|
New Guide to Living with
HIV Infection
Medical Marijuana: Alternatives
Available |
CONTENTS:
New Guide
to Living with HIV Infection
Medical
Marijuana: Largest Provider Closed, Some Alternatives Available
Medical Marijuana Distribution
Summit, Sacramento: Video Available
Efavirenz
(Sustiva(TM), DMP 266) and Saquinavir (Fortovase(R)) Combination: Pharmacologic
Interaction
If You
Are Exposed to HIV: Guidelines Published for Postexposure Prevention
Medical
Marijuana Study in San Francisco: Pays $1000, 25 Days in Hospital
Acetylcarnitine
and Neuropathy: Call for Information
Prison
or Discharge Treatment Programs: Funding Available, Proposals Due June
29
Correction:
Hepatitis C Trial
Email
Experts; Librarians: AIDS TREATMENT NEWS Seeks Expert Advice
Prospective
Case Series in Clinical Trial Design--Proposal, and NTZ Example
New GUIDE
TO LIVING WITH HIV INFECTION
One of the best general resource
books for persons with HIV is THE GUIDE TO LIVING WITH HIV INFECTION, by
John G. Bartlett, M.D. and Ann K. Finkbeiner, developed at the Johns Hopkins
AIDS Clinic and published by Johns Hopkins University Press. The revised
fourth edition is now available.
This book focuses on the
many practical concerns (not only medical ones) that a person with HIV
may face. Topics include emotional issues (anger, energy, depression, hope,
and others)--interpersonal situations (such as disclosure about one's diagnosis),
understanding how medical care is organized and some of the barriers to
access, including insurance issues--the need to have an HIV specialist
involved in one's care--hospital administration procedures--patients' rights--
finding support, and taking control of your life--and others. There are
discussions on caring for your health, medical symptoms, laboratory tests,
considering clinical trials, considering alternative treatments, and some
of the major drugs used in the treatment of HIV infection. However, this
book does not include in-depth discussion of specific antiretroviral treatments
and strategies, since these change rapidly and the information would soon
become obsolete.
If you read the "Prologue:
To People with HIV Infection and to Their Caregivers," be aware that it
is a speech given ten years ago about one person's experience with AIDS.
Readers new to this area could be confused if they miss the date in the
fine print. THE GUIDE TO LIVING WITH HIV INFECTION, 4TH EDITION IS available
in bookstores for $15.95 (paperback), or can be ordered directly from Johns
Hopkins University Press by calling 800-537-5487, Monday through Friday
8:30 a.m. to 5:00 p.m.
Medical
Marijuana: Largest Provider Closed, Some Alternatives Available
By John S. James
San Francisco's largest medical
marijuana buyers' club, the Cannabis Healing Center, was shut down on May
25 due to a court order obtained by state Attorney General Dan Lungren--
creating an emergency for thousands of persons with serious illnesses who
were obtaining marijuana from the Center and are unable to get relief from
any other treatment.
City officials are exploring
ways to help patients obtain marijuana legally when it is medically recommended
by their physicians. Meanwhile, three smaller buyers' clubs remain open
in San Francisco, and there are others elsewhere in the state--although
these will not be able to meet the needs of everyone, due to limited staff
and the intensive checking of documentation required.
The three in San Francisco
differ in their documentation requirements and their services:
ACT UP/San Francisco, 864-6686,
may accept an identification card from the Cannabis Healing Center or Flower
Therapy (another medical marijuana group forced to close in San Francisco).
Otherwise it requires a letter of diagnosis and a state identification
(such as a driver's license)
C.H.A.M.P. (Cannabis
Helping Alleviate Medical Problems), 861-1040, is the only remaining center
in San Francisco that offers a space where patients can socialize with
each other and smoke cannabis there if they wish. C.H.A.M.P. requires a
physician's letter written within the last 30 days which states the illness
diagnosed and which either recommends or approves cannabis for the illness,
and states that the physician will continue to monitor the patient; a form
letter is available from C.H.A.M.P. Identification can be a current California
drivers license or ID, passport, or SSI letter.
Market Street Club, 861-1864,
requires a photo identification by a state or Federal agency--for example,
a drivers license, passport, or military ID; it also requires a letter
of diagnosis, and letter of recommendation, by a medical doctor. A patient
can bring the same letters they used at clubs that have closed, even if
on the other club's stationery. Documentation must be the original (not
a photocopy); the club will make copies for its records and return the
originals.
