By Bob Roehr
Significant portions of AIDS research will be shifted overseas under a huge reorganization of the trials networks proposed by the NIH National Institute of Allergy and Infectious Diseases (NIAID).
Many people believe this will negatively affect the capacity to treat patients in the U.S., as well as the ability to best manage the introduction of new classes of therapeutics that are on the horizon.
Funding for AIDS services, which is not keeping pace with the increasing number of people with AIDS/HIV who use those services or the escalating cost of drugs, and the CDC’s expanding effort to test more people to learn their HIV status, are factors combining to create a “perfect storm” scenario that threatens to inundate an already struggling system of AIDS care in the U.S.
The looming network reorganization is likely to be a hot topic for conversation among the world’s leading researchers when they gather in San Francisco for the 11th Conference on Retroviruses and Opportunistic Infections, February 8-11.
The proposed restructuring has been going on in plain sight. But the lethargic nature of bureaucratic change; the focus on principles behind those changes and the lack of specific numbers attached to them; and some general dissatisfaction with the clinical trials networks on the part of the few community activists who focus on research; have all blurred the impact that the proposed changes will have on American PWAs.
“The mission of NIAID/DAIDS is to help end the HIV/AIDS epidemic through basic and clinical research,” DAIDS division director Edmund Tramont told the AIDS Research Advisory Committee (ARAC) last September. He noted that 95% of that epidemic is occurring in developing countries and “an international research agenda will require both scientific and administrative adjustments.” At the same time, the DAIDS budget is leveling off, and priorities will have to be adjusted and refocused.
Tramont was very clear, the research networks that DAIDS supports to the tune of about $400 million a year are going to be restructured and recompeted. A huge amount of that effort will shift overseas beginning in fiscal year 2006.
Most of the Democratic candidates for president are attacking the Bush administration for policies that result in industry shipping jobs overseas. What are they going to say when money the federal government directly spends on research and the patient care associated with that research is shipped overseas?
“Even though our mission is to help end the epidemic, our way of doing that is through research. We don’t do care, or at least we don’t say we do,” DAIDS deputy director Jonathan Kagan told the January 26 meeting of the ARAC. Federal law precludes NIH from providing care; it can only do so within the context of research.
But patients volunteer to participate in clinical trials for a variety of reasons. For many PWAs, the most import reason is that it may be the only way for them to get access to care.
The conundrum of Kagan’s honestly in saying that NIH does not discuss the care that it provides through research has inhibited discussion of the impact that network reorganization will have on the provision of care to PWAs so much so that the issue has not even come up at any of the multiple public meetings that have discussed network reorganization over the last six months.
“We are trying to do everything, everywhere in the world, and yet, we were already stretched thin when we were trying to manage domestic HIV. Now the same people are basically trying to extend themselves to manage things internationally,” Henry Masur said at the September ARAC meeting. As director of the NIH Clinical Center he is an ex officio member of ARAC.
“It just seems to me that this is much too diffuse and we have to face the fact that we can’t do all of these things with the people and the resources that we have,” Masur said.
The Adult Clinical Trials Group (ACTG) is the largest of the treatment trials networks. Over time its focus has shifted from “is drug A better than drug B” to more intense studies trying to figure out how best to use the increasingly number of therapeutic options a complex matrix of what combinations and in what orders and also to identifying biological markers that give an early indication if a patient is vulnerable to a toxicity, lipodystrophy, or another problem that may be associated with a particular drug.
Robert “Chip” Schooley headed up the ACTG executive committee for many years and now is focusing on international research. With new classes of drugs like integrase inhibitors and entry inhibitors coming along, he believes “We’ll get a much faster answer learning how to use them if have the tools in place when they come along.” Now is not the time to scale back the ACTG.
He says, “The international program is an important component, but at the same time, it won’t be effective if we don’t have the domestic program upon which to build it.”
Two things are driving the international move. One is the commitment to implement treatment in the developing world and the other is the buildup to phase III trials for AIDS vaccines and microbicides.
A drug trial generally requires a few hundred patients to determine efficacy, while some complex trials comparing multiple drug regimens or treatment strategies need a few thousand patients.
In contrast, the Thai vaccine trial now underway is enrolling 16,000 participants. Most future vaccine and microbicide trials will be of a similar or larger scale.
DAIDS director Tramont fears that an early vaccine trial will show a low 10-20% level of protection. It won’t be enough to begin to vaccinate the population at large, but it may be sufficient to require that it replace the placebo used in current trials.
That means even bigger and longer trials for follow up vaccine candidates in order to detect modest improvements in protection. And the cost of those trials could go up exponentially. Vaccine trials hold the potential to eat up the entire AIDS research budget.
Nobody is questioning the need for these international programs; the issue is how to pay for them. Must that be at the expense of domestic programs?
A way out
The trials network restructuring is occurring through administrative channels where senior NIAID officials are doing the best job they can to identify and fund the highest research priorities within the context of the budget limitations they are given.
Two ways out of the crisis and its implications for AIDS research and care in the US are to add more money to the mix, or move the decision-making to another level where factors other than the scientific research agenda can be considered. Congress controls the purse strings and can design changes that protect patients and researchers from harm.
The entire NIH budget for AIDS research this year is about $2.8 billion dollars. NIAID gets slightly less than half of that but it has funded the vaccine research effort virtually by itself. Perhaps other institutes should contribute more toward that effort, though that might take money away from other research such as AIDS-related mental health issues or coinfections such as hepatitis C.
Another option would be to fund much of the expanded international HIV research agenda through other sources, rather than take it away from domestic research and the care that it supports. The President’s international AIDS initiative would be a logic place to look.
Concern also should be paid to preserving the research capacity and accompanying provision of care that has taken so long to establish at major research centers in the US.
In 2000 when the major vehicle for supporting AIDS services, the Ryan White CARE Act, was up for reauthorization, efforts to direct more resources to where the epidemic is moving, principally communities of color and the South, threatened to take funding away from cities that were first hit by the epidemic, particularly San Francisco.
The legislation solution was a “stop loss” provision assuring that no jurisdiction would see a decrease in funding, while new money was disproportionately channeled to underserved areas to help them catch up.
The NIH AIDS research agenda is on a path that will shift much of that activity to locations overseas, at the expense of those at home. It will continue on that path until people demand other solutions.