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.
May
Susanne
S
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
Letendre
Scott
S
Haubrich
Richard
R
McCutchan
J Allen
JA
Heaton
Robert
R
Capparelli
Edmund
E
Ellis
Ronald
R
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