
AIDS TREATMENT NEWS Issue #245, April 19, 1996
   phone 800/TREAT-1-2, or 415/255-0588

CONTENTS:

Crixivan(R) Price Break for Cash Customers: $97 Per Month 
Less, If You Ask

Protease Inhibitors: Ritonavir and Saquinavir Combination 
Trial Recruiting

Protease Inhibitors: Background Information

Delavirdine Available on Expanded Access

Sinusitis: Helpful Background, Treatment Article

Chinese Medicine: Qigong Exercise Tape Available

rGP-160 Treatment Vaccine (VaxSyn): Canadian Study Finds No 
Benefit

FDA Reform in Congress: Interview with Peter Barton Hutt

FDA Reform in Congress: FDA's Concerns

Vancouver Conference: Make Travel Plans Now. Focus, Program, 
& Satellite Meetings


***** Crixivan(R) Price Break for Cash Customers: $97 Per 
Month Less, If You Ask

After extensive protest against the large markup on Merck's 
protease inhibitor (from $12 per day which is Merck's price, 
to the $16.50 per day retail price for cash customers), 
Stadtlanders Pharmacy has found a way to reduce the cash 
price from $16.50 to $13.27 (consistent with it contractual 
obligations to insurance companies and managed-care plans, 
which already get discounted prices). They will do this by 
honoring a discount card which has long been provided by 
another mail-order pharmacy, Community Prescription Service 
(CPS). The CPS card costs $18, and is honored by about 60% of 
pharmacies in the U.S., who give a negotiated below-retail 
price to card holders, not only for Crixivan.

Note: Due to a special temporary distribution program for 
indinavir (Crixivan), described in AIDS TREATMENT NEWS #244, 
April 5, 1996, most patients can only order this drug through 
Stadtlanders.

It appears to be most convenient if you get the card in 
advance directly through CPS. For more information, or to 
order the discount card, call CPS at 800/842-0502. But you 
can also ask for the card when you call Stadtlanders for your 
monthly Crixivan prescription; they can order it for you from 
CPS and give you the discount immediately.

This program was announced on April 18, and largely 
negotiated the day before. It may take a few days or more for 
Stadtlanders' phone operators to be told about the program 
and trained in how to use it.

Note: The reason for this price irrationality is that there 
has to be a "retail" price substantially higher than the 
negotiated discount prices which large institutions pay. 


***** Protease Inhibitors: Ritonavir and Saquinavir 
Combination Trial Recruiting -- Seven U.S., Canada Sites 
Including San Francisco

The first trial to combine protease inhibitors is now 
recruiting 120 volunteers in seven sites in the U.S. and 
Canada. This study is being conducted by Abbott Laboratories, 
Inc.

There is much interest in combining these two drugs, for 
several reasons -- but there are also potentially serious 
safety concerns. Saquinavir is quickly eliminated from the 
body, making it hard to get sufficient blood levels with the 
currently approved drug formulation; ritonavir, given with 
saquinavir, can produce increased and sustained levels of 
saquinavir because it slows the process used by the body to 
eliminate saquinavir. Also, the drugs have very different 
resistance patterns, which may work together well to slow the 
development of viral resistance to the combination.

But this combination must be tested very carefully. Correct 
dosing must be used when combining these drugs -- and the 
doses are not yet known. Blood levels of saquinavir become 
higher than previously achieved, and the safety of saquinavir 
at these blood levels is unknown. In addition, if doses are 
too low, viral resistance could develop. To help avoid these 
problems, blood levels will be measured in this trial, using 
a test which is not commercially available.

To be eligible, you must be at least 12 years old, have a CD4 
count of 100 to 500, have never taken any protease inhibitor, 
have no acute opportunistic infection nor inflammation of the 
pancreas, and not be taking any medication contraindicated 
with ritonavir. You can be using other approved 
antiretrovirals (AZT, etc.), but will have to stop them two 
weeks before beginning treatment in this trial.

For more information about these trials, call Mabrey Whigham 
at the International Association of Physicians in AIDS Care, 
312/419-7295. Or for the San Francisco trial, you could call 
the HIV Institute at Davies Medical Center, 415/565-6222. We 
could not determine the other cities before going to press.


***** Protease Inhibitors: Background Information

One of the best information sources on protease inhibitors 
continues to be the National AIDS Treatment Advocacy Project 
(NATAP). You can obtain its written report, get the most 
current information from its Web site, or obtain videotapes 
of two major community meetings which NATAP has held so far, 
in New York (January 26) and Los Angeles (April 13).

* To obtain HIV PROTEASE INHIBITOR REPORT (Second Edition-
3/96), by Henry E. Chang and Jules Levin, contact NATAP, 72 
Orange Street, #3C, Brooklyn, NY 11201, phone 718/624-8541, 
fax 718/624-8399. Please do not phone or fax late at night.

* If you can use the World Wide Web, you can get additional 
information at http://www.aidsnyc.org/natap.

* The entire 4-hour Los Angeles symposium is available on 
videotape -- $35 for individuals, $100 for professionals 
(doctors, hospitals, corporations, etc.), free or sliding 
scale for individuals who cannot afford to pay. You can order 
it from NATAP at the above address.