Also nearby is the Oakland
Cannabis Buyers' Cooperative, 510-832-5346. It requires a physician's letter
of recommendation (within the last six months) that can be verified, and
a current identification.
On June 1 the San Francisco
Board of Supervisors passed a resolution urging the city attorney, with
the district attorney, to draft legislation for emergency distribution
of medical marijuana. The goal is to develop a system that will have the
best possible chance to withstand legal challenge, and especially to minimize
legal liability of city employees. Even if everything goes well, it will
probably take two months or more for any new system to be set up.
Comment
San Francisco health, law
enforcement, and other departments have been working for months on guidelines
for medical marijuana, consistent with California Proposition 215 (see
text below). Proposition 215 does not override Federal laws against marijuana,
but in practice Federal authorities usually leave marijuana enforcement
to state or local jurisdictions, unless large quantities are involved.
We hope that official guidelines
or supervised distribution systems will make provisions for patients and
their caregivers to grow their own marijuana if they choose, as they are
allowed to do under Proposition 215—including growing collectively in a
community garden for those unable to do so at home. Then the price could
be reduced to about the cost of garden tools and fertilizer. This is important
because many patients are already under severe financial pressure because
of their illness.
Also, there is an urgent
need for organizations which will consistently help patients to tell their
personal stories-- for example, providing professional video feed to national
news media, and referring reporters to patients willing to be interviewed..
Election Note
California Attorney General
Lungren's closure of the Cannabis Healing Center also shut the campaign
office of Dennis Peron, who had founded the previous Cannabis Buyers' Club
at that site and was running for governor against Lungren in the Republican
primary on June 2. Peron's staff was later given a few hours to remove
their campaign equipment and materials. Many phone calls in the critical
get-out-the-vote week before the election were unable to get through.
Medical Marijuana Distribution
Summit, Sacramento:
Video Available
On May 26 we attended the
Medical Marijuana Distribution Summit, a three-hour hearing by the California
Senate Committee on Public Safety, chaired by Senator John Vasconcellos.
Over a dozen doctors, law enforcement officials, political representatives,
activists, and other experts were invited to speak, and anyone could sign
up for public comment. A videotape of the meeting, available at low cost,
provides an excellent background on many of the issues today.
Unfortunately the Federal
government refused to participate, citing ongoing litigation. California
Attorney General Dan Lungren did send a representative. It is impossible
to summarize such a meeting, but here are a few things we learned:
* There are many different kinds of medical marijuana clubs. For example,
some establish a cooperative garden so that the cannabis is provided for
the nominal cost of tools and supplies--and do not make the patient wait
the months required for their plants to mature.
Models with local government
involvement include the cities of Arcata and West Hollywood. In both cities,
cannabis is grown openly for patients, avoiding the need to obtain an underground
supply.
The county of San Mateo is
exploring the possibility of a clinical trial of medical marijuana--which
could be permitted under Federal law, since the drug would be used for
research.
In some rural areas of California,
most of the interest in cannabis is not from persons with HIV, but from
patients in wheelchairs who have severe, chronic pain and have not found
satisfactory relief with other treatments. They frequently talk about suicide,
and sometimes do kill themselves. [The main problem here may be improper
pain treatment with approved prescription drugs. Experts agree and have
said for decades that severe pain is greatly undertreated. This situation
persists, in large part because doctors are afraid that they may be targeted
by law enforcement if they prescribe more pain medication. Undertreatment
of pain could be worse in rural areas where physicians may be less able
to put together a legal defense if necessary.]
* There is strong opposition
against allowing patients to use marijuana at a site were it is dispensed;
they must take it away and use it elsewhere, like other medicine purchased
at a pharmacy. [This is unfortunate since social isolation is a major problem
for patients with chronic illness and severe pain, and the social outlet
has been important where it has been tried. Many people were offended by
the "party atmosphere" at Peron's clubs; we would urge that seriously ill
patients be permitted to choose the atmosphere that works best for them.
But most cannabis clubs have had to accept the pharmacy-only model in order
to have any chance of being allowed to operate at all.]
* In most of California,
Proposition 215 has not been allowed to work, and patients are still arrested
for legitimate medical use. Some rural counties are so poor that county
workers may not get their paychecks; the funding they do have available
is from Federal marijuana-eradication projects. This dependence complicates
efforts to discuss medical use with law enforcement, and sometimes even
in local newspapers.
