Stella Stergiopoulos

Evaluating the completeness and accuracy of MedWatch data.

The Food and Drug Administration’s MedWatch system—a voluntary surveillance program—received 600,000 adverse event reports on marketed drugs and devices in 2011. The Food and Drug Administration credits the MedWatch system with improving awareness, and expediting early detection, of drug and device risks and in illuminating the adoption of medical treatments. Reporting bias has been acknowledged as a limitation of the MedWatch system. No systematic assessment of the accuracy and completeness of adverse event reporting has been conducted, yet inaccurate adverse event reporting may lead drug safety professionals to draw incorrect conclusions, manufacturers may be wrongly forced to suspend and withdraw medications and interventions, health professionals may mistakenly alter their clinical practices, and patients may be denied safe and effective treatments. In 2011, the Tufts Center for the Study of Drug Development gathered and analyzed 10.2 million adverse event reports filed with the MedWatch system. Patient information was generally complete and accurate. Suspect product information, on the other hand, showed high levels of incomplete and inaccurate data. Start and end dates of suspect product use had 37% and 23% completion rates, respectively. Dosage level was completed only 31% of the time, and product lot numbers had only a 9% completion rate. More than 25% of the names of reported suspect products were inaccurate, and 31% of suspect product start dates were inaccurate. Higher levels of completion and accuracy were associated with reports filed closer to the date when the adverse event was observed. Implications of the results and suggested improvements are discussed.

Quantifying the magnitude and cost of collecting extraneous protocol data.

Although most research professionals believe that protocol designs contain a growing number of unnecessary and redundant procedures generating unused data, incurring high cost, and jeopardizing study success, there are no published studies systematically examining this issue. Between November 2011 and May 2012, Tufts Center for the Study of Drug Development conducted a study among a working group of 15 pharmaceutical companies in which a total of 25,103 individual protocol procedures were evaluated and classified using clinical study reports and analysis plans. The results show that the typical later-stage protocol had an average of 7 objectives and 13 end points of which 53.8% are supplementary. One (24.7%) of every 4 procedures performed per phase-III protocol and 17.7% of all phase-II procedures per protocol were classified as “Noncore” in that they supported supplemental secondary, tertiary, and exploratory end points. For phase-III protocols, 23.6% of all procedures supported regulatory compliance requirements and 15.9% supported those for phase-II protocols. The study also found that on average,

New Governance Mechanisms to Optimize Protocol Design

1.7 million (18.5% of the total) is spent in direct costs to administer Noncore procedures per phase-III protocol and

A Tool for Predicting Regulatory Approval After Phase II Testing of New Oncology Compounds.

0.3 million (13.1% of the total) in direct costs are spent on Noncore procedures for each phase-II protocol. Based on the results of this study, the total direct cost to perform Noncore procedures for all active annual phase-II and phase-III protocols is conservatively estimated at

The Impact of Protocol Amendments on Clinical Trial Performance and Cost

3.7 billion annually, not including the indirect costs associated with collecting and managing Noncore procedure data and the ethical costs of exposing study volunteers to unnecessary risks associated with conducting extraneous procedures.

Identifying and Quantifying the Accuracy of Product Name Attribution of US-Sourced Adverse Event Reports in MedWatch of Somatropins and Insulins

Pharmaceutical and biotechnology companies are actively seeking ways to optimize protocol design. An emerging approach has been the creation of a new governance mechanism designed to evaluate protocol feasibility and simplify design before final protocol approval. In late 2012, the Tufts Center for the Study of Drug Development conducted a qualitative in-depth assessment of 10 major pharmaceutical companies that have implemented these new governance mechanisms since 2009. Detailed profiles of each company’s feasibility review mechanism are discussed including committee missions and objectives, positioning, composition, staffing models, reporting flow, implementation challenges, and measured impacts to date.

Regulatory Definitions and Good Pharmacovigilance Practices in Social Media Challenges and Recommendations

We developed an algorithm (ANDI) for predicting regulatory marketing approval for new cancer drugs after phase II testing has been conducted, with the objective of providing a tool to improve drug portfolio decision‐making. We examined 98 oncology drugs from the top 50 pharmaceutical companies (2006 sales) that first entered clinical development from 1999 to 2007, had been taken to at least phase II development, and had a known final outcome (research abandonment or regulatory marketing approval). Data on safety, efficacy, operational, market, and company characteristics were obtained from public sources. Logistic regression and machine‐learning methods were used to provide an unbiased approach to assess overall predictability and to identify the most important individual predictors. We found that a simple four‐factor model (activity, number of patients in the pivotal phase II trial, phase II duration, and a prevalence‐related measure) had high sensitivity and specificity for predicting regulatory marketing approval.

Mobile Nurse Services in Clinical Trials Usage and Industry Perceptions

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

Cost Drivers of a Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia Phase 3 Clinical Trial

141,000 for a phase II protocol and

Baseline Assessment of a Global Clinical Investigator Landscape Poised for Structural Change

535,000 for a phase III protocol. Conclusions: The study findings provide insights into optimizing development planning, protocol design, and clinical trial management practices.