Los Angeles Meeting

About 700 people -- apparently a record for any AIDS medical 
meeting in Los Angeles -- filled the Paramount Pictures 
Theater on a Saturday afternoon, April 13, for "Protease 
Inhibitors: Current and Future Use," a free educational forum 
organized by Jules Levin of NATAP, along with over 15 Los 
Angeles AIDS organizations. The theater was still full three 
hours after the program started.

Perhaps the most important theme of the Los Angeles meeting 
was the need to follow medical advice and use these drugs 
properly. "Drug holidays," arbitrary dose reductions, and 
other misuse create windows of opportunity which can help the 
virus become resistant to the drugs. Once resistance 
develops, it is probably permanent, and one or more of the 
protease inhibitors will be less valuable to the patient in 
the future.

Note that some protease inhibitors must be taken on a full 
stomach, and others on an empty stomach, to be absorbed 
effectively. Physicians can give instructions on what is and 
what is not acceptable.

For persons beginning treatment with the Abbott protease 
inhibitor ritonavir (Norvir(TM)), Abbott is recommending a 
dosage ramp-up approach, in which slightly lower doses may be 
used for the first few days. This dose adjustment may help 
the body adapt to ritonavir by gradually introducing the drug 
into the blood. It may reduce unpleasant side effects which 
some (though not all) patients experience, especially during 
the first two weeks. Abbott does not expect this approach to 
increase drug resistance.

It is essential to follow medical advice about not combining 
the Abbott protease inhibitor with many other common drugs. 
Some of these drugs can cause life-threatening reactions if 
combined with ritonavir.

There are fewer side effects and drug interaction problems 
with the other two approved protease inhibitors, indinavir 
(Crixivan) and saquinavir (Invirase(TM)). But interaction and 
other safety precautions must be followed with these drugs 
too.

Meeting Organizers Note

Persons organizing AIDS meetings should note some of the 
factors which led to the large attendance of the protease 
inhibitor symposium in Los Angeles, a city where people are 
unlikely to come to AIDS meetings. (1) The topic was urgently 
important, as many people are starting these drugs and need 
information. (2) The symposium had very good support from 
local AIDS organizations, some of which mailed the flyer to 
their clients. (3) Volunteers carried flyers to HIV medical 
practices and clinics, coffeehouses and bookstores, and other 
appropriate locations. (4) Meeting organizer Jules Levin came 
to Los Angeles several days in advance to work full time on 
the arrangements.


***** Delavirdine Available on Expanded Access

Persons with a CD4 count of 300 or less who are failing other 
therapy may qualify for an open-label program to use the 
experimental antiretroviral delavirdine in combination with 
at least one other antiretroviral.

To be eligible, patients must not be hospitalized, or have 
"an acute, serious, life-threatening condition," or be 
treated concurrently with rifampin, rifabutin, astemizole, 
loratidine, or terfenidine. Patients must not have hemoglobin 
less than 8.0, neutrophils less than 600, platelets less than 
25,000, or creatinine greater than 3.0. There are some 
additional entry criteria.

Your physician can register you for the program by calling 
800/779-0070. Some paperwork will be required, and possibly 
local IRB approval. This program has already been approved by 
a national IRB.

For more information, persons in the U.S. and Canada can call 
800/432-4702 or 800/779-0070.


***** Sinusitis: Helpful Background, Treatment Article

A useful background article on sinusitis was published in the 
March 1996 issue of BETA (BULLETIN OF EXPERIMENTAL TREATMENT 
FOR AIDS), a treatment newsletter published by the San 
Francisco AIDS Foundation. "Sinusitis," by Leslie Hanna of 
the Foundation, looks at causes, symptoms and diagnosis, and 
various different antibiotic and other treatments -- 
including acupuncture, herbal treatments and holistic 
interventions.

San Francisco residents may pick up a free copy of BETA at 
the San Francisco AIDS Foundation, 10 UN Plaza, at the Client 
Services Waiting Room on the 2nd floor. Others may call BETA 
at 415/487-8060 to get a copy or a reprint.

Subscriptions to BETA cost $75 (institutional rate $165), and 
can be ordered by calling 800/959-1059.


***** Chinese Medicine: Qigong Exercise Tape Available

For several years Emilio Gonzalez and George Wedemeyer have 
been leading classes in Qigong, a form of exercise used in 
traditional Chinese medicine. The classes, for people with 
HIV or other chronic diseases, request a nominal donation of 
$1. Now the instructors, both long-term AIDS survivors, have 
produced a four-week Qigong class on videotape, with help 
from video professionals who volunteered for this project. 
All proceeds from the sale of the tape will support direct 
client services at the Immune Enhancement Project (IEP), an 
acupuncture clinic in San Francisco. (For an interview with 
Tom Sinclair, L.Ac., executive director of the Immune 
Enhancement Project, see AIDS TREATMENT NEWS #230, September 
1, 1995.)

The two-tape set, with four lessons totaling two and a half 
hours, can be ordered for $59.95 from the Immune Enhancement 
Project, 3450 16th St., San Francisco, California 94114, 
800/835-6555 or 415/252-8711, fax 415/252-8710.

