ALLIANCE FOR HUMAN RESEARCH PROTECTION
Promoting Openness, Full Disclosure, and Accountability
http://www.ahrp.org and http://ahrp.blogspot.com

FYI
Merril Goozner head of Integrity in Science reports (below) that "FDA Scraps
Helsinki Declaration on Protecting Human Subjects."

In so doing, the FDA has taken a quantum leap down the slippery slope toward
uncivilized medical experimentation.
The agency is lending the US government seal of approval to unethical
medical experiments (primarily commercial drug and medical device tests).

A recent example of an FDA approved, lethal experiment is a trial testing
Northfield's artificial blood product, PolyHeme--even as the company and the
FDA had evidence showing that patients' exposed to the product were at
higher risk of death than those who were given saline.

In one Illinois town where the product was tested, 83% of the population is
black. "If you look at the absolute number of deaths, it kills more patients
than saline does."

Such experimentation harks back to the Nazi regime's version of
medicine--not civilized medicine that America is supposed to represent.

See:
http://ahrp.blogspot.com/2008/04/in-december-2006-we-stated-american.html

1. Charles Natanson; Steven J. Kern; Peter Lurie; Steven M. Banks; Sidney
M. Wolfe Cell-Free Hemoglobin-Based Blood Substitutes and Risk of Myocardial
Infarction and Death: A Meta-analysis JAMA, Apr 2008;
doi:10.1001/jama.299.19.

2. Dean A. Fergusson; Lauralyn McIntyre The Future of Clinical Trials
Evaluating Blood Substitutes. Editorial. JAMA, Apr 2008;
doi:10.1001/jama.299.19.


Contact: Vera Hassner Sharav
veracare@...
212-595-8974


http://www.gooznews.com/archives/001052.html
GoozNews
May 08, 2008
FDA Scraps Helsinki Declaration on Protecting Human Subjects

In the mid-1990s, the National Institutes of Health ran a clinical trial in
Africa testing whether a new antiretroviral drug to combat AIDS worked to
prevent mother-child transmission. The trial created an ethical uproar
because the control group received a placebo instead of an older anti-AIDS
drug called AZT, which had already been proven successful in reducing the
number of babies who contracted HIV from their mothers.

To critics, failure to provide a proven therapy to participants in this and
similar trials was a basic violation of standards outlined in the Helsinki
Declaration on protecting human subjects in research, originally adopted by
the World Medical Association in 1964. But to the U.S. Food and Drug
Administration and the drug industry, to which it had grown increasingly
close over the course of the 1990s, it contradicted its longstanding policy
of only requiring trials showing that a new drug was "better than nothing,"
i.e., better than placebo, to win regulatory approval. If the drug industry
were to closely adhere to the Helsinki Declaration, it would always have to
run comparison trials if an effective drug were already available.

Rather than accede to international norms, the FDA and the U.S. government
in the succeeding years lobbied hard to get the WMA to amend its rules. And
it has, several times. For instance, it now allows use of placebo-controlled
trials for less serious illnesses. But the basic guidelines protecting human
trial subjects' access to best available therapies remained intact.

Why is any of this relevant today? Last week, the FDA formally declared that
it will no longer require that clinical trials submitted to the agency to
get regulatory approval for a new drug adhere to the Helsinki Declaration.
The new rule, which goes into effect next October, was supported by the drug
industry but opposed by numerous public interest, patient advocacy, and
consumer groups. The new rule requires only that trials conducted abroad by
drug manufacturers follow good clinical practices (GCP) and include a review
and approval by an independent ethics committee. There's nothing in GCP
guidelines that requires patients in the control arm of a trial get access
to already proven therapies. They only need receive the standard of care in
that country.

What will this mean for the concept of "informed consent" in a poor country?
Imagine for a moment that you live on $2 a day in, say, Zimbabwe, and have
high blood pressure. Since the disease isn't life-threatening, you skip
buying the available anti-hypertensives being sold in the village pharmacy
because you can't afford them and none are on the national formulary. Hence,
there is no local standard of care.

