DDC: EXPANDED ACCESS ANNOUNCED FOR PATIENTS WITHOUT OTHER OPTIONS

On June 25 Hoffmann-LaRoche will begin an expanded access
program to provide ddC (proprietary name HIVID) to patients who
have failed or been intolerant to AZT and are intolerant to ddI.
This program will proceed in parallel with the formal clinical
trials of the drug (for more information about the trials, see
the last issue of AIDS TREATMENT NEWS, May 18, 1990). Those
eligible for the new program could not participate in the trials,
since they must be unable to use AZT in order to qualify for the
expanded access; those in the formal trials of ddI must be able
to use AZT, since they might be randomly assigned to it.

Because ddC has never been tested on this patient
population, the new program will begin gradually. At first only
50 people will be accepted and only from physicians who have
prior experience with ddC. After 25 of them have been monitored
for at least four weeks without serious problems, the program
will be expanded to 200 people, and any physician with AIDS
experience will be allowed to enter patients. After 100 people
have been followed for 16 weeks without unexpected problems,
there will be no numerical limit to how many may enter the
program, if they meet the medical qualifications.

All patients will be randomized to one of two doses; the
highest dose will be the same as that used in the formal trials.
Random assignment of doses greatly increases the useful
information a trial can provide, because it allows scientists to
look for a dose- response relationship in both toxicity and
efficacy. (In this program the main reason for varying the dose
is to collect safety information for these patients.)

To be eligible for this program, patients must:

* Either be unable to tolerate AZT (under the criteria used
in the ddI expanded-access program), or meet other criteria
indicating that AZT was ineffective for them;

* Also be unable to tolerate ddI, for reasons other than
peripheral neuropathy (which is a toxicity of ddC as well as of
ddI);

* And also not have cancer (KS is OK, however, and so is
basal cell carcinoma).

Starting June 25, physicians can call 800/ddC-21-HIV,
Monday through Friday 9 a.m. to 8 p.m. Eastern time, for more
information about this program.



PARALLEL TRACK PROPOSAL RELEASED: PUBLIC COMMENT ACCEPTED THROUGH JULY 20

The long-awaited proposal for a formal "parallel track" for
early access to certain experimental drugs in phase II clinical
trials, for people not eligible for those trials, has been
published in the Federal Register (May 21, pages 20656-20659).
The public- comment period ends July 20, and it is important to
write to the address below to support this program.

How is the official "parallel track" different from the
expanded- access program for ddI (and now for ddC also see
article in this issue of AIDS TREATMENT NEWS)? The ddI program
is like the parallel track, but it was started separately to
avoid being delayed until the formal program could begin.

The AIDS Research Advisory Committee (ARAC)

The parallel track proposal provides an official structure
for deciding which drugs to recommend for early-access release.
A major part of this structure, the AIDS Research Advisory
Committee (ARAC), is "composed of outside scientists and
physicians experienced with AIDS, persons with HIV-related
diseases, and others." It will be administered by the U. S.
National Institute for Allergy and Infectious Diseases (NIAID).

The ARAC is only advisory; the FDA makes the final decision
of whether a drug will be released. And of course the
pharmaceutical-company sponsor must be willing and able to make
the drug available.

The parallel-track proposal allows sponsors to bypass the
ARAC if they want, and submit their proposals directly to the FDA
instead. (We consider this option a good idea, simply because
nobody knows for sure how the ARAC will work in practice.
Pharmaceutical companies will usually choose to go through the
ARAC, because if they have a good program, that body will be an
ally and if they don't, they will be stopped at the FDA in any
case. But if by mischance the ARAC becomes bogged down or
otherwise fails to work properly, another option would be
available.)

We consider the ARAC especially important because it creates
a public body with official status to determine which drugs in
clinical trials should become more available.

Other Parts of the Parallel-Track Proposal

Besides ARAC, the parallel-track proposal also calls for:

* Creation of a national IRB (Institutional Review Board)
for the parallel-track protocols. While local IRBs could still
review any protocol, the national IRB could avoid delays and
other problems which would result from relying only on the local
groups. Until the national IRB is established, the ARAC will
appoint a subcommittee to do its job temporarily.

* Emphasis on education of physicians and potential
participants in parallel-track programs, to make sure that
physicians are informed on how to use the drugs, and that the
risks and benefits of participating are understood.

* Use of existing IND regulations to allow pharmaceutical
companies to recover costs in some cases by charging for
participation, but only " in the unusual circumstance in which
the trial could not continue" (without charging fees), and only
with the permission of the FDA.

* Criteria for terminating parallel-track access to a
particular drug, for example if there is unreasonable risk to
participants, if a better product becomes available, or if the
parallel-track access interferes with clinical trials of any
drug.

The parallel-track proposal as now published will apply only
to HIV-related drugs at this time. It is, however, described as
a pilot effort; if successful it could be expanded to include
treatments for other diseases also.

Address for Comments

Comments about the parallel-track proposal can be sent to:
Parallel Track Policy, National AIDS Program Office, 200
Independence Avenue SW, Room 738-G, Washington, DC 20201. For
more information, write to Dr. Valerie Satlow at the above
address, or call Dr. Satlow or Donald Pohl at 202/472-4248.

We believe that the existing parallel-track proposal is the
best we can get at this time and should be accepted as is;
changes can be made later, if needed. We are concerned that
opponents of expanded access may try to weaken the parallel track
to make it less useful, as they did with the "treatment IND"
regulations which became effective three years ago but have had
limited use since.