For more information about the San Francisco classes, call 
George Wedemeyer, 415/975-4561 or Emilio Gonzalez, 415/255-
0265. Or check the IEP home page on the World Wide Web, 
http://www.creative.net/~iep -- which also includes a form 
for ordering the tape by fax.


***** rGP-160 Treatment Vaccine (VaxSyn): Canadian Study 
Finds No Benefit

A multi-center trial in Canada, which gave either recombinant 
GP-160 or placebo to 278 volunteers with HIV during a three-
year study, found "no clinical benefit from this product nor 
any usefulness in maintaining immune competence," according 
to Chris Tsoukas, M.D., of Montreal General Hospital. Dr. 
Tsoukas noted that these results do not apply to preventive 
vaccine trials.

The Canadian study was completed in November 1995, but the 
results were not announced until a similar U.S. study was 
completed in March.

Only a brief announcement of the negative finding has been 
made at this time. Detailed results may be available in a few 
weeks.

Comment

This negative result illustrates the need for research in HIV 
pathogenesis, and particularly in the correlates of immunity. 
It is easy to produce an antibody response, or other kinds of 
immune response to HIV. What is much harder is to know what 
kinds of immune response are protective.

While difficult, this problem is not impossible. Studies of 
long-term nonprogressors (who have HIV but do not get sick), 
and of persons who have been repeatedly exposed to HIV and 
remained uninfected, may help to determine what kinds of 
immunity are effective in preventing or controlling 
infection.


***** FDA Reform in Congress: Interview with
Peter Barton Hutt

by John S. James

Legislation to change the U.S. Food and Drug Administration 
has now been introduced in both houses of Congress. This 
legislation might become law, and interested parties need to 
make themselves heard now, as Congress must act quickly on 
these bills, or it will be too late for this year. Those who 
are not aware of the issues involved could miss the chance to 
have a say in decisions affecting them.

For one view on these issues, AIDS TREATMENT NEWS interviewed 
Peter Barton Hutt, who is widely recognized as one of the 
world's leading experts on FDA law. Mr. Hutt has practiced 
regulatory law for the past 35 years, and served as general 
counsel of the FDA between 1971 and 1975. He is now in 
private practice at the Washington D.C. law firm of Covington 
and Burling, and also teaches a course in food and drug law 
at Harvard Law School.

We told Mr. Hutt that we were especially interested in the 
earlier stages of the drug development process, as well as in 
the current legislation.

AIDS TREATMENT NEWS: Some people are saying that the rapid 
approval of protease inhibitors shows that FDA reform 
legislation is not needed, that any problems have already 
been fixed. What else should these people be aware of?

Hutt: The rapid approval of a number of new drugs shows that 
where FDA wishes to do so, it can place its resources and can 
improve the system. The difficulty is that those cases 
represent ad hoc decisions under a great deal of pressure at 
one particular point in time, and do not represent a 
systematic change in FDA procedures and policies. One cannot 
conclude that these improvements will apply for a longer time 
to a wider group of therapies.

The drug approval process cannot be viewed in isolation. It 
is part of an extraordinary lengthy discovery, research, and 
development process that now takes more than a decade. Only 
20 years ago, the process from drug discovery to approval 
averaged approximately six to at most eight years. Today it 
is in the area of 15 to 16 years. The time required has 
roughly doubled during the last two decades.

What has happened is that the FDA has become more stringent 
overall in its requirements. While the time for APPROVAL has 
remained the same or diminished slightly, the time for 
research and development has escalated dramatically, making 
it take even longer for important new products to reach the 
marketplace. Therefore, in looking at legislation, one must 
focus on all aspects of this process, not only on the final 
decision of approval or disapproval.

ATN: Where in the earlier phases do you think major time 
savings can and should be made?

Hutt: They must be made in every stage. The first stage is 
preclinical testing. FDA has requirements that must be met 
before any drug can be put into a human. These have been 
relatively stringent and relatively inflexible. If they are 
made less stringent and more flexible, human trials could 
start more rapidly.

Second, one must look at the requirements FDA has imposed for 
submission of an IND application. [Note: An IND -- 
Investigational New Drug -- application must be approved by 
the FDA before a new drug can be tested in humans.] If you 
compare the size and content of an IND in the United States 
and in Europe, you will see that the one in the United States 
can be six or eight feet thick, and the one in Europe is six 
or eight inches. That difference represents an enormous 
investment of time, resources, and of course money. In Europe 
you can investigate more drugs than in the United States, 
because the investment required is less.

Third, when you look at the requirements for monitoring and 
record keeping, and adverse reaction reporting, in Europe vs. 
the United States, you understand why more and more clinical 
trials are being conducted abroad. You can do much more for 
less money, more quickly and more efficiently, abroad than 
you can in the United States. The consequence is that some 
investigational drugs which are available abroad cannot be 
used for any form of expanded access or compassionate use in 
this country.

ATN: The cost of new AIDS drugs is now a major issue. Could 
we reduce drug prices by cutting the cost of development?

Hutt: Time is money. The amount of resources needed to 
investigate and ultimately bring to approval a new drug 
depends on time, and also on the complexity of the 
requirements imposed. Regulatory requirements therefore 
directly decide the ultimate price of a drug.

