatively measured investigative site burden to administer increasingly complex protocol designs, robust scholarly research has not been performed to quantify the burden that patients face as participants in clinical trials.

Methods: This paper presents the results of a cross-sectional pilot study conducted by the Tufts Center for the Study of Drug Development and ZS Associates among nearly 600 patients via an online survey conducted between February and March 2019. Respondents rated the perceived burden of 60 commonly administered protocol procedures.