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.

Discrimination experienced by Asian Canadian and Asian American health care workers during the COVID-19 pandemic: a qualitative study.

Background: Asian Canadians and Asian Americans face COVID-19-related discrimination. The objective of this qualitative study was to explore the experiences of Asian health care workers dealing with discrimination, with a focus on racial micro-agressions, in Canada and the United States during the COVID-19 pandemic.

Methods: We adopted a qualitative descriptive approach.

A Useful and Sustainable Role for N-of-1 Trials in the Healthcare Ecosystem.

Clinicians and patients often try a treatment for an initial period to inform longer-term therapeutic decisions. A more rigorous approach involves N-of-1 trials. In these single-patient crossover trials, typically conducted in patients with chronic conditions, individual patients are given candidate treatments in a double-blinded, random sequence of alternating periods to determine the most effective treatment for that patient.

Enhancing the Measure of Participation Burden in Protocol Design to Incorporate Logistics, Lifestyle, and Demographic Characteristics.

Background: Growing interest in improving patient participation convenience and the feasible execution of clinical trials has increased demand for new approaches to leverage patient input in the protocol design process.

Methods: This study builds on prior work conducted by the Tufts Center for the Study of Drug Development in collaboration with ZS. A comprehensive participant burden algorithm based on protocol procedures, participation requirements and lifestyle preferences was developed and tested.

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.

A Survey of Survival Outcomes for Targeted Cancer Drugs Approved by the US Food and Drug Administration.

Background: The last two decades have witnessed the vigorous development of targeted cancer drugs and the potent therapeutic effects of these drugs have been validated by various true and surrogate end points. Overall survival (OS) and progression-free survival (PFS) outcomes were two important end points used in targeted cancer drugs clinical trials but investigation on which was rare as a consequence of inherent heterogeneity and complexity. Here, we present the review and analysis of OS and PFS outcomes of all targeted cancer drugs approved by the U.

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.

Benchmarking the Vendor Qualification Process.

The vendor qualification assessment (VQA) process is regarded as expensive and time consuming but there is no quantitative data characterizing and benchmarking this process. The Tufts Center for the Study of Drug Development (Tufts CSDD)-in collaboration with the Avoca Group and 13 pharmaceutical, biotechnology and contract research organizations-conducted a survey of 120 unique companies to gather baseline data. The study results confirm that companies are investing substantial time and resources to support a high and growing volume of vendor qualifications and re-qualifications each year.

Assessing the Scope and Predictors of Intentional Dose Non-adherence in Clinical Trials.

Background: Although there is broad agreement that the accurate estimation of non-adherence rates in clinical trials is essential to determining the dose-response relationship, treatment safety and efficacy effects, no accurate estimates have ever been produced.

Methods: This study used a novel platform combining artificial intelligence and virtual patient monitoring to identify and quantify the scope of unreported intentional non-adherence in clinical trials of new medical therapies. Nearly 260,000 observations were drawn from a convenience sample of 2976 study volunteers participating in 23 clinical trials of psychiatric, neurological and neuromuscular diseases.

Establishing Consensus Understanding of the Barriers to Drug Development in Lupus.

Objective: Due to the extreme heterogeneity of lupus and the lack of consensus among stakeholders, pharmaceutical and biotechnology companies have had limited success in developing treatments for lupus. For this reason, the Lupus Foundation of America (LFA), researchers at the Center for the Study of Drug Development at Tufts University School of Medicine (Tufts CSDD) and an advisory committee of 13 international lupus experts collaborated to launch the Addressing Lupus Pillars for Health Advancement (ALPHA) project.

Methods: To inform the ALPHA project, 17 in-depth interviews among lupus experts and a global survey among lupus drug development and clinical care professionals was conducted to identify, characterize, and prioritize fundamental barriers and validate findings.

Assessing Participation Burden in Clinical Trials: Introducing the Patient Friction Coefficient.

Protocol design complexity, and associated study volunteer burden, negatively impact patient recruitment and retention as well as overall research and development productivity. Complex protocols reduce the willingness of potential clinical trial participants to enroll and reduce retention rates. There have been few systematic assessments of protocol design characteristics to determine the burden placed on study volunteers, although such an assessment would offer a compelling opportunity to optimize trial designs and improve recruitment and retention performance.

Quantifying Patient Subpopulation Disparities in New Drugs and Biologics Approved Between 2007 and 2017.

Background: Tufts CSDD conducted a study to quantify the magnitude of participant subgroup demographic disparities in industry-funded pivotal trials and establish baseline participant diversity measures.

Methods: Eleven years of data on pivotal trials of all novel drugs and biologics approved between 2007 and 2017 (n = 341 drugs and n = 757 pivotal trials) was compiled and analyzed.

Results: The availability of reported participant demographic subgroup data was poor-most notably participant ethnicity with 63% of pivotal trials supporting all approved treatments missing data.

Benchmarking Patient Recruitment and Retention Practices.

Patient recruitment and retention continue to present challenges in conducting clinical trials. The objectives of the study were to benchmark patient recruitment and retention practices across recent global clinical trials from a working group of biopharmaceutical companies and to re-visit the results from an earlier study published 7 years ago. The data collection focused on patient and site enrollment metrics and recruitment and retention tactics used for studies.

The Financial Benefits of Faster Development Times: Integrated Formulation Development, Real-Time Manufacturing, and Clinical Testing.

Purpose: Faster drug development times get new therapies to patients sooner and financially benefit drug developers by shortening the time between investment and returns and increasing the time on the market with intellectual property protection. The result is enhanced incentives to innovate. We provide a real-world example of the financial gains from quicker development using recent estimates of drug development costs, returns, and estimates of time reductions from an alternative early-stage drug development paradigm.