"California now has 20 times
as many marijuana prisoners as in 1980," according to Dale Gieringer of
California NORML (http://www.norml.org/canorml,
or 415-563-5858). Persons using cannabis for medical purposes do get caught
up in this massive arrest and imprisonment.
It is widely agreed that
Federal cooperation is necessary for finding a workable solution on medical
marijuana. But with both Democrats and Republicans using the war on drugs
as a political football, Washington has no interest in a solution at this
time.
For a Videotape of the Summit
To obtain a videotape of
the Medical Marijuana Distribution Summit, send a request to:
Attention: Claudia
Senate Rules Committee
1020 N. St., Room 585
Sacramento, CA 95814
Ask for the three-tape set
for the
"Medical Marijuana Distribution
Summit, Senate Committee on Public Safety,
May 26, 1998," and enclose
a check for $18.
Most orders are filled within
a few days.
If you have questions, callTelevising
the Senate, 916-445-4913.
Appendix: Text of Proposition
215
The following proposition
was approved by California voters in November 1996. Previous legislation
to prevent prosecution of patients had been passed by the state legislature
but repeatedly vetoed by Governor Pete Wilson, in 1994 and 1995. The governor
cannot veto a proposition passed by the voters.
SECTION 1. Section 11362.5
is added to the Health and Safety Code, to read:
11362.5. (a) This section
shall be known and may be cited as the Compassionate Use Act of 1996.
(b)(1) The people of the
State of California hereby find and declare that the purposes of the Compassionate
Use Act of 1996 are as follows:
To ensure that seriously
ill Californians have the right to obtain and use marijuana for medical
purposes where that medical use is deemed appropriate and has been recommended
by a physician who has determined that the person's health would benefit
from the use of marijuana in the treatment of cancer, anorexia, AIDS, chronic
pain, spasticity, glaucoma, arthritis, migraine, or any other illness for
which marijuana provides relief.
To ensure that patients and
their primary caregivers who obtain and use marijuana for medical purposes
upon the recommendation of a physician are not subject to criminal prosecution
or sanction. To encourage the federal and state governments to implement
a plan to provide for the safe and affordable distribution of marijuana
to all patients in medical need of marijuana.
(2) Nothing in this section
shall be construed to supersede legislation prohibiting persons from engaging
in conduct that endangers others, nor to condone the diversion of marijuana
for nonmedical purposes.
(c) Notwithstanding any other
provision of law, no physician in this state shall be punished, or denied
any right or privilege, for having recommended marijuana to a patient for
medical purposes.
(d) Section 11357, relating
to the possession of marijuana, and Section 11358, relating to the cultivation
of marijuana, shall not apply to a patient, or to a patient's primary caregiver,
who possesses or cultivates marijuana for t e personal medical purposes
of the patient upon the written or oral recommendation or approval of a
physician.
(e) For the purposes of this
section, "primary caregiver" means the individual designated by the person
exempted under this section who has consistently assumed responsibility
for the housing, health, or safety of that person.
SEC. 2. If any provision
of this measure or the application thereof to any person or circumstance
is held invalid, that invalidity shall not affect other provisions or applications
of the measure that can be given effect without the invalid provision or
application, and to this end the provisions of this measure are severable.
Efavirenz
(Sustiva(TM)) and Saquinavir (Fortovase(R)) Combination: Pharmacologic
Interaction
Anyone taking both efavirenz
and saquinavir should know that the combination can reduce the plasma level
of saquinavir by about 60%--which will likely result in underdosing of
the protease inhibitor. DuPont Merck (soon to be called DuPont Pharmaceuticals),
the maker of efavirenz, "strongly urges patients taking Sustiva with Fortovase
to talk to their physicians about changing their regimens."
Currently efavirenz is not
marketed but is available through clinical trials or through an expanded
access program. The company has sent detailed information to physicians
in those programs.
If
You Are Exposed to HIV: Guidelines Published for Postexposure Prevention
On May 15, 1998 the U.S.
Centers for Disease Control and Prevention (CDC) published guidelines for
preventive treatment of healthcare workers accidentally exposed to HIV
(for example, by being stuck with a contaminated needle). While these official
guidelines do not discuss persons exposed through sex or sharing needles,
many experts agree that the situations are similar and the same preventive
treatment should be used.
