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Meeting Practical Challenges of a Trial Involving a Multitude of Treatment Regimens: An Example of a Multi-Center Randomized Controlled Clinical Trial in NeuroAIDS

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Abstract

Many clinical trials compare one specific treatment to a control or standard treatment. In HIV therapeutics, such fixed-regimen designs may be problematic as individualized treatment regimens are standard practice. Designing and implementing a trial that allows individualized treatment options poses particular challenges. In this example of a clinical trial in NeuroAIDS, it is hypothesized that some antiretroviral drugs [i.e., those that penetrate the blood–brain barrier sufficiently to inhibit HIV in the central nervous system (CNS)] will improve HIV neurocognitive impairment, whereas non-penetrating antiretrovirals will not be as effective in improving neurocognitive function. To test this hypothesis, a uniquely designed strategy trial was developed that consists of three essential components: (1) a scoring system that ranks regimens for CNS penetration based on semiquantitative criteria, (2) committee-established individualized regimen options that allow randomization to opposite ends of the CNS penetration spectrum, and (3) timely implementation across multiple centers via web-based resources. For the proposed trial, the three components are combined with an adaptive randomization scheme to minimize potential confounding by several important factors. A small pilot study demonstrated the feasibility and acceptability to providers. In conclusion, an innovative design can provide solutions to challenging practical issues in trials with multiple treatment options.

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Acknowledgments

This work was supported in part by the National Institutes of Health (R01 MH58076, R. Ellis; P30 MH62512, I. Grant; K24 AI64086 and AI36214, R. Haubrich), the UCSD Center for AIDS Research (CFAR), and the San Diego ACTG CTU (AI27670, C. Benson) and the University of California University-wide AIDS Research Program (UARP; CH05-SD-607)

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Authors and Affiliations

  1. Division of Biostatistics and Bioinformatics, Department of Family & Preventive Medicine, and Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive-M/C 0717, La Jolla, CA, 92093-0717, USA

    Susanne May

  2. Department of Medicine, University of California, San Diego, 150 West Washington St., San Diego, CA, 92103, USA

    Scott Letendre, Richard Haubrich & J. Allen McCutchan

  3. Department of Psychiatry, University of California, San Diego, 150 West Washington St., San Diego, CA, 92103, USA

    Robert Heaton

  4. Department of Pediatrics, University of California, San Diego, 200 W. Arbor Drive #8214, San Diego, CA, 92103, USA

    Edmund Capparelli

  5. Department of Neurosciences, University of California, San Diego, 150 West Washington St., San Diego, CA, 92103, USA

    Ronald Ellis

Authors
  1. Susanne May
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  2. Scott Letendre
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  3. Richard Haubrich
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  4. J. Allen McCutchan
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  5. Robert Heaton
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  6. Edmund Capparelli
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  7. Ronald Ellis
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Corresponding author

Correspondence to Ronald Ellis.

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May, S., Letendre, S., Haubrich, R. et al. Meeting Practical Challenges of a Trial Involving a Multitude of Treatment Regimens: An Example of a Multi-Center Randomized Controlled Clinical Trial in NeuroAIDS. Jrnl Neuroimmune Pharm 2, 97–104 (2007). https://doi.org/10.1007/s11481-006-9057-8

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  • DOI: https://doi.org/10.1007/s11481-006-9057-8

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