[Cz-biology] [Cz-health-sci] Merck proposal is NOT A GOOD IDEA

[Oliver Hauss]

Badgett, Robert G schrieb:
>
> Thanks for the opportunity to discuss this. I would not touch this
> offer either.
>
> Aside from the Viox incident in which Merck is alleged to have
> withheld negative data from the NEJM (See Failing the Public Health —
> Rofecoxib, Merck, and the FDA - http://pmid.us/15470193) (See
> Expression of Concern - http://pmid.us/16339408) and publishing a
> deceptive meta-analysis (http://pmid.us/14564311), there are numerous
> studies of the hazards of conflicts of interest.
>
Bob, do you consider bringing up "alleged" misconduct as a good
demonstration of your own impartiality?  The conduct of NEJM itself in
this affair was far from stellar. The hazards of conflicts of interest
exist totally independently of whether someone works for a company or not.

> In the CZ evidence-based medicine article, I started a summary of
> empiric studies on the problems with conflict of interest in
> medicine(http://en.citizendium.org/wiki/Evidence-based_medicine#Conflict_of_interest).
>
...sorry, but we're neither talking about clinical trials of drugs nor
about "the industry" in general. Statistical evidence says only
something about likelihood in individual cases, but is no evidence for
the individual case, and we're talking about one individual company
here. To use these studies in the discussion here is an abuse of statistics.

> Perhaps a worse problem is that our relating with a conflicted entity
> may induce /bad behavior on our part/. See the start of a summary of
> this at
> http://en.citizendium.org/wiki/Medical_ethics#Effect_on_the_conduct_of_research_and_publishing.
> Most disturbing is the Stelfox NEJM study (http://pmid.us/9420342)
> listed at the preceding link.
>
With the first line, you basically destroy your own argumentation. Your
suggestion here that such bias would only be introduced by our
association with Merck is intenable. It very likely already exists with
numerous authors -the only logical consequence would be to fold our
things and go if this risk is totally unacceptable.


> Focusing now just on the quality of the Merck manual, there must be
> something good going on as it is in its 18th edition. However, in
> 1992, Antman showed the inaccuracies of traditionally edited textbooks
> that rely on the unaided expert (http://pmid.us/1535110). Since then,
> medical texts have improved their methods to include things such as
> peer review, disclosing authors' conflicts of interest, attributing
> source evidence, frequent updating with literature searches supplied
> to authors from a central editorial office. The Merck Manuel does none
> of these and does not have an adequately transparent process.
>
Sorry, but from personal experience, I seriously doubt this. Our own
article on iron deficiency anemia, until I went over it the other day,
had simply taken over from Wikipedia markers for iron deficiency that
are plain and simply useless in the event of chronic kidney disease (and
some even in general) and was completely lacking markers that are openly
advocated in the respective guidelines (which themselves are more
instruments of policy and politics than evicence-based medicine). You
yourself simply included references in the article, without a hint of
verifying whether the references are outdated or not. Despite the fact
that you noted that the article still has disputable statements, you
chose to give it more credibility by simply tacking some sources onto
it. You used a source from 1990 -more than 15 years old!- to support a
claim which YOU introduced that ferritin was the most sensitive test for
iron deficiency anemia (
http://en.citizendium.org/wiki?title=Iron_deficiency_anemia&diff=100190016&oldid=100126447
) . I should consider this an insult, since you imply the diagnostics
industry has not done any R&D in hematology in 20 years. But frankly,
given the development of life sciences over the last 20 years, anyone
should pause and ask himself what he is doing here before citing papers
this old. While ferritin is still included in the KDOQI guidelines, it
is used there only and exclusively in combination with TSAT or
reticulocyte hemoglobin content. The same holds true for other
guidelines. And in fact, some studies have shown that contrary to the
claims you introduced, the sensitivity of ferritin can be abysmal:
http://cjasn.asnjournals.org/cgi/content/full/1/Supplement_1/S4/T1

If you believe it is better to do so, I will revert my changes since my
employer sells instruments with which you can measure some, but not all
of the parameters at issue. However, the paper I cited was actually done
on a competition instrument. So it's your choice: Do you want to spread
outdated information that seriously threatens the health of people for
the sake of a fig leaf against bias or are you interested in the
information being accurate? Do you want Citizendium to make false claims
because YOU introduced them and not someone from the diagnostics
industry who, for the very reason that he works in the field, is
familiar with pertinent literature?