The new guidelines call for
four weeks of treatment, with either two drugs (AZT plus 3TC) or three
drugs (AZT plus 3TC, plus either indinavir or nelfinavir). Whether to use
two drugs or three--or no treatment at all--depends on the seriousness
of the exposure. The guidelines include a procedure for deciding what prophylaxis
is needed.
Treatment to prevent infection
must be started as soon as possible, preferably within a few hours of exposure,
certainly before 24-36 hours, since animal studies suggest that later treatment
might not prevent infection When starting drugs immediately is not possible,
the guidelines still recommend a later start in some situations, since
very early treatment of HIV may be beneficial, even if it is too late to
prevent the infection.
For advice in managing postexposure
prophylaxis, clinicians should consult local HIV experts, or call the National
Clinicians' Postexposure Hotline, 888-448-4911.
References
Public Health Service Guidelines
for the Management of Health-Care Worker Exposures to HIV and Recommendations
for Postexposure Prophylaxis. MMWR RECOMMENDATIONS AND REPORTS, May 15,
1998; volume 47, number RR-7, pages 1-33.
This publication is available
at http://www.cdc.gov/epo/mmwr/mmwr_rr.html;
or single copies may be obtained from the Centers for Disease Control and
Prevention, National AIDS Clearinghouse, P.O. Box 6003, Rockville, MD 20850,
telephone 800-458-5231.
It is also available by
Faxback; have the phone number of a Fax machine handy, and then call 800-458-5231
and select the faxback option, which is available 24 hours a day. You can
ask for a catalog of dozens of different documents, or get the postexposure
prophylaxis recommendations by ordering document #3003.
Also see discussion of postexposure
prophylaxis on various AIDS Web sites, including the Center for AIDS Prevention
Studies (http://www.caps.ucsf.edu/PEP.html)
or the Stop AIDS Project
(http://www.stopaids.org/morepep.html).
San Francisco has a post-exposure
prevention (PEP) study, which runs a 24-hour information line at 415-502-5PEP.
Medical
Marijuana Study in San Francisco: Pays $1000, 25 Days in Hospital
An important medical marijuana
study now recruiting will pay $1000 to volunteers who meet the entry criteria
and successfully complete the trial. The main drawback is that you must
spend 25 days in a research ward at San Francisco General Hospital--without
leaving during that time, and without receiving visitors (due to Federal
rules for studying marijuana). You can make unlimited phone calls, have
access to a TV and VCR, use the Web, and bring books and a laptop computer.
Volunteers will be randomly
assigned to either smoke marijuana cigarettes (4% THC) three times a day,
take dronabinol (Marinol) capsules (2.5 mg) three times a day, or take
placebo capsules. There is a one-third chance of being assigned to each
group.
"Our main goal is to find
out what is safe for HIV/AIDS patients," said principal investigator Donald
Abrams, M.D., professor of medicine at the University of California San
Francisco (UCSF), who has fought for years to get Federal permission to
study marijuana. "We know many patients use marijuana to relieve nausea
and loss of appetite brought on by the disease and its treatments, but
we don't know how THC- -the active ingredient in marijuana--interacts with
HIV drug therapies. For example, protease inhibitors like indinavir and
nelfinavir are metabolized by the liver, as is THC. We want to see if THC
alters the metabolism of protease inhibitors and therefore changes the
concentration of the drug in the blood, either creating a level that is
too high, producing toxicities, or is too low, rendering the protease
inhibitor ineffective."
The study will also look for any effect of marijuana on viral load, the
immune system, testosterone levels, appetite, energy intake, resting energy
expenditure, body composition, and body weight.
This study is funded by a
grant from the U.S. National Institutes of Health. Besides Dr. Abrams,
other researchers are: Morris Schambelan, M.D., UCSF professor of medicine;
Kathleen Mulligan, Ph.D., UCSF assistant professor of medicine; Neal Benowitz,
M.D., UCSF professor of medicine and pharmacology; Francesca Aweeka, Pharm.D.,
UCSF clinical pharmacist; Joseph M. McCune, M.D., Ph.D., UCSF associate
professor of medicine; Joan Hilton, Sc.D., M.P.H., UCSF assistant professor
of biostatistics/epidemiology; Tarek Elbeik, Ph.D., UCSF assistant researcher/medicine;
Roz Leiser, R.N., Community Consortium study coordinator; and Thomas Mitchell,
M.P.H., Community Consortium program director.
