Back in 1981, when this plague that has now ravaged the planet and forever changed the way its people see sex made its grisly debut, no one would have dared fathom that some 20 years later we'd still be trying to figure out how the dastardly virus wreaks its immunological havoc - or searching blindly for therapeutics to stop it in its tracks. And yet that day is rapidly approaching. This paralyzing reality was made none too clear by the casual mention of the year "2001" (the fifth and final year of the up-coming five-year ACTG grant renewal period) amidst the commotion at the NIAID's recent pre-application meeting, held in one of the many aesthetically offensive pre-fab hotels along Wisconsin Avenue in picturesque Bethesda, MD.
The get-together, which was attended by some 100 current and would-be federal investigators, was billed as an informational pre-application meeting but turned out to be more a bizarre hybrid of the children's games "Marco Polo" and "Telephone." While DAIDS staffers Jack Killen, Bill Duncan, Peter Jackson and the like stood before the frazzled throngs attempting to lay out the proposed new ACTG structure and application procedures for the next 5-year cycle (1996-2001), a cursory gaze around the room caught sotto voce editorializing, exasperated palms slapped flatly across foreheads and faces twisted in all possible contortions of confusion. Every now and then DAIDS provacateuse Patricia Reichelderfer, a veritable Jack-in-the-box (though always smartly festooned) would pop up from her seat way in back to correct an occasional misstatement by those at the mike.
The lion's share of the confusion could be traced to the concept of competing "Central Groups" (and to something called "ATLs," Advanced Technology Labs). Born of the buzz that some of the younger ACTG investigators were plotting a mutiny, DAIDS architects decided to open this next RFA up to the possibility of multiple AIDS clinical trials groups, each with its only operations, stats and laboratory support. The rather loosely worded description in the RFA itself merely explained that "each application for an adult ACTG Central Group must demonstrate the ability to recruit and support a minimum capacity of 1,250 new patients per year." But at the pre-application meeting it became clear that DAIDS was expecting no more than two separate groups to apply, three tops. As of September 29, however, there had been only one Letter of Intent received; apparently the quiet revolution down in Birmingham had fizzled out.
"Approximately $60M will be available in fiscal year 1996 (that's an $8M annual cut vis--vis last year) for the first year of support for awards made under this RFA," the document announced. Of this total, $3.5 is to be reserved "exclusively to support clinical trials units (ACTUs) at minority institutions." Minority institutions, defined as "those that have more than 50 percent minority students enrollment and award an MD, DDS, DVM or other doctorate degrees in the health professions."
Budget requests for clinical units are not to exceed $1.7M in total costs per year for all activities at the unit - including recruitment and retention of new patients, protocol mandated virology and immunophenotyping, and costs associated with the follow-up of patients continuing on ACTG protocols at "incumbent applicant institutions."
Historically, the protocol-specific mean costs per patient per year for ACTG Phase I, Phase II and Phase III studies have run approximately $6,300, $7,500 and $4,300, respectively. These costs, however, do not include resources devoted to patient recruitment, screening, data management, quality assurance, program administration or supplies. In addition to the $1.7M per site, the Group Leader may also request a discretionary budget to fund innovative pilot studies as well as to supplement the budgets of collaborating institutions.
Applications are to be reviewed by the Division of Research Grants (DRG) for "completeness" and by the NIAID staff to determine "responsiveness to the RFA." Applications that make this preliminary cut will then be evaluated for "scientific and technical merit" by a peer review group convened by NIAID.
The review will be conducted in two stages. A review panel will review the ACTG Central Group application(s), focusing on the "merit of the proposed scientific agenda" and "factors that will affect the group's ability to achieve its stated goals and objectives." The review panel will also review the application from the Statistical and Data Management Center (SDAC) associated with each ACTG Central Group application. The review of the ACTU applications will focus on each unit's ability "to contribute to the ACTG Central Group's scientific agenda, as well as the ability and expertise to conduct AIDS clinical trials, including accruing 75 or more demographically representative patients per year." Applications judged to be competitive will be discussed and be assigned a priority score. A second level of review will be provided by the National Advisory Allergy and Infectious Disease Council where, it appears, the final selections are to be made more or less by Division of AIDS (DAIDS) staffers - with the peer review appraisals as their guide.
DAIDS' Mary Kirker explained that the Division expects to fund some 22-29 individual ACTUs. Some 36 were funded in the last grant period, but it's difficult to compare because of the recent separation into Adult and Pediatric sites. As the day wore on, much of fog seemed to lift, aided greatly by Ms. Kirker's refreshing candor: "This is a very confusing, uh, complicated RFA."