> So, there is theoretical risk that the Merck Manual is compromised and
> maybe biased. Let's look:
>
> 1. It is interesting that if you search rofexocib in the Merck manual
> you get 0 hits.
>
Why is it interesting? Rofexocib has been withdrawn. It is not an
available drug in this context and as such, there is no reason to
mention it. If you look into the article on pain
(http://www.merck.com/mmpe/sec16/ch209/ch209a.html) , it goes into COX-2
inhibitors at length: "NSAIDs include nonselective COX (COX-1 and COX-2)
inhibitors and selective COX-2 inhibitors (coxibs); all are effective
analgesics. Aspirin is the least expensive but has prolonged
antiplatelet effects. Coxibs have lowest risk of ulcer formation and GI
upset. However, when a coxib is used with low-dose aspirin, it may have
no GI benefit over other NSAIDs. Recent studies suggest that inhibition
of COX-2, which occurs with both nonselective COX inhibitors and coxibs,
is associated with a prothrombotic effect that can increase risk of MI,
stroke, and claudication. This effect appears to be drug-related, as
well as dose- and duration-related. Although there is some evidence that
the risk is very low with some of the nonselective COX inhibitors (eg,
ibuprofen, naproxen) and coxibs (celecoxib), it is prudent to consider
the potential for prothrombotic effects as a risk of all NSAID therapy."

> 2. Another example: if you search Merck for "cox", you find this
> statement in the osteoarthritis chapter
> (http://www.merck.com/mmpe/sec04/ch034/ch034e.html), "NSAIDs,
> including cyclooxygenase-2 (COX-2) inhibitors or coxibs, may be
> considered if patients have refractory pain or signs of inflammation
> (eg, redness, warmth). NSAIDs may be used simultaneously with other
> analgesics (eg, tramadol, opioids) to provide better relief of
> symptoms." Does any MD on this list agree with this clinical
> recommendation by Merck? The Merck Manual omitted that the Cox-2 drugs
> might increase myocardial infarctions. It seems the Stelfox bias has
> occurred.
>
It seems there's bias here on your part. First of all, you tear out one
paragraph from the region of drug therapy and suppress the information
that it is much more elaborate. Second, you suppress that the article on
pain lists those risks. Lastly, you suppress that the information is
included in documentation on the specific drug including in the
information provided by a drug's manufacturer which the Merck Manual
explicitly advises to consult before prescribing or administering a drug.

Lastly, if you actually look at the Osteoarthritis chapter of the HOME
EDITION
(http://www.merck.com/mmhe/sec05/ch066/ch066a.html#sec05-ch066-ch066a-328
),  you find "However, one of the coxibs, rofecoxib (withdrawn from the
market), appears to increase the risk of heart attack and stroke after
long term use. The risk with other coxibs is being studied. Because one
recent study has shown a 2.5 fold increase in cardiovascular problems
with another coxib, celecoxib current FDA recommendations are to limit
use of any coxib to people at high risk of gastrointestinal bleeding,
who have a history of intolerance to other NSAIDs, or who are not doing
well on other NSAIDs. Caution should be taken with use of coxibs for
long periods or by people with risk factors for heart attack and
stroke." -shattering both your complaint that rofexocib isn't mentioned
and the failure to point at the risks of Cox-2 inhibitor.

> So even if we think the Manuel operates with editorial independence
> from the Merck company, we have to deal with the quality of the Merck
> Manual.
>
> In summary, I believe the Merck Manual's methods are outdated and
> there is evidence of inconsistent quality of content. Given time, we
> can write better content. When this happens, it might be hard to
> jettison the Merck links.
>
We have to deal with the quality of each and everyone's work, and not
just with that of the Merck Manual's editorial team. And the first and
foremost person with whose quality of work one should be concerned with
is oneself. The first and foremost hallmark of sound scientific conduct
is self-skepticism. Before accusing others of outdated methods and
inconsistent quality, how about assessing your own work critically first?

If we say that we shouldn't use the Merck information because it doesn't
cite peer-reviewed literature, I can certainly support that. When
talking about bias, however, everyone should first and foremost think
about his own. Suggesting people "flip a switch" when they join the
industry is just as ridiculous as the assumtion that people not
officially on the payroll of a company don't have any bias.

One other thing that I'd like to throw into the discussion is whether
the home edition of the Merck Manual isn't a better place to link to,
since it is written for the general reader and as such much more
accessible for the average reader of CZ. But that's a whole different
issue. In the meantime, I thank Gareth Lang for his voice of reason.
Sorry if some of this is sharply-worded, but trying to sell one's own
biases as adhering to good scientific conduct is using a pretty big
excavator for the grave of CZ's credibility.

Oliver Hauss