To be eligible, you must:
be HIV-positive and taking
either indinavir or nelfinavir and no additional protease inhibitors (other
antiretrovirals are OK);
* Have a stable viral load
and have been on stable antiviral medicines for at least eight weeks;
Have used marijuana previously
(at least six times in your life);
* Be willing to *not* use
marijuana for up to three months;
Not have active opportunistic
infections or malignancies requiring acute treatment;
* Not have had unintentional
weight loss of greater than 10% in the last six months;
Not be a tobacco smoker (currently
or within the last 30 days), be dependent on any recreational drugs, be
on methadone maintenance;
* Not be pregnant;
Meet certain other medical
conditions.
For more information about
volunteering for this trial, call the
Community Consortium THC
Study at 415-502-5705.
Acetylcarnitine
and Neuropathy:
Call for Information
Over a year ago we published
a call for information about acetylcarnitine--a substance available from
health-food stores, and also in clinical trials as a possible treatment
for diabetic neuropathy (AIDS TREATMENT NEWS #267, March 21, 1997). At
that time there was very little experience to report, since interest in
the HIV community was so new. We did not hear from anyone who believed
that acetylcarnitine either did or did not work for them.
We would appreciate hearing
from persons with HIV who have used acetylcarnitine for any purpose, either
with or without success; this information may be useful in helping to design
a clinical trial. Contact John S. James, AIDS Treatment News, 415-255-6259,
or jjames@aidsnews.org.
Prison
or Discharge Treatment Programs:
Funding Available, Proposals
Due June 29
Glaxo Welcome has issued
a nationwide request for proposal "to fund innovative programs in
which incarcerated persons with HIV are linked to treatment programs while
in prison or upon discharge." Grant sizes are expected to range from $10,000
to $50,000. These grants can be for new or existing/ongoing projects, in
any geographic location in the U. S.
Proposals are due June 29;
however, the application process is much simpler than for most grants.
The application requires only a three to five page letter (including a
description of the project and a description of the organization), with
a copy of the organization's 501(c)(3) letter of determination attached.
For a copy of the request
for proposals, contact
Health Care Coalitions,
Glaxo Wellcome, Inc., 919-483-8584.
Correction:
Hepatitis C Trial
Our last issue announced
a trial of the combination of ribavirin plus alpha interferon for treating
hepatitis C in persons co-infected with HIV. It should have described this
trial as "the first study of [ribavirin plus interferon for] treating hepatitis
C in persons who also have HIV." Due to our error, the words in brackets
were omitted.
Email
Experts; Librarians:
AIDS TREATMENT NEWS Seeks
Expert Advice
By John S. James
We are looking for experts
in two different areas who could volunteer to give us some technical pointers—probably
through a few phone calls or email exchanges.
(1) Email compatibility.
We are quite familiar with email, and know how to send text-only messages
with a short line length so that everybody can receive them correctly.
But most people do not send email that way. At the upcoming 12th World
AIDS Conference in Geneva
(June 28 to July 3) and elsewhere, we will need to provide practical advice
on dealing with issues like: different line lengths, software packages,
file formats, and relevant standards which are in common use around the
world; international alphabets; how to assemble a useful set of file translators
(including non-proprietary ones) to read attached files produced by various
applications and emailed to lists with no regard to how the recipients'
software will read them; under what circumstances are email messages likely
to be lost; and other problems such as spam, censorship by governments,
maintaining confidentiality, and service providers which charge for each
message received.
Also, as a future project,
we want to investigate the possibility of reporting about AIDS with a controlled
vocabulary, for automatic translation into many different languages.
(2) Library outreach. We
need help in developing outreach to get AIDS TREATMENT NEWS into libraries--public,
university, corporate, and other. We have had no organized marketing to
libraries before, and our presence there is poor. We need to know how libraries
place orders, what their financial, seasonal, and other constraints are,
what listings, catalogs, or Web sites we should appear in, how we should
advise library users who want their library to carry AIDS TREATMENT NEWS,
etc.
(3) Database research advice.
For over ten years we have used Dialog Information Services (now The Dialog
Corporation) for specialized searches; it was expensive but we paid only
for what we used. This month Dialog begins charging a minimum bill of $75
per month ($900 per year), so we need to find alternatives. This is a good
time to review and update our entire database search strategy.