ATN: Someone described the current "Good Laboratory Practice" 
regulations as 40 tons of cure imposed because of isolated 
instances of abuse.

Hutt: One company submitted fraudulent data on its testing of 
pesticides and other products. As a result, FDA imposed, in 
the late 1970s, stringent Good Laboratory Practice record 
keeping requirements that are enormously costly and 
burdensome.

Every bit of this contributes to cost and time. The 
difficulty is that, if you take any one of these issues in 
isolation, you can find some justification for it. In 
isolation, you can say, "That only costs so much more." But 
if you put them all together -- and consider that they have 
been added one on top of the other for the last 40 years -- 
you begin to understand the enormous impact.

ATN: How do the bills in Congress now address these problems? 
[Note: The bills referred to in the following discussion are 
S. 1477, introduced by Senator Nancy Kassebaum, Republican, 
Kansas, on December 13, 1995, and H.R. 3199, introduced in 
the House by Congressman Richard Burr, Republican, North 
Carolina, on March 29, 1996.]

Hutt: These bills are remarkably close in philosophy and 
intent. They are written with different words and phrases, 
but that should not be interpreted as meaning a fundamentally 
or structurally different approach. They are very similar.

ATN: We reported to our readers when a draft of the Kassebaum 
bill became available (see AIDS TREATMENT NEWS #235, November 
17, 1995) that this bill focuses on procedures to hold the 
FDA accountable for its performance, rather than on mandating 
or micromanaging specific decisions.

Hutt: The same concept occurs in the House bill. That is why 
I said they are similar in concept. Both bills realized that 
you cannot focus on just one part of the total discovery, 
research, development, and approval process. You have to deal 
with every aspect of that or you will not make a difference.

Each bill has its strength and weaknesses. Let me mention one 
difference which is important, and may be misunderstood.

The Senate bill contains a provision, a strongly worded 
statement of philosophy, which says that any patient, through 
a physician, has the right to request an investigational drug 
for expanded access treatment use, and any company has the 
right to provide that. The company does not have an 
obligation to provide it, but they have the right to do so. 
That statement does not occur in the House bill, but the 
House bill clearly provides, without saying it, that the same 
is true.

My personal preference would be to include this explicitly in 
the legislation. But it is erroneous to think that the House 
does not agree with expanded access because it did not 
include this specific language. I would certainly support an 
explicit provision of that kind, which gives a flavor, tone, 
or mandate that otherwise might not be clearly understood.

ATN: But it does not create a new legal right?

Hutt: It is legally unenforceable in both bills, but it is 
nonetheless a very powerful statement of intent.

ATN: But you think that patient advocates might want to make 
it clear to Congress that they want the Kassebaum version to 
prevail in the final legislation?

Hutt: Yes. I believe interested people should make clear to 
the House that they consider immediately incorporating it 
into the next version of the bill.

ATN: And they could copy the language right out of the 
Kassebaum bill?

Hutt: Yes. The language in the Kassebaum bill to my knowledge 
has not been substantially opposed by anyone -- not by 
patient groups, not by the industry, not by consumer 
advocates, not by anyone. It may have been omitted from the 
House bill only because nobody lobbied the House on it.

Hutt: There is another important provision in the Senate bill 
that your readers should be aware of, and come to their own 
decision. Under current FDA regulations, for a drug treatment 
IND and for all medical devices, a company is permitted to 
charge for an investigational product. They can charge for 
the manufacture of the drug, for the cost of research and 
development, and for the cost of handling. Under the Senate 
bill, the cost of research and development was deleted.

The first question is, what does that mean? Will the FDA have 
to delete the cost of research and development from the 
treatment IND and medical device regulations? I do not 
believe that is what is intended, but the meaning is quite 
unclear. The second question is why was that provision 
deleted, who deleted it, and what was the intent of the 
Committee? That is unclear to me as well.

If in fact it means that companies would be completely 
prohibited from taking into account their research and 
development costs in charging for investigational products, 
it seems to me highly probably that far fewer companies would 
be willing to make investigational products available. They 
would be lucky to break even. Considering the time and effort 
it takes them to provide expanded access, it would 
undoubtedly not be worth their effort. In my judgment, this 
change would substantially reduce the number of 
investigational products available for expanded assess. 
People should consider this issue, and whatever their views 
are, make them known to both the Senate and the House. There 
is no comparable provision in the House bill.

ATN: What is the timetable for this FDA legislation?

Hutt: The timetable in Congress is tight. There are 
relatively few legislative days left in Congress this 
session. Senator Dole, on the campaign trail, did commit to 
bring this bill to the floor in the Senate, so it is likely 
that will happen.

ATN: Is Kennedy likely to oppose the bill, or not?

Hutt: The position of Senator Kennedy remains unclear. He 
voted against the bill in the Senate markup, but three 
Democrats voted for it. There are attempts to achieve 
compromise to make it less likely that he will oppose it. It 
is entirely uncertain what his ultimate position will be.

ATN: Is Kennedy concerned about allowing pharmaceutical 
companies to talk about off label uses of drugs?

Hutt: That provision was deleted from the Senate bill in the 
markup, because the Committee could not reach a consensus on 
exactly what it should say. There are efforts now to reach a 
compromise and put that provision back into the bill.

