ACTG Rescue Plan: Tome of Recommendations Would Abolish ACDDC, Mandate Costing-Out and Establish Advisory Review Group

"The up-coming ACTG re-competition provides an opportunity to re-envision AIDS clinical research for the next 5 years. It looks likely, however, that this opportunity will be missed. Current plans call for only incremental changes. They address the ACTG in isolation, rather than in the context of NIH's overall $300M AIDS clinical research budget. Moreover, they have been developed without a comprehensive discussion of the changing scientific and public health imperatives of the AIDS epidemic."

The detailed recommendations contained in Mark's report, "ACTG Rescue Plan," each represent aspects of an over-arching problem with current clinical research on AIDS: the research mechanism determines the research methodology. "Thus, good science," Mark writes, "is held hostage to financial, technical and personal limitations of the various networks (ACTG, CPCRA, etc.). The ACTG attempts to cover the field, yet is unable to do so with current resources; it fails to cooperate efficiently with CPCRA, let alone with other NIH networks; and there are no plans to improve the situation through the recompetition."

"The NIAID FY1996 budget justification states that: 'This recompetition of the Adult component of the ACTG will mark an important departure from the past. Research priorities will continue to diverge from classical drug development toward clinical studies which are uniquely in the purview of government (i.e., driven primarily by public health priorities and/or unlikely to proceed under support of the private sector), and which will enhance knowledge of the pathogenesis of HIV disease through comprehensive evaluation of therapeutic interventions. This will include much greater attention to research and development of: novel strategies to combat the primary disease based on knowledge of pathogenesis, molecular biology, and factors influencing therapeutic efficacy; immune therapies; simultaneous prophylaxis against multiple opportunistic infections; surrogate endpoints for monitoring therapy and developing new approaches to therapy; improved methods for rapid diagnosis characterization of opportunistic agents; and better therapeutic strategies to treat malignant, neurological, and women-specific complications of HIV infection.'

'To achieve this, the NIAID requires an extremely flexible multicenter clinical trials mechanism with a comprehensive scientific agenda and a broad range of capabilities. These include: capacity to conduct clinical trials across the spectrum from small, laboratory-intensive, innovative pilot/phase I studies to large randomized phase III studies; access to large number of patients in order to ensure ability to complete large studies involving patients with OIs or unusual conditions; and laboratory resources to address the numerous, high priority ancillary/nested studies needed to develop the surrogate marker and assay research agenda.'

"Clearly NIAID anticipates that the ACTG will be able to conduct virtually any kind of clinical trial. This is not possible now, and will be impossible in the future as well. The ACTG cannot be all things to all researchers, and it cannot achieve all of these goals properly with its $68M budget. To achieve the goals itemized by NIAID for the ACTG, the entire NIH clinical research budget for AIDS would be necessary."

"OAR and NIAID need to figure out how to optimize the use of NIH's current $300M and how to situate the ACTG where it belongs in the larger context. DAIDS needs to focus on how to encourage the ACTG to do what it does best, and develop new mechanisms, or shift resources to existing mechanisms (e.g., CPCRA) to answer questions which the ACTG is not optimally suited to answer. The ACTG group leadership needs to identify, in its application, how it will prioritize between and within research areas, both scientifically and financially. The new ACTG leadership must develop a credible plan to say 'no' to second-rate scientific protocols, or to second-tier scientific questions which, while fundable in a world of unlimited resources, are not fundable given resources limitations. Heretofore, neither the Executive Committee nor DAIDS has been willing or able to say 'no.'"

"To address all the issues itemized previously, NIAID (or OAR) should charter a new operational advisory committee, the Therapeutics Working Group to oversee NIAID clinical research programs on an on-going basis, to review the appropriateness of the NIAID, ACTG and CPCRA research agenda(s), and to review proposed protocols for scientific, resource and mechanism adequacy."