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. This paper discusses the development of the tool, the assessment experience, and implications for further refinement of the assessment process. Specifically, the team conducted an extensive literature review, compiled and analyzed case studies and gathered input from a working group of 18 biopharmaceutical companies. To validate the assessment tool and demonstrate its feasibility, the DIA-CSDD Tufts team conducted a pilot implementation involving onsite and virtual in-depth interviews among 14 biopharmaceutical companies. A subsequent paper will report on the findings from the 14 companies assessed.

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. In phase II, reported here, the GAC developed recommended actionable solutions to address these previously identified barriers through an in-person stakeholder meeting, followed by a two-round scoring process. Recommendations were assessed for feasibility, impact and timeline for implementation (FIT), where potential FIT component values were between 1 and 3 and total scores were between 3 and 9. Higher scores represented higher achievability based on the composite of the three criteria. Simplifying and standardising outcomes measures, including steroid sparing as an outcome (drug development) and defining the lupus spectrum (clinical care) ranked as the highest two priority solutions during the GAC meeting and received high FIT scores (7.67 and 7.44, respectively). Leveraging social media (access to care) received the highest FIT score across all pillars (7.86). Cross-cutting themes of many solutions include leveraging digital technology and applying specific considerations for special populations, including paediatrics. Implementing the recommendations to address key barriers to drug development, clinical care and access to care is essential to improving the quality of life of adults and children with lupus. Multistakeholder collaboration and guidance across existing efforts globally is warranted.

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. The association and relationship between overall patient burden-derived from aggregating mean perceived burden ratings for individual procedures-and performance (eg, screen failure and retention rates, clinical trial cycle times) for a cross-sectional sample of 137 individual protocols was assessed. Descriptive statistics, significance tests, and univariate analyses were performed. RESULTS: Strong positive, statistically significant associations were observed between a composite measure of patient burden and protocol-specific design and performance measures, most notably study visits above the tolerable mean and the study conduct duration from first patient first visit to last patient last visit. CONCLUSIONS: The study results suggest a new and viable approach to optimize protocol design and improve patient engagement.

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. RESULTS: The global survey received 127 responses from experts across 20 countries. Results of the in-depth interviews and the survey findings were consistent. Top barriers to developing new medical treatments for lupus included the lack of a clear definition of the disease with respondents identifying 30 autoimmune conditions that may be lupus-related; lack of predictive biomarkers; flaws in clinical trial designs; and a lack of reliable outcome measures. CONCLUSION: The study findings encourage drug development professionals to validate disease-specific measures and to identify if specific symptoms are caused by lupus. This original research also provides a methodology that can be applied to highly heterogenous diseases where low consensus on diagnosis and treatment exists among drug development and health professionals.

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. The availability of data on participant race and ethnicity did not improve between 2007 and 2017. Participants of Black or of African Descent were the subgroup most highly under-represented. Three times as many participants in this demographic subgroup should have been enrolled in pivotal trials to achieve representation as dictated by disease prevalence rates and population census figures. Although variation was observed between disease conditions, under-representation of Black/African Descent participants occurred in nearly all conditions. Participants from indigenous communities were also highly under-represented. Asian participants were highly over-represented in pivotal trials. Approximately 14% more Hispanic/Latinx participants should have been enrolled in clinical trials to achieve population-proportional representation. CONCLUSIONS: The results suggest that participant demographic disclosure practices are falling short and that insufficient diversity in clinical trials is limiting the value of guidance on medical treatment dosing and response. The study findings supplement the FDA's Drug Trial Snapshot Reports and offer insight into the magnitude of, and trends in, participant demographic subgroup disparities.

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. Clinical approval success rates were higher for this set of diseases than those in the published literature for drugs across all therapeutic categories. NMEs to treat HIV had a success rate (16.0%) that was similar to those for drugs in general, whereas NME success rates for influenza and pneumonia were much higher (48.1% and 50.5%, respectively).

Assessing Biopharmaceutical Company Experience with Patient-centric Initiatives.

PURPOSE: A growing number of biopharmaceutical companies have been implementing patient-centric initiatives (PCIs). The Drug Information Association (DIA) and the Tufts Center for the Study of Drug Development (CSDD) collaborated on a study to gather data on the usage and impact of these PCIs to characterize company experience and impact. METHODS: DIA and Tufts CSDD collaborated with 17 organizations to define PCIs used in clinical research and development and to quantify their use, and to define metrics in use to document impact and return on engagement (ROE) for these PCIs. The study used a mixed methods approach that consisted of an online survey, in-depth interviews, and literature review. FINDINGS: Twenty-two unique companies responded to an on-line survey on the use of 23 PCIs identified by the study working group. PCIs most frequently implemented included patient organization landscape analysis, support of patient advocacy groups, use of patient advisory boards, and use of home nursing networks. Seven additional PCIs were found through a literature search and included in the group of PCIs for which impact measures were assessed. A total of 121 cases of use of the 30 PCIs and associated impact measures and impact data were gathered through literature review, in-depth interviews with the study companies, and in-depth interviews with organizations identified in the literature as having experience with patient engagement in clinical research as well as with patients who had participated in clinical trials. Analysis of the 121 case studies resulted in a list of 666 measures of impact (metrics) in use for 13 of the PCIs. Assessment of overall ROE for these PCIs found that PCIs such as support of patient advocacy groups and use of patient advisory boards indicated the greatest ROE, whereas costlier, more complex PCIs such as digital medicine and gaming indicated relatively low ROE. IMPLICATIONS: Activity around PCIs among the companies studied was widespread, with initiatives more frequently planned and piloted than implemented at the time of this study. Measures of impact have been identified and can be used to assess ROE, providing insights to facilitate the adoption of PCIs of highest impact for patients and biopharmaceutical research organizations.

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. The association and relationship between overall patient burden-derived from aggregating mean perceived burden ratings for individual procedures-and performance (eg, screen failure and retention rates, clinical trial cycle times) for a cross-sectional sample of 137 individual protocols was assessed. Descriptive statistics, significance tests, and univariate analyses were performed. RESULTS: Strong positive, statistically significant associations were observed between a composite measure of patient burden and protocol-specific design and performance measures, most notably study visits above the tolerable mean and the study conduct duration from first patient first visit to last patient last visit. CONCLUSIONS: The study results suggest a new and viable approach to optimize protocol design and improve patient engagement.

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. 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.