ATN: What are Kennedy's main objections at this point?

Hutt: That is a very long story. It appears that every time 
one of his objections is met, he comes up with a new 
objection on a different provision. There is some concern 
that there is an endless list that would gut the entire 
legislation if it were met.

ATN: Do you think the FDA wants to conduct a war of attrition 
against the bill through Senator Kennedy?

Hutt: In one syllable, yes. This is not a surprising 
strategy. The FDA is totally opposed to the entire 
legislation. There is nothing in the bill that is acceptable 
to FDA. It will do whatever it can to delay the bill or 
defeat it.

ATN: What can individuals and organizations do to get their 
views heard and considered on these issues, at this late 
time?

Hutt: People should work through their organized groups, 
which are singularly the most effective way of making their 
views known, as well as getting in touch with their own 
personal representatives in the Senate and the House. Working 
through organized groups that are in Washington, and can 
monitor the progress and the changes that are made, is always 
the most effective way to proceed.


***** FDA Reform in Congress: FDA's Concerns

by John S. James

Perhaps the best case against major elements of the FDA 
reform legislation now being considered by Congress is the 
February 21, 1996 testimony of FDA Commissioner David A. 
Kessler, M.D., before the Senate Committee on Labor and Human 
Resources -- chaired by Senator Nancy Kassebaum, Republican, 
Kansas, who introduced S. 1477. It is impossible to 
meaningfully summarize this statement, which is 48 pages 
double spaced plus 19 pages of attachments. But we want to 
give our readers a sense of some of the concerns. (Note: 
Kessler's testimony addressed only S. 1477; H.R. 3199 had not 
been introduced yet.)

Dr. Kessler urged Congress to consider the progress in rapid 
drug reviews and other areas that has been made in the past 
several years. "If we are to achieve our shared goals of 
improving the Agency's ability to protect and promote the 
public health, we must base our work on FDA's current 
performance. Unfortunately, too many of our critics justify 
the call for 'reform' based on how the FDA did its job in the 
1980s or earlier. They have missed the substantial progress 
that the dedicated doctors, nurses, engineers, chemists, 
microbiologists, biostatisticians, nutritionists and others 
at the FDA have achieved over the past several years. They 
would have us ignore the important lessons that we have 
learned about the kinds of change that will result in getting 
safe and effective drugs and devices to the market more 
quickly. Those who fail to recognize the Agency's performance 
and achievements threaten -- intentionally or not -- to 
undermine the real progress the Agency has made. Undermining 
progress in critical public health and consumer protection is 
not 'reform.'"

Dr. Kessler pointed out that according to a study by the 
General Accounting Office (GAO), the average time for 
approval of new drug applications was 33 months for 
applications submitted in 1987, but reduced to 19 months for 
those submitted in 1992. This, he noted, was largely due to 
user fees for prescription drug approvals -- a system created 
by Congress in 1992, with the approval of the pharmaceutical 
industry. Under this system, companies pay to have their 
applications processed by the FDA -- which uses the money to 
increase staff and other resources to get the applications 
handled more quickly. This system included performance goals 
for the FDA, which has already met the 1997 goal for reduced 
review time, three years ahead of schedule.

Kessler cited extensive comparisons between drug approval 
times in the U.S., the UK, Germany, and Japan -- making a 
strong case that the U.S. now has the fastest drug approvals 
of the four.

But Dr. Kessler was concerned about the requirement of S. 
1477 that by July 1998 the FDA would review all drug approval 
applications within 180 days, and priority drugs within 120 
days. "I do not believe that the Agency could meet the 
product review times set forth in S. 1477, with existing 
resources, without compromising existing public health 
protection...

"What does it take to review an application within four to 
six months? First, it takes an excellent application. With 
only four to six months there would be little opportunity to 
obtain clarifications or additional information from the 
sponsor. Although every application could be reviewed exactly 
as it is submitted, very few applications are so complete and 
accurately presented as to be approvable without further 
discussion with the sponsor. Second, it requires having the 
necessary review staff, including all the various 
disciplines, ready to work on the application the day it 
comes in the door. That means other work needs to be put on 
hold. Third, it means companies will need to be fully ready 
to manufacture the drug... Fourth, the shortened review times 
will compromise the effectiveness of advisory committees...

"Under the S. 1477 timeframes, the Agency also would be 
required to limit its involvement in the production and post-
approval areas... In fiscal 1995, there were 251 product 
recalls."

"Shortening the review times also will adversely impact 
Agency programs that are NOT related to drugs or other 
product approval process, such as the safety of the blood 
supply, food safety and tampering, and mammography quality. 
Our efforts to protect the public from unsafe imported 
products -- whether it is botulism-contaminated mushrooms or 
hepatitis-contaminated human tissue, will have to be 
curtailed. It will also severely curtail our ability to 
respond appropriately to emerging public health threats, 
crises, or even to new areas where a little work would have a 
large payoff."

Kessler outlined many other concerns:

"There are several sections of the bill that would establish 
new and lower product approval standards. For example, 
Section 407 would establish a new process for approving new 
uses of existing drugs that would completely bypass the drug 
approval process. It would establish a procedure for 
recognizing new uses based on medical practice... This 
provision moves us away from the accepted scientific standard 
of evidence back toward evidence based solely on anecdotal 
experience..."