Now say you learn while visiting the village clinic that an international
pharmaceutical company is recruiting patients for a clinical trial testing a
new anti-hypertensive drug. If you join the trial, you may only get the
placebo. But there's a 50-50 chance you will get the new drug, which hasn't
been proven yet, but might work.

Are there risks associated with taking this new drug? Well, so far, none
that the doctors think are serious enough to cancel the trial. But it says
right on the form that something may turn up in the clinical trial in which
you are being asked to participate. You sign up. After all, a 50-50 chance
of getting a drug that has a good chance of working (the drug industry
wouldn't be here testing it if it didn't, right?) is better than no drug at
all. And how much risk could there be, anyway?

Is that really non-coerced, informed consent?

It's getting tougher and tougher to recruit patients in the U.S. to
participate in clinical trials. It's also getting a lot more expensive for
drug companies to run them here. The result is that 35 percent of all trials
submitted to the FDA in new drug applications now take place abroad. This
new rule will only make that number grow.

Moreover, many of those trials conducted abroad (or about 15 percent of all
trials) aren't even be registered with the FDA. Unlike trials conducted in
the U.S., companies do not have to submit an investigative new drug
application (IND) to the FDA before beginning research in foreign countries.
The FDA estimates about 575 of the foreign trials submitted to the agency
each year as part of new drug applications do not go through the IND
process. In other words, the FDA has no record that they even exist.

The FDA is required by law to monitor clinical trials conducted under INDs
to protect their human subjects. But an Inspector General's report released
last September found that the FDA had no registry of trials (which was
rectified by passage of the FDA reform law last October); no registry of the
Institutional Review Boards that were supposed to be monitoring trials
conducted under its auspices; and independently monitored fewer than one
percent of the trials it knew about.

And now it has passed a rule that increases the likelihood that more trials
will go abroad and that more of them will not even be registered with the
FDA, which makes them all but impossible to monitor.

In the final rule published in the Federal Register, the FDA rejected the
notion that adopting the self-regulating GCP standard and eliminating
references to the Helsinki Declaration "will hurt subjects in developing
countries or result in less protection for subjects in foreign studies." The
agency noted that GCP requires trial sponsors closely monitor trial behavior
and report adverse events. If I were a headline writer at the New York Daily
News, the headline on that story would have been: FDA to Global Poor: Drop
Dead.

What I can't understand is why no one in the U.S. press, including in the
medical literature, paid attention to this story in the past year as this
change was underway. Has the U.S. become entirely callous about the impact
its ill-conceived policies are having on the rest of the world? Or am I
off-base and this stuff really doesn't matter.
Posted by gooznews at May 8, 2008 08:38 AM

Comments

GCP requires that the study provide the control arm with the "standard of
care." GCPs do NOT say to run it against a placebo. The sticky part is in
those cases where the test is being conducted where the standard of care is
different (less) than it is in the US.
The FDA explains this change in the text of the CFR:
First,we noted that standards for protecting human subjects have evolved
considerably over the past decade, as evidenced by revisions of the
Declaration by the WMA’s General Assembly and the issuance of several
documents by the International Conference on Harmonisation of Technical
Requirements for Registration of Pharmaceuticals for Human Use (ICH). We
noted that the ICH document‘‘E6 Good Clinical Practice: Consolidated
Guideline’’ (ICH E6),which we adopted for use as guidance for industry in
1997 (62 FR 25692, May
9, 1997), includes a definition of GCP that shares many important ethical
principles with the 1989 Declaration.1 However, we stated that the concept
of GCP in ICH E6 provides more detail and enumeration of specific
responsibilities of various parties, including monitoring of the trial and
reporting adverse events.
Although we did not specifically incorporate ICH E6 into the proposed
revision of § 312.120, we stated that the standard of GCP that we proposed
for § 312.120 was consistent with that in ICH E6 and was sufficiently
flexible to accommodate differences in how countries regulate the conduct of
clinical research and obtain informed consent, while helping to ensure
adequate and comparable human subject protection.
Posted by: Kelly at May 8, 2008 03:52 PM

