Strategy management in collaborative clinical research partnerships.

PURPOSE: Today's clinical trial partnerships frequently join multi-disciplinary investigators and stakeholders, from different countries and cultures, to conduct research with a broad array of goals. This diversity, while a strength, can also foster divergent views about priorities and what constitutes success, thereby posing challenges for management, operations, and evaluation. As a sponsor and partner in such collaborations, we seek to assist and support their development and implementation of sound research strategies, to optimize their efficiency, sustainability, and public health impact. This report describes our efforts using an adaptation of the well-established Kaplan-Norton strategy management paradigm, in our clinical trials setting. We share findings from our first test of the utility and acceptance of this approach for evaluating and managing research strategies in a collaborative clinical research partnership. RESULTS: Findings from pilot studies and our first implementation in an ongoing clinical research partnership in Liberia, provide initial support for our hypothesis that an adapted version of the Kaplan-Norton strategy management model can have use in this setting. With leadership from within the partnership, analysis artifacts were gathered, and assessments made using standardized tools. Practical feasibility, resonance of the findings with partners, and convergence with other empirical assessments lend initial support for the view that this approach holds promise for obtaining meaningful, useable results for assessing and improving clinical research management. CONCLUSIONS AND IMPLICATIONS: Engaged leadership, thoughtful timing to align with partnership planning cycles, support for the process, and an eye towards the collaboration's long-term goals appear important for developing model understanding and practice. Skepticism about evaluations, and unease at exposing weaknesses, may hinder the effort. Acceptance of findings and associated opportunities for improvement by group leadership, support a growing sense of validity. Next steps aim to test the approach in other partnerships, streamline the methodology for greater ease of use, and seek possible correlations of strategy management assessments with performance evaluation. There is hardly a better example than the COVID-19 pandemic, to spotlight the need for efficient and effective clinical research partnerships to address global health challenges. While heartened by the collaborative spirit driving the effort so far, we cannot let our enthusiasm lull us into thinking that nobility of purpose or an abundance of good will is sufficient. Careful monitoring and adjustment of clinical research strategy in response to changes (e.g., demographics, pathogen evolution, research acceptance, political and cultural environments) are vital to making the needed adjustments that can guide these programs toward successful outcomes. We hope that our work can raise awareness about the importance, relevance, and feasibility of sound strategy management in clinical research partnerships, especially during this time when there is so much at stake.

Developing training for Data Safety Monitoring Board members: A National Institute of Allergy and Infectious Diseases case study.

BACKGROUND: Data Safety Monitoring Boards primarily review accumulating data on clinical trials and provide recommendations to sponsors on whether a protocol should continue as planned, be modified, or be terminated. Data Safety Monitoring Boards often provide their recommendations based upon accumulating data to which only their members are given access. Despite the substantial responsibilities assumed by Data Safety Monitoring Board members, there is limited information in the literature about the unique knowledge they must possess and, consequently, the training content needs that are required in order for them to fulfill their obligations. PURPOSE: This article describes how the National Institute of Allergy and Infectious Diseases identified the knowledge that Data Safety Monitoring Board members should acquire and the computer-based training they developed to address the learning needs of the National Institute of Allergy and Infectious Diseases assembled Data Safety Monitoring Board members. METHODS: The National Institute of Allergy and Infectious Diseases conducted a comprehensive literature search and interviewed Data Safety Monitoring Board subject matter experts, including Data Safety Monitoring Board members and chairs from academic institutions, pharmaceutical companies, and the National Institutes of Health to (1) assess whether Data Safety Monitoring Board training is an identified need, (2) evaluate whether Data Safety Monitoring Board training has been developed, and (3) formulate suitable learning objectives. Data Safety Monitoring Board training modules were developed based on the identified learning objectives identified from the interviews. RESULTS: Three Data Safety Monitoring Board training modules were developed and formatted for web-based access, which is free of charge to the public at https://dsmblearningcenter.niaid.nih.gov. The modules include the following: an introduction to the objectives and purpose of Data Safety Monitoring Boards, the organization and responsibilities of Data Safety Monitoring Boards, and a review of statistical topics. LIMITATIONS: The complex concepts that Data Safety Monitoring Board members must apply to their deliberations and decisions require practice and application that come through hands-on experience. To build competency in the Data Safety Monitoring Board member role, not only does a member need to understand these complex concepts but also the member must have the opportunity to practice and apply this knowledge to real-life situations. Additional resources to facilitate practice and application of the complex issues that Data Safety Monitoring Boards deal with should be considered. The computer-based training is targeted to new and inexperienced Data Safety Monitoring Board members. Ongoing learning opportunities should be developed for experienced Data Safety Monitoring Board members. Non-English training must also be considered. CONCLUSION: The National Institute of Allergy and Infectious Diseases identified that training is not widely available for Data Safety Monitoring Board members to build the unique knowledge and skills necessary to serve on Data Safety Monitoring Boards. Consequently, National Institute of Allergy and Infectious Diseases developed publicly available web-based Data Safety Monitoring Board training modules for new or inexperienced members. Additional tools and resources are needed to help Data Safety Monitoring Board members acquire the knowledge and skills to serve their critical function in clinical research and to maximize research participant protections.

Single-dose and steady-state pharmacokinetics of tenofovir disoproxil fumarate in human immunodeficiency virus-infected children.

Tenofovir disoproxil fumarate (DF) is a potent nucleotide analog reverse transcriptase inhibitor approved for the treatment of human immunodeficiency virus (HIV)-infected adults. The single-dose and steady-state pharmacokinetics of tenofovir were evaluated following administration of tenofovir DF in treatment-experienced HIV-infected children requiring a change in antiretroviral therapy. Using increments of tenofovir DF 75-mg tablets, the target dose was 175 mg/m(2); the median administered dose was 208 mg/m(2). Single-dose pharmacokinetics were evaluated in 18 subjects, and the geometric mean area under the concentration-time curve from 0 h to infinity (AUC(0- infinity )) was 2,150 ng. h/ml and the geometric mean maximum concentration (C(max)) was 266 ng/ml. Subsequently, other antiretrovirals were added to each patient's regimen based upon treatment history and baseline viral resistance results. Steady-state pharmacokinetics were evaluated in 16 subjects at week 4. The steady-state, geometric mean AUC for the 24-h dosing interval was 2,920 ng. h/ml and was significantly higher than the AUC(0- infinity ) after the first dose (P = 0.0004). The geometric mean C(max) at steady state was 302 ng/ml. Tenofovir DF was generally very well tolerated. Steady-state tenofovir exposures in children receiving tenofovir DF-containing combination antiretroviral therapy approached values seen in HIV-infected adults (AUC, approximately 3,000 ng. h/ml; C(max), approximately 300 ng/ml) treated with tenofovir DF at 300 mg.