"We are also concerned that the bill would eliminate FDA's 
role in assuring that modifications made to a product do not 
adversely affect its safety and effectiveness. Under the 
bill, unless the manufacturer's own data show that safety and 
effectiveness were to diminish, FDA could not require data on 
the modified product (Sections 702 and 707). Yet we know that 
such modifications can carry initially unrecognized risk..."

"We are equally concerned that the bill would remove even the 
basic assurance that most new devices will be well made. 
Under Section 702 a company, even one with known 
manufacturing problems directly relevant to its new device, 
would have to be given marketing approval even though the 
Agency has evidence the firm is unable to produce a quality 
product..."

"There are a number of provisions throughout the bill which 
would allow companies to market products without FDA 
approval, if the Agency fails to meet review deadlines..."

"The bill's requirement for third party review is equally 
troubling... FDA's scientists and experts are charged with 
exercising independent and unbiased judgment. They comply 
with stringent financial disclosure and conflict of interest 
requirements designed to protect the decision-making process 
against bias. It is not clear whether, and how, this 
independence can be maintained with private sector review 
organizations...

"The substitution of judgment also extends to the 
manufacturing area. When a contractor has given a 
manufacturer good marks for its production process, FDA is 
prohibited from inspecting the plant for two years unless the 
Agency learns through other means that there is something 
seriously wrong at the plant." 

Other concerns involve expanded access -- now available 
through FDA regulations, which would be legislated instead, 
beyond the FDA's control:

 "Unfortunately, S. 1477 (Section 202) would permit drug and 
device companies to side-step completely FDA's approval 
process and go into the manufacture, promotion, and sales of 
a product for any serious disease or condition without FDA 
approval. Under S. 1477's provisions, expanded access 
protocols could be given for any product that diagnoses, 
monitors, or treats a serious disease or condition, so long 
as other therapy is not 'comparable or satisfactory.'

"In addition, S. 1477 would permit the manufacturer to widely 
promote the availability of the expanded-access protocol 
(Section 202). Unlike FDA's current system for cost recovery 
under a treatment IND, there is no requirement in the bill 
that adequate enrollment be obtained for clinical trials that 
are designed to determine the safety and effectiveness of the 
product, and that the manufacturer pursue marketing approval 
with due diligence. In short, the patient would have to pay 
full price for an experimental product, and the company would 
be under no obligation to ever find out its true value. 
Coupled with the provision for cost recovery, promotion of 
the availability of experimental treatments would create a 
climate where the unscrupulous could sell untested hope with 
scant risk of being found out and only weak sanctions if they 
were. The 1995 Health and Human Services Inspector General's 
review of commercialization of unapproved medical devices 
shows this is not just a theoretical risk but a predatory 
business practice hard to control even with today's stronger 
law."

Off Label Drug Information

Major controversy exists about whether pharmaceutical 
companies should be allowed to promote "off label" uses of 
approved drugs -- that is, uses which have not specifically 
been approved by the FDA. The FDA realizes that off label 
drug uses can be appropriate and beneficial. But at present, 
a pharmaceutical salesperson cannot give a physician a peer-
reviewed journal article about an unapproved use of the 
company's product, unless the physician asks for it.

Kessler did not address this issue, but left it to William B. 
Schultz, Deputy Commissioner for Policy, to present the FDA's 
position to the Senate Committee on Labor and Human 
Resources, on February 22, 1996. Schultz described a number 
of cases where allowing companies to promote off label uses 
would have led to serious harm.

We have not seen a similarly detailed case in favor of 
changing the current law. Such a document is needed, because 
this issue requires a judgment call. The examples cited by 
Schultz must be balanced against the damage caused by poorly 
informed physicians who do not read the literature or who 
find it safer for their careers to avoid initiative, and 
provide poor treatment to patients when better treatment is 
possible.

Schultz also described major FDA initiatives to reverse 
certain problems at the FDA in the past, and make it much 
easier for companies to get new indications onto the label. 
He noted that many off label uses could be approved with no 
new clinical trials, if companies would just copy existing 
data and submit them to the FDA. And the FDA is now working 
with leading physicians to identify the most important off 
label uses, in order to work with companies to get them 
approved.

Comment

Our goal in reporting the controversy about Congressionally-
mandated FDA reform has been to expose our readers to leading 
advocates of both sides, and to the complexity of the issue. 
Those who work seriously in this area will need to study and 
listen to differing views. So far the custom has been to hear 
one side, and demonize the other.

The remarkably articulate and compelling arguments on both 
sides are only a beginning to understanding in this area. On 
closer look, both leave much to be desired. Hutt addresses 
easy issues of the current legislation. Kessler addresses 
hard ones, but questions remain.

For example, it could be argued that a "climate where the 
unscrupulous could sell untested hope" might ultimately save 
many more lives than the climate we have. For excluding 
"untested hope" has also largely excluded all contributions 
except from big business -- shutting out small companies, 
which are often the most creative, but which have to sell out 
to the big ones. (It is no accident that the driving force 
behind the current FDA-reform legislation is the medical-
device industry, largely consisting of entrepreneurial 
companies far smaller than the huge corporations of the 
pharmaceutical industry.)

