[Ip-health] Combined Pills
amir_attaran@harvard.edu
amir_attaran@harvard.edu
Sat, 6 Oct 2001 13:36:34 -0400
Dear Mr. Jefferys,
You write that:
"Trizivir...was approved in the US without submission of any trial data
from the combined pill whatsoever."
That is false. The clinical trials I were speaking of, in case you were
unable to gather from the context, were bioequivalence trials. It was the
lack of bioequivalence trials that I was concerned about, and also which
Mr. Zackie Achmat of TAC was concerned about. If you check my message of
earlier, the word "bioequivalence" cropped up several times, so I would
have thought that was clear.
If you doubt that bioequivalence trials were performed on Trizivir, the URL
you send me below reads:
"CLINICAL PHARMACOLOGY:
Pharmacokinetics in Adults:
TRIZIVIR: In a single-dose, 3-way crossover bioavailability study of 1
TRIZIVIR tablet versus 1 ZIAGEN tablet (300 mg), 1 EPIVIR tablet (150
mg), plus 1 RETROVIR tablet (300 mg) administered simultaneously in
healthy subjects (n = 24), there was no difference in the extent of
absorption, as measured by the area under the plasma concentration-time
curve (AUC) and maximal peak concentration (Cmax), of all 3 components.
One TRIZIVIR tablet was bioequivalent to 1 ZIAGEN tablet (300 mg), 1
EPIVIR tablet (150 mg), plus 1 RETROVIR tablet (300 mg) following
single-dose administration to fasting healthy subjects (n = 24)."
If you are not a biomedical scientist (I apologise if you are), you might
not notice that those are bioequivalence data, and that is fair enough.
But as someone who read the document you rely on, you should have noticed
your very selective use of quotes, which seems crafted to mislead. I mean
specifically that when you quote the Trizivir URL as reading:
"There have been no clinical trials conducted with Trizivir."
The rest of that sentence, which you cut out, continues to deal with
bioequivalence:
"There have been no clinical trials conducted with TRIZIVIR (see
CLINICAL PHARMACOLOGY for information about bioequivalence of
TRIZIVIR)."
Omitting those last few words, as you did, leaves the impression that no
bioequivalence testing was done on Trizivir, which is certainly not the
case.
Therefore my propositions remain true as before:
1. The generic antiretrovirals have not been through bioequivalence
testing, while the brand name ones (including Trizivir) have.
2. There is a serious ethical question in activists urging that Africans
use generic antiretrovirals which have not undergone bioequivalence
testing, when we would NEVER use these in the United States or Europe.
3. That is not only my view, lest I be though of as a shill for
industry, but also the view of Mr. Achmat and Treatment Action Campaign
.
4. EVERYONE agrees that bioequvalence studies need to be done urgently.
But until that's done successfully, it seems to me that activists need a
self-imposed moratorium on promoting generic antiretrovirals to poor
countries, for obvious ethical reasons. If it were more widely known
that activists were promoting products that short-circuit this important
testing for safety and efficacy, it could in the long-run trigger a
backlash that makes poor countries LESS willing to use generics,
INCLUDING the ones which are bioequivalence tested, and that would be
counter-productive to say the least. This backlash is already
happening, and it is notable that most of the countries in Africa which
have bought antiretrovirals have bought them from brand name companies,
not generics, in part because of safety concerns.
Therefore, it would be my advice, as a more ethical and more intelligent
long-run strategy, for activists to put a moratorium on promoting the
generic antiretrovirals for now, and raise the funds to perform the needed
bioavailability studies with all possible speed.
Sincerely,
Dr. Amir Attaran
rjefferys@hotmail.com
Sent by: To: ip-health@venice.essential.org
ip-health-admin@venice.ess cc:
ential.org Subject: Re: [Ip-health] Combined Pills
10/06/2001 12:25 PM
amir_attaran@harvard.edu wrote:
>There is no study of the safety and efficacy
>of those single-pill fomulations in the biomedical literature, and they
are
>therefore unproven.
This is true of GlaxoSmithKline's Trizivir, which was approved in the US
without submission of any trial data from the combined pill whatsoever. The
label plainly says: "There have been no clinical trials conducted with
Trizivir."
http://www.glaxowellcome.com/pi/trizivir.pdf
>This raises an important ethical consideration: ought one to advocate for
>products to be used in Africa, if those products have not undergone the
>same safety and efficacy trials as the products used by AIDS patients in
>North America or Europe?
Trizivir was approved based on the three included drugs being studied
together, as indeed d4T(or AZT)/3TC/nevirapine have been studied in
combination. You seem to want to raise an ethical consideration, even if
none exists. The bioequivalence issue for generics can surely be rationally
addressed (ACT-UP Paris have recently taken a look at some of CIPLA's
products, for example).
>The third single-pill formulation you refer to is marketed by
>GlaxoSmithKline as Trizivir, and the company discounts it heavily for
>Africa. It has been through clinical trials, and as such, it is a fully
>acceptable HAART regimen without the above ethical issues.
Not true.
>But having said this, please address this lacuna in your argument: You
>cite the example of three HAART regimens which are patented, but you
>assiduously avoid mentioning whether there exist several other HAART
>regimens which are minimally patented in Africa. Are there? I know the
>(embargoed) answer, but perhaps you can use the PhRMA data in your
>possession, and write back to this list with a fuller analysis of that
>question.
So, you're suggesting that attempts to encourage purchase and distribution
of HAART in the global south should focus on regimens that might not be
patented? This is ethical? I think this only reinforces the point that,
depending on their location, a person's standard of HIV care is profoundly,
unethically and immorally governed by current trade law and it's
consequences for accessibility and affordability of HAART drugs.
Richard Jefferys
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