The information most important
to us--AIDSLINE/MEDLINE, and Web sites and searches--is already available
without charge. We need strategies for occasional specialized searches--
especially for finding available databases, and working with an affordable
information broker when necessary.
If you can help us in any
of these areas, call or email John S. James, 415-255-6259 or jjames@aidsnews.org.
Prospective
Case Series in Clinical Trial Design-- Proposal, and NTZ Example
By John S. James
Recently the drug NTZ was
rejected by an FDA advisor committee--even though it is widely agreed that
NTZ appears to be safe and may have value for treating cryptosporidiosis
and other intestinal parasites. The rejection happened because the major
clinical trial comparing NTZ to placebo in people with cryptosporidiosis
had to be canceled recently, since very few patients volunteered. The FDA
realized that it would be impossible to run such a trial in the U.S., and
allowed UNIMED Pharmaceuticals, the drug's developer, to present what data
it had. But this information—never intended to be the pivotal data for
approving the drug—did not convince the FDA's analysts or the advisory
committee that NTZ was or was not effective for treating this disease.
We believe this debacle happened
because in modern medical research--and especially in AIDS--only one kind
of clinical trial is likely to be taken seriously: the randomized controlled
trial, in which volunteers are randomly assigned to receive either the
drug being studied, or a standard treatment for the illness (or placebo
if there is no standard treatment, as with cryptosporidiosis). Certainly
this kind of trial has unique advantages, and will continue to be important
in medical research.
But what happens when a controlled
trial is not feasible? Do we throw up our hands and either refuse to study
the drug at all, or try to analyze data which was collected incidentally
during medical care, with little or no thought for research? Today there
is usually no other choice.
To help stimulate thinking
about different kinds of clinical research, we suggest a different kind
of trial, a prospective case series--an organized system of case studies
in which the research team does the best it can for each patient, using
any available treatments (approved or experimental) and absolutely first
class documentation and data collection. The goal would not be statistical
proof, but a document in which the physician-researchers tell what they
have learned about how to treat the illness effectively, and use the data
generated to explain why they have come to believe what they do. The full
data itself could also be published, allowing others to suggest different
interpretations or conclusions.
Design and Size of Study
A team of physicians and
researchers would design the study They would decide such issues
as which patients can enroll, what drugs would be available, what laboratory
and other tests could be provided, and how many volunteers could be accepted.
Unlike controlled trials
which seek statistical answers, the studies we are suggesting do not have
a minimum size which can be calculated mathematically. The number of volunteers
might typically be ten to 40--but it might be as few as one, or it could
depend on the resources available. Patients can be treated and studied
as they arrive, and the researchers will not necessarily have to decide
in advance on the total number of volunteers.
Entry Criteria
In the case of NTZ, one of
the problems with the controlled trial (the one which had to be stopped
because it did no recruit) was the time and difficulty of reaching
a confirmed diagnosis of cryptosporidiosis. Researchers might avoid this
problem by designing clear entry criteria for *suspected* cryptosporidiosis--or
for diarrhea which is suspected to be caused by unidentified protozoa or
bacteria. This approach might be the more practical, since NTZ is probably
safe and is one of the broadest spectrum anti-parasite drugs known-- and
typically in medical practice, diagnosing exactly which pathogens are causing
diarrhea can be difficult or impossible. Instead of waiting for an exact
diagnosis, it may be better to treat certain patients empirically for a
short time, and discontinue the drug if their symptoms do not improve.
(Of course samples would be collected before treatment began, so that changes
in microbiology could be recorded, and correlated with changes in symptoms.)
Treatment
The goal of the physicians
and researchers running the trial would be to provide the best possible
treatment for each volunteer all the time--using almost anything (of course
with the consent of the volunteer, who would have at least one treating
physician independent of the trial).
For example, controlled trials
typically give a fixed dose of one drug for a predetermined time, then
collect statistics on what fraction of patients benefited. In a prospective
case series, the researchers would try to control the disease in every
volunteer; drug doses could be increased or decreased, as appropriate for
that individual. Or the study drug could be combined with other drugs (such
as NTZ with azithromycin, which is also broad spectrum, and may have some
activity against cryptosporidiosis).
With the volunteer's consent,
the researchers might decide to stop treatment early to see if symptoms
return, and start treatment again if they do. This kind of rechallenge
can greatly increase confidence that the drug is (or is not) active in
that particular person.