And also largely excluded is every medical tradition on Earth 
except for one -- the one which has developed only in the 
last several decades but has used its money to dominate 
Western institutions, especially in the U.S. This dominant 
tradition is increasingly based on formal evidence -- perhaps 
a major advantage -- but also it is notably crude, 
inefficient, narrow, and cruel in its methods of gaining 
knowledge. A better public policy might be to open the door 
somewhat wider, trusting more in the judgment of patients and 
physicians, judgment which of course includes formal evidence 
when available, but also includes other evidence not 
formalized yet. Yes, quacks will use the opening; but nothing 
eliminates quackery faster than treatments that really work. 
And it is preposterous to think that the best way to find 
treatments that work is to eliminate all of the human race 
except for the narrowest elites from any real role in medical 
development.

The most central issue, we believe -- beyond anything 
Congress does this year -- is how to make medical research 
and drug development work better. We fear that neither side 
in the politically charged debate has a useful answer. For 
decades, an FDA controlled by Democrats in Congress piled 
rule upon rule in the name of public safety, oblivious both 
to financial costs, and to the human costs of research 
stagnation. Now Republicans control Congress, and industry 
believes its day is here, and wants its reward. Both 
ideologies are a disservice to the public.

Perhaps the best we can hope for immediately is what has 
already been happening so far -- no new law, but the FDA so 
afraid of one that it does more than seemed possible to 
improve itself from within.

We believe that the key bottleneck in medical research is the 
difficulty of obtaining the first credible data in human 
testing of a new idea or approach. Senator Kassebaum's office 
chose NOT to address this issue in S. 1477 -- probably 
because the most visible proposal for doing so (letting 
institutional review boards bypass the FDA and approve human 
trials) clearly has drawbacks. No one knows how to balance 
safety and progress at the edge of creativity and the 
unknown. Perhaps there is no systematic way.

The current debate has been productive in stimulating FDA 
reform. It could be equally valuable if it shakes official 
Washington out of its traditional ignorance and disinterest 
in the obstacles to medical progress, and the opportunities 
to do better.

For More Information

* Anyone can get current copies of this (and other) current 
Federal legislation through the World Wide Web, at address 
http://thomas.loc.gov/. Search for bill numbers s1477 and 
hr3199. There is no charge for using this service, which is 
provided by the Library of Congress.

* The text of the testimony by Dr. Kessler and Mr. Schultz is 
available from the FDA Office of AIDS and Special Health 
Issues, 301/443-0104, fax 301/443-4555. On the World Wide 
Web, Dr. Kessler's talk is at 
http://www.fda.gov/ola/nktest.html. Also note the FDA home 
page, http://www.fda.gov.

* The Log Cabin Republicans, a gay political organization, is 
supportive of both S. 1477 and H.R. 3199; their views are 
often close to those of Peter Hutt. They can be reached at 
202/347-5306.

* Most AIDS organizations which have a position are opposed 
to both bills. One source of information on the opposition is 
the Patients' Coalition; call Derek Link 212/337-3502. This 
association of health groups has many concerns. Link sees the 
bills primarily as privatization -- allowing private 
companies to do inspection and other work now done by FDA 
staff.

* AIDS Action Council is working on this issue and is 
opposing both the bills. Press can contact Joe Zuniga 
202/986-1300, x3042. Others can contact Scott Sanders at the 
American Foundation for AIDS Research, 202/331-8600.


***** Vancouver Conference: Make Travel Plans Now. Focus, 
Program, and Satellite Meetings

The program of the XI International Conference on AIDS 
(Vancouver, July 7-12, 1996) has been built around the 
abstracts submitted. Since the abstract deadline was February 
1, and it took time to review and categorize the submissions, 
the major scientific issues which the conference will address 
are only now coming into view. Some of the areas which will 
receive most attention are:

* Use of combination therapies with protease inhibitors;

* Immunomodulators and malignancies;

* Ethics and methodology of clinical trials;

* Complementary therapies;

* Management of HIV infection in children;

* Resistance to antiretroviral drugs;

* The HIV life cycle;

* Viral pathogenesis;

* New research in preventive vaccines;

* Natural history and determinants of long-term non-
progression;

* Prevention of mother-to-child transmission;

* Sexually transmitted disease prevention to reduce HIV 
infection;

* Needle-exchange programs;

* Female-controlled methods to prevent HIV transmission;

* HIV and human rights;

* Community mobilization;

* Papers which seek to draw together activists, people living 
with HIV, and researchers around common interests.

A record number of abstracts -- 5,626 -- were submitted to 
this conference; this is more than for any other conference 
except Berlin, which allowed individuals to be presenting 
author for more than one abstract. About 90% of the Vancouver 
abstracts were accepted.

Plenary Program

The plenary program -- the talks and debates addressed to 
everyone at the conference -- is now as follows:

* Monday July 8: Antiviral Therapy and Viral Load; HIV 
Genetic Diversity; The Epidemic of HIV among Young Gay Men; 
and a debate on whether the prohibition of addictive drugs 
can make a significant contribution to HIV prevention and 
control.

