Government AIDS Research: the ACTG. Interview with Michael S. Saag, M.D.

Michael S. Saag, M.D., a researcher at the University of Alabama at Birmingham, is a new member of the Executive Committee of the AIDS Clinical Trials Group (ACTG), the main U.S.-government program for clinical trials of AIDS drugs. Among other responsibilities, Dr. Saag directs the subcommittee in charge of the ACTG's interaction with outside groups, including the pharmaceutical industry, community organizations, and government medical-research teams outside the ACTG.

ATN: What is most important for our readers about the ACTG?

Saag: I think the ACTG is a very valuable resource for the country. It has taken a lot of criticism, some of it fairly applied. But the success of the ACTG is not widely understood.

If you think about what happens in clinical practice today in a doctor's office, and compare it to six or seven years ago, you will find that much -- perhaps 70 to 80 percent of the activities of a physician, in terms of new approaches to management of their HIV patients -- was initiated through the results of an ACTG trial. When you go to conferences, and hear discussions about patient care and trial results, you almost always hear references to ACTG studies. There have been many contributions, not only in the primary infection area [treating HIV itself], but especially in opportunistic infectious diseases. What types of prophylaxis work best, what is the best treatment for cryptococcal meningitis or pneumocystis pneumonia or CMV retinitis, these results have usually come from ACTG trials. People should recognize that the ACTG has made major contributions.

Also, much that goes on behind the scenes at the ACTG helps pharmaceutical-industry studies. Consider the quality assurance program that assures that virology labs working with the ACTG all operate in a standardized way, and that the measurements of T-cell counts are standardized. All these spill over into industry trials. The sites that are ACTG funded also can do industry studies, and whenever a company goes to those sites, it is using the same laboratories that are ACTG certified. That's been a very important plus for studies that are not ACTG affiliated.

In the future, due to a recent reorganization, the work of the ACTG will be based more directly on a foundation of its scientific agenda. In the past, an individual researcher at an ACTG site would come up with an idea, propose it as a concept sheet, and go through the system from the bottom up. While that is democratic and taps into the great resources of a number of very talented people, it can also be inefficient. In the future, all these researchers with their talents and ideas will first come together to brainstorm and come up with a scientific agenda, and then develop specific protocols to address that agenda. This should speed protocol development and the conduct of trials.

ATN: We have heard of many cases where concept sheets don't go anywhere, probably because the leadership does not agree with them. This change might help to avoid that problem.

Saag: I think it will. And I think the other problem is that some members of the ACTG, especially in leadership positions, get so inundated with paper, having to keep up, that it's hard to give every concept sheet a clean, fresh look every time. You never know when one is going to be coming in.

So we will back up and say, "What are the big-picture issues that we should be addressing as a group?" We will define those questions, establish that agenda, prioritize, and then ask, "What kind of trials will help us answer this question?" I believe that the proposal I have seen will reduce protocol development time -- going from an idea to a protocol open for enrollment -- from over 230 days down to about 85 days. This is about to be implemented.

Also, we also should keep in mind what would happen if the ACTG did not exist. Suppose it had never been created; what would people be saying about what ought to be done? They would say that we should get together some of the best scientists and clinical investigators in the country, and form a network where they could work together and study new approaches to treat the disease. Also, you would want to bring those people together, at least semi-annually, to talk about progress, discuss current issues, decide directions together, and then implement those new protocols and studies that they come up with. That is precisely what the ACTG is. The problem is that it has been inefficient in its ability to get things done quickly; it has been too bureaucratic in the past. I think that with the reorganization it will become more streamlined, and enable us to fulfill those desperately needed missions of having some of the better investigators in the country working together on joint projects.

I'm very encouraged by what is happening. There is a dynamic interaction within the ACTG leadership, and a lot of dedication to making the organization run efficiently, and be as productive as possible. I'm optimistic that we can do that. But it will take much work to get us to that next level.

ATN: Recently some leading scientists have called for a redirection of AIDS research. [See "AIDS Research Direction: New Scientific Approach?," AIDS Treatment News #199, May 20, 1994.] Some have interpreted Dr. Fields' recent paper as calling from a shift from clinical to basic research; but what he really seems to be saying is that there should be better communication between the laboratory studies and the clinical trials which test new drugs in patients. Where do you think we should focus now?

Saag: There has been a fairly strong emphasis on basic science from NIAID [the U.S. National Institute of Allergy and Infectious Diseases, which runs the ACTG] over the last five or six years. In 1987, there was a project called Programs for Excellence in Basic Research on AIDS (PEBRA); our team at the University of Alabama was one of the recipients of that award, and that is what started us coordinating the clinical side and the basic science side. That's the kind of initiative we should continue with.

NIAID has continued this approach, with the new SPIRATS grants, which encourage investigators to work together from the beginning of a new concept of treatment, to developing that approach in the laboratory, and carrying it through all the way to the initial clinical trials. [Note: SPIRATS stands for Special Program for Innovative Research on AIDS Treatments. The first five to eight SPIRATS grants are expected to be awarded in August 1994.] This is an important initiative that encourages creativity among investigators within different disciplines, having them work together.

This kind of approach is where progress in HIV will come from. I think we do it at the University of Alabama about as well as it's done anywhere; it was the U.S. National Institutes of Health programs that got us going. The PEBRA, our Center for AIDS Research, and other government programs, have all been used to have scientists from different disciplines work together. This is the critical issue that should be emphasized, rather than segregating out more money for basic science, or for clinical science. We are trying to get money used in a way that maximizes the interaction between the different disciplines and different research groups.