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Background: Tufts Center for the Study of Drug Development (Tufts CSDD), in collaboration with 15 pharmaceutical companies and contract research organizations, gathered data on substantial global protocol amendments to better understand how to manage and to reduce the significant unplanned expense and delays associated with major changes to finalized protocol designs. Methods: Data from 836 phase I-IIB/IV protocols were analyzed to understand amendment prevalence. Impact assessments were based on data from 136 randomly selected amendments. Data from 52 protocols were analyzed to derive estimates of the direct cost to implement amendments. Results: Tufts CSDD found that 57% of protocols had at least one substantial amendment, and nearly half (45%) of these amendments were deemed “avoidable.” Phase II and III protocols had a mean number of 2.2 and 2.3 global amendments, respectively. Protocols with one or more global amendments tended to be larger in scope, with longer patient recruitment durations and overall study durations compared with those without a global amendment. Protocols with at least one substantial amendment had fewer actual screened and enrolled patients relative to the original baseline plan than did those protocols without an amendment. The median direct cost to implement a substantial amendment was US$141,000 for a phase II protocol and $535,000 for a phase III protocol. Conclusions: The study findings provide insights into optimizing development planning, protocol design, and clinical trial management practices. [ABSTRACT FROM AUTHOR]

Background: With the pharmaceutical industry’s increased attention on enhancing patient experiences during their participation in clinical trials, the use of mobile nurse (MN) services to support the conduct of clinical trial assessments in the home (or in alternative locations other than in investigational sites) has been gaining momentum. Methods: Because no quantitative data capturing industry-wide practices are available, in July 2014, Tufts Center for the Study of Drug Development and Hoffman-La Roche conducted an online survey to gather data on the prevalence and utilization of MN services in clinical trials taking into account the following factors: industry perceptions of the business model, risks barriers to adoption, vendor landscape, cost, and prospects for future growth. A total of 113 respondents answered the survey, with 53 respondents answering all questions. Results: The use of MN services in clinical trials is an established and growing business practice. Utilization of MN services has so far been most prevalent in North America, followed by Western Europe. Sponsor companies that have adopted this model have done so mainly to improve patient retention and protocol compliance, as well as improve access to rare patients. Most of the companies surveyed work directly with vendors specializing in home nurse services. Experience with vendors was considered favorable in most cases. Conclusions: Building effective partnerships with 1 to 2 vendors is considered a key factor for long-term success. [ABSTRACT FROM AUTHOR]

Background: The Tufts Center for the Study of Drug Development (Tufts CSDD) collaborated with the Clinical Data Interchange Standards Consortium (CDISC) on a joint working group study with 10 participating companies including biopharmaceutical, CROs, and eClinical technology vendors. The objective of the study was to examine current and projected use of eClinical technology and standards across respondent organizations and in clinical studies and to gather perceptions and attitudes about technology and standards adoption. Methods: The Tufts CSDD study examined the use of eClinical technology and CDISC standards through a comprehensive survey combined with analyses of clinical study data among biopharmaceutical companies and contract research organizations. Results: The results suggest increasing use of specific eClinical technology solutions and standards. The barriers to adoption of eClinical trial tools are addressed as well as the benefits of standards adoption. Differences between respondent perceptions and actual study data are examined, and the survey results are compared with those from prior studies. Conclusions: The results of the study indicate that increasing use of standards could translate into improvements in time, costs, and overall approval rates. The study also observed an uptake in the use of eClinical technologies that could potentially create efficiencies and streamline operational processes. [ABSTRACT FROM AUTHOR]

Background: It is widely acknowledged that patient recruitment is a significant challenge and represents one of the primary reasons for drug development delays. Data from the Center for Information and Study on Clinical Research Participation (CISCRP) “Perceptions & Insights” study indicate that the 18- to 34-year-old Generation Y subgroup was the least willing to participate in a clinical trial. Methods: The willingness of Generation Y to participate in clinical studies was compared to that of older groups in the CISCRP study. These results were then compared to data from earlier studies. Results: Statistically significant differences existed between the willingness of Generation Y to participate in clinical studies when compared to older age groups. Generational perceptions and value differences were explored via corporate and sociological research findings to determine why disparities existed among age groups regarding the willingness for clinical trial participation. Conclusions: Preliminary results indicate that members of Generation Y are less willing to participate in clinical studies and that these differences are truly generational and not simply age related. [ABSTRACT FROM AUTHOR]