* Tuesday July 9: Empowerment, Community Mobilization, and 
Social Change in the Face of AIDS; Perinatal Transmission; 
Female-Controlled Methods; and a debate on vaccines, whether 
more fundamental science is needed before large phase III 
vaccine trials.

* Wednesday July 10: Molecular Biology and Drug Development; 
Continuum of Care in Resource Poor Settings; HIV and 
Development; and a debate, topic not yet set.

* Thursday July 11: Positive Developments in Interventions; 
The Impact of HIV on Families and Children; HIV Viral 
Dynamics; and a debate on the relative contribution of viral 
factors vs. host factors in pathogenesis.

Travel, Media Arrangements

It is important to make travel reservations now, due to 
limited space in hotels and in flights into Vancouver.

Media persons must be accredited to cover the conference, and 
are strongly urged to take care of that now, due to limited 
hotels in Vancouver.

Contact Greg Hamara (see Contact Information, below).

Skills Building Meetings, July 8-11 Afternoons

"Managers, trainers, programmers, volunteers, and clinicians 
from developing countries are encouraged to participate with 
professional facilitators and experienced community based 
practitioners. The workshops will examine analytical tools, 
low cost technology and the experience of participants to 
find new personal and group resources for dealing with 
challenges of community based organizations."

Topics include assessing community needs, interactive 
training techniques, managing nutrition in the face of 
poverty, CD4 testing alternatives, writing a funding 
proposal, and many others.

For more information, contact Peter Gillies, Skills Building 
Coordinator, fax 604/668-3242, email pgillies@hivnet.ubc.ca, 
or wag@web.ca.

Community Forum 96, July 5-6

"Community Forum 96 is an international gathering of persons 
living with HIV/AIDS and community organization workers that 
will precede the XI International Conference on AIDS. Over a 
period of two days, this working meeting will bring together 
500 persons -- 100 from each of the five regions of the 
world..."

For more information, contact the Community Liaison 
Department of the Conference Secretariat; see contact 
information below.

Satellite Meetings

Organizations and companies have scheduled the following 
satellite programs. Because of limited space, we have only 
listed the date, the sponsoring organization, and the title 
of the meeting, to help people plan their schedule and make 
travel arrangements. Time and place of these meetings, as 
well as contact persons and phone/fax numbers, are usually 
available from the conference site on the World Wide Web, 
http://www.interchg.ubc.ca/aids11/AIDS96.html.

Friday July 5

 * The AIDS Control and Prevention (AIDSCAP) Project of 
Family Health International and the Francois-Xavier Bagnoud 
Center for Health and Human Rights of the Harvard School of 
Public Health. Status & Trends of the Global HIV/AIDS 
Pandemic (continues July 6).

 * Global AIDS Information Network. 1996 Biennial Meeting.

 * National Institute of Mental Health. Role of Families in 
Preventing and Adapting to HIV/AIDS (continues July 6 and 7).

Saturday July 6

 * Canadian Association of Nurses in AIDS Care. Nursing: 
Sustaining the Circle of Life.

 * AIDSCAP/Family Health International. Men, Women and AIDS: 
A Dialog.

 * American Medical Association. AIDS Media Briefing.

 * International Christian AIDS Network. A Faith Response to 
HIV/AIDS (continues July 7).

 * Health Canada, U.S. Centers for Disease Control and 
Prevention, U.S. National Institutes of Health, The Joint 
United Nations Program on HIV/AIDS, and Canadian Public 
Health Association. HIV Prevention Works / La Prevention du 
VIH, ca marche / La Prevencion del VIH da resultados.

 * European Commission. The European Communities' HIV/AIDS 
Program for Developing Countries Directorate-General for 
Development.

 * Janssen-Cilag, Opportunistic Fungal Infections in 
HIV/AIDS: Emerging Challenges and a New Solution.

Sunday July 7 - Friday July 12

Many additional satellite meetings could not be listed here 
due to lack of space; we will publish them in our next issue. 
We included the pre-conference meetings now because they are 
most likely to affect travel plans. The later satellite 
meetings occur on the days of the conference itself.

Contact Information

Conference Secretariat, XI International Conference on AIDS, 
11th floor, 1090 West Pender, Vancouver, British Columbia, 
Canada V6E 2N7; phone 800/780-AIDS, or 604/668-3225; fax 
604/668-3242;

email aids96@hivnet.ubc.ca; 

Web http://www.interchg.ubc.ca/aids11/AIDS96.html.

***** AIDS TREATMENT NEWS
      Published twice monthly

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   Internet: aidsnews@aidsnews.org
Editor and Publisher:
   John S. James
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   Thom Fontaine
   Denny Smith
   Tadd Tobias

Statement of Purpose:
AIDS TREATMENT NEWS reports on experimental and 
standard treatments, especially those available now. We 
interview physicians, scientists, other health 
professionals, and persons with AIDS or HIV; we also 
collect information from meetings and conferences, 
medical journals, and computer databases. Long-term 
survivors have usually tried many different treatments, 
and found combinations which work for them. AIDS 
Treatment News does not recommend particular 
therapies, but seeks to increase the options available.

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ISSN # 1052-4207 

Copyright 1996 by John S. James.  Permission granted for 
noncommercial reproduction, provided that our address 
and phone number are included if more than short 
quotations are used.