In some cases the researchers
might decide that it was best for a volunteer not to use the study drug
at all. The person could still stay in the trial and be monitored, could
receive other treatments, and would be included in the analysis.
Data Collection
While the protocol for treatment
would be flexible, the protocol for documentation and data collection would
be exacting. Such information as laboratory tests, concomitant medications,
and rationale for treatment strategies would be recorded at strictly defined
times, and with pre-defined procedures for quality control.
Ethical Supervision
How could such a flexible
study--where there is no rigid treatment protocol, and drugs can be changed
at any time—be effectively controlled by an IRB (Institutional Review Board)?
One approach is to have the
IRB approve a different kind of protocol which is really an "envelope,"
defining all the drugs, tests, and treatment strategies which are likely
to be used in the trial. In exceptional cases where the researchers want
to go outside the envelope, due to new information or to a volunteer's
special circumstances, they would need permission either from the full
IRB, or from a committee which the IRB had designated for that purpose.
Also, every volunteer should
have a treating physician who is unconnected to the research project. This
physician would have access to all the information gathered about the patient,
and could advise the patient to withhold consent for any treatment or procedure.
Advantages
This kind of trial combines
the best available medical care with excellent data collection for research.
Here are some advantages:
The approach focuses directly
on extending the standard of care as a whole--instead of testing just one
drug at a time, due to commercial constraints. It provides a planned, coherent
program of many case studies planned in advance and happening at once.
Recruitment should not be
a problem, since volunteers will be cared for by a team of leading experts
who can use all available information and treatments, who can change treatment
at any time, and who are always trying for the best treatment for each
individual.
Total cost should be small
since relatively few volunteers are needed. And this kind of study can
start quickly without waiting for extensive resources to be assembled,
since no minimum number of subjects is needed, and useful information starts
being generated with the first one. Also, results from the first few volunteers
can provide a database to help justify additional funding or resources
if necessary.
Results can be released as
they are generated. There is no need for secrecy--unlike conventional controlled
trials, where information learned early can threaten later adherence to
the treatment protocol. Here it is intended that treatment will change
as new information becomes available. The goal is always the best treatment
of the individual, using all existing information toward that end.
Even if it fails to produce
definitive or convincing proof of drug efficacy, a prospective case series
can provide highly reliable information about what leading physicians are
doing, what problems they face, and some of the results they are seeing--information
which can help in the design of subsequent controlled trials.
? This approach does not
produce statistical proof like controlled trials do. But it may lead to
comparable or even better confidence in the conclusions drawn. When a controlled
trial reaches the p=.05 statistical significance level which is usually
acceptable, there is (by definition) one chance in 20 that a worthless
drug will pass as effective. In the design we suggest, well-informed physicians
will gain experience with the drug under research conditions—including
seeing how symptoms respond to repeated rechallenge, if appropriate. Although
it is impossible to calculate an exact probability, it seems likely that
after such a trial, a worthless drug may well have less than a one in 20
chance of being considered effective.
Instead of organizing study
design around p-values, statistical analysis can focus on broader issues
of using available information to assist decision making under uncertainty.
Medically, this kind of trial
focuses on exactly the issues that treating physicians face. Treatment
is contemporaneous, meaning that the strategies being tested are the ones
which leading medical experts are using that day. In contrast, conventional
controlled trials test strategies which were current when the trial was
designed, often several years before. And they test treatment by protocol,
which usually differs greatly from medical practice.
We believe these advantages
justify serious attention to this kind of trial--a planned yet very flexible
case series which is designed prospectively and run under research conditions.
Such studies could be used when controlled trials are not feasible, as
with NTZ today. Also, a prospective case series could rapidly provide practical
information useful in designing randomized controlled trials which are
well focused on provable and clinically relevant questions.
AIDS
TREATMENT NEWS
Published twice monthly
Subscription and Editorial
Office:
P.O. Box 411256
San Francisco, CA 94141
800/TREAT-1-2 toll-free
U.S. and Canada
Telephone: 415/255-0588
Fax: 415/255-4659
Email: aidsnews@aidsnews.org
Editor and Publisher: John
S. James
Associate Editor: Tadd T.
Tobias
Reader Services: Tom Fontaine
and Denny Smith
Operations Manager: Danalan
Richard Copeland
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.
ISSN # 1052-4207
Copyright 1998 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.
|