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.

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.

Correction to: Adverse Drug Reaction Case Safety Practices in Large Biopharmaceutical Organizations from 2007 to 2017: An Industry Survey.

The correct name of the second author should be "Moritz Fehrle", and not "Mortiz Fehrle" as given in the original publication of the article.

Assessing Outsourcing Oversight Practices and Performance.

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 survey examining organizational use of clinical development outsourcing was distributed between February and April 2018. Responses from a total of 88 individuals were included in the final analysis.

Measuring the Impact of Patient Engagement and Patient Centricity in Clinical Research and Development.

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 patients have not been determined.

Methods: The Drug Information Association (DIA), the Tufts Center for the Study of Drug Development (Tufts CSDD), and 17 other stakeholder organizations collaborated on a study to (1) quantify and define patient-centric initiatives (PCIs) utilized in clinical research and development and (2) to define evidence-based metrics and performance indicators that demonstrate return on engagement (ROE) of specific PCIs.

Reflections on the Evolution of Patient Engagement in Drug Development.

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.

Adverse Drug Reaction Case Safety Practices in Large Biopharmaceutical Organizations from 2007 to 2017: An Industry Survey.

Introduction: 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.

Development Times and Approval Success Rates for Drugs to Treat Infectious Diseases.

We gathered data from three pipeline databases and other public sources on development stage and clinical trial metrics for 1,914 investigational drugs, biologics, and vaccines and 2,769 clinical trials intended to treat a wide variety of infectious diseases. We included new molecular entities (NMEs), new formulations, and new combinations. Clinical trial times decreased from 2000-2008 to 2009-2017, varied by disease class, and were longer for trials with more subjects or more sites.

Global consensus building and prioritisation of fundamental lupus challenges: the ALPHA project.

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.