Meeting practical challenges of a trial involving a multitude of treatment regimens: an example of a multi-center randomized controlled clinical trial in neuroAIDS.
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.
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. smay@ucsd.edu
Susanne
S
May
Scott
S
Letendre
Richard
R
Haubrich
J Allen
JA
McCutchan
Robert
R
Heaton
Edmund
E
Capparelli
Ronald
R
Ellis
D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000523:psychology* / Q000821:virology; D000163:Acquired Immunodeficiency Syndrome / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000523:psychology* / Q000821:virology; D000818:Animals; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D005240:Feasibility Studies; D006801:Humans; D015337:Multicenter Studies as Topic / Q000379:methods*; D010865:Pilot Projects; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D016896:Treatment Outcome