I read that to mean that if a country has a standard of care that is less
than the best available treatment anywhere in the world, a company can offer
that in a clinical trial and get away with it. Is it ethical for physicians
representing a foreign drug company to offer that less-than-optimal local
standard in a controlled clinical trial, knowing the other is out there?
That's the nub of the ethical dilemma, which isn't addressed by careful
monitoring or adverse event reporting.
Posted by: Merrill at May 8, 2008 04:53 PM

FDA Week, of which I'm the editor, has run two articles on this regulation
since January. I mention this neither to market the publication nor to pat
myself on the back. Rather, I'd like to point out that a few major
newspapers subscribe to us so they should know about it.
Posted by: John Wilkerson at May 8, 2008 06:06 PM

I should have noted that the trade press has covered this change. It was the
mainstream media's lack of interest that concerned me. Many people in the
developing world distrust the U.S., and issues like this, should they come
to light under scandalous circumstances, would only fan those flames for no
other purpose than to make it easier for manufacturers to run clinical
trials in poor countries.
Posted by: Merrill at May 9, 2008 06:16 AM

We need to distinguish b/w what is ethical and what is profitable. Secondly,
who are the real stakeholders and their resources. It is like comparing
apples with oranges, but in a different context. The ethical component is
liable to be overshadowed and shelved, esp. in the so-called 'emerging
economies'. Since, inviting dollars or Euros is the prerogative, esp. since
literacy, human rights, and civic responsibility are still not at par with
the so-called first world. Public interest, patient advocacy, and consumer
groups is a far cry away. It is economics and interests that rule in the
emerging economies. As such all are at one level or another violating
patient's rights. Informed consent may be relevant in the western nations,
but I doubt new recruits pay much attention or even understand what they are
getting into, except for some distant hope that they will get some form of
occidental treatment. Regulatory bodies and PI's are basically blind
signatory entities who offer lip service if at all.
The situation as far as ethics is concerned at this basic fundamental level
appears gloomy, and FDA's rulings don't help either. It is all about vested
interests, not necessarily better treatment options, as such the smashing
term for next best drug in the pipeline, "blockbuster drugs".
Local regulatory bodies in the emerging economies themselves must be
resilient, have strong regulatory bodies capable of resisting pressures and
not be subservient to vested interests.
What hope is there for the Tanzanian? He's is just trying to survive as long
as life permits him.
Posted by: Faisal Roohi at May 10, 2008 04:59 AM

So...now the FDA and Pharma are legitimizing, abroad, the sort of medical
research once done with people of color in this country...the Tuskeegee
model.
Posted by: byard pidgeon at May 10, 2008 03:53 PM

Byard--

Evidently you have that right. I imagine FDA/Pharma response would be, "Why
let a 'good model' go to waste . . . just outsource it, and keep the prying
eyes (or perhaps, not so prying--rather disinterested) out of the mix. I
read a quote the other day that accurately reflects MY opinion of our
healthcare/regulatory system, (with direction from BigPharma): Attributed to
comedienne Lily Tomlin--"No matter how cynical I get, I just can't keep up."
Posted by: Melody at May 10, 2008 04:52 PM

Yes, mainstream media does not believe the general public cares, but WE DO.
I also suspect reporters are denied the chance to cover such a story.
Another reason our news must stop being "owned" by fewer and fewer
individuals Vs conglomerates. A free press is the foundation of our
free-thinking USA. Doctors and lawyers and the wealthy in this country read
their OWN literature and discuss it among themselves. Average Joe is just
too dumb. And guess who gets scr****? Right. Middle class, minorities, the
elderly and poor. Is this what our country is meant to be?
Posted by: Diane J Standiford at May 11, 2008 09:01 AM




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