Background: Several regulatory guidelines recommend that assessments of endpoints supporting drug approval should be verifiable by applicants and the regulatory agencies to minimize the potential for bias. This becomes especially critical when assessments are not based on measurable data but are derived from the interpretation of measurements, when they require the application of complex endpoint assessments, or when a study cannot be blinded. To make such interpretation more robust, a verification of (subjective) assessments by an independent panel of experts is frequently utilized. The objective of this paper was to analyze how often adjudicated methods across efficacy and safety assessments were used in drug approvals in the European Union and United States in 2013 and early 2014. Methods: A total of 35 new molecular entities (NMEs) approved by the US Food and Drug Administration (FDA) and 88 European Medicines Agency (EMA) approvals in Europe were included in this analysis. Results: An adjudication method was used in phase III development programs in 69% of the NMEs approved in the United States and 41% of EMA approvals. Drugs developed for oncology and endocrinology typically used an independent review committee (IRC) in line with recommendations made in relevant regulatory guidance, whereas nervous systems, antivirals, and vaccines drugs typically did not. Central reading was most frequently used for efficacy endpoints or in a combination of efficacy endpoints and safety measures. Overall, approximately 20% to 30% of the primary endpoints analyzed in the US/EMA documentation were classified as subjective endpoints that were based on clinician-dependent (and subject-dependent) assessments. The remaining 70% to 80% were more robust endpoints that were reviewed by a central committee and/or were based on objective (measurable) endpoints, including laboratory tests. Conclusion: While no one size fits all, the need to include an IRC depends on the subjectivity of the primary endpoint, the therapeutic area concerned, the clinical trial design, the need to assess reliability of marginal positive events, or if a critical assessment is required for adverse event accuracy. [ABSTRACT FROM AUTHOR]

Background: As of 2014, the US FDA was considering policy options to promote accurate attribution of adverse events for biosimilars. In order to assess the identification and traceability of biologics from multiple sources, Tufts University’s Center for the Study of Drug Development conducted a study reviewing the current FDA Adverse Event Reporting System (FAERS) for reports related to insulin and growth hormone products. Methods: For this study, all primary suspect reports that were received by FAERS for human growth hormone (hGH) and human insulin between the fourth quarter of 2005 and the third quarter of 2013 were extracted and analyzed. Results: The rates of “accurate” brand (ie, identifiable) drug names were generally high, with a higher incidence for hGH drugs than for insulin drugs (92% of hGH primary suspect reports vs 84% of insulin primary suspect reports). Lot number completion rates were generally low, with a higher incidence for insulin drugs than for hGH drugs (37% of insulin primary suspect reports vs 13% of hGH primary suspect reports). There were 13.5% of insulin reports that could not be linked to manufacturers, while 7.5% of hGH reports could not be linked to a manufacturer. Conclusions: The completion and accuracy rates of FAERS data on biologics observed in this study are consistent with those observed in earlier studies and suggest that traceability in adverse event reports can be improved through more consistent use of brand names or other product specific identifiers and through more frequent inclusion of lot numbers. [ABSTRACT FROM AUTHOR]

There has been a proliferation of patient-centric initiatives supporting drug development planning and execution during the past 24 to 36 months. Patient centricity seeks to engage patients and the health care community as drug development partners and represents a fundamental departure from a legacy product-centric research and development paradigm. As the clinical research enterprise gains experience, it is critical that it executes patient-centric initiatives well, provides sufficient support, sets realistic expectations and requires reasonable return on investment (ROI). This article offers insights and suggestions for organizations looking to establish ROI expectation and evaluation of their patient-centric initiatives. The article is based on ideas and concepts that have been shared and discussed among stakeholders throughout the clinical research enterprise. [ABSTRACT FROM AUTHOR]

Historical studies of voluntary, spontaneous drug reports show poor attribution of adverse events to generic versions of commonly prescribed medications. As biosimilars enter the market place, it may be similarly difficult to accurately attribute adverse events to their respective reference products. At this time, lack of global consensus with regard to biosimilar naming conventions may result in drug reporting confusion, misattribution of adverse events and insufficient active monitoring of safety signals. Now, with the first biosimilar approval in the USA and many biosimilars expected to be launched globally in the near future, US Food and Drug Administration (FDA) guidance on biosimilar naming conventions will be essential. To inform the FDA and the global drug development community, the Tufts Center for the Study of Drug Development (Tufts CSDD) examined primary suspect reports sent to the FDA's Adverse Event Reporting System (FAERS) from US reporters for two biologics that have lost patent exclusivity--somatropin and human insulin--and extracted 4703 insulin reports and 6487 somatropin reports from FAERS. The results show that reporting practices are inconsistent between the two biologics that were evaluated and that manufacturer identifiability and traceability are lacking. Ways to improve biosimilar naming conventions and improve reporting practices are suggested. [ABSTRACT FROM AUTHOR]