
Flaws in the clinical trials for Gardasil made it harder to assess safety - ehudla
https://slate.com/health-and-science/2017/12/flaws-in-the-clinical-trials-for-gardasil-made-it-harder-to-properly-assess-safety.html
======
defined
I wonder if any efforts have been made to conduct a deep review of clinical
trials to see if there are patterns of protocol design that are likely to lead
to underreporting of adverse effects.

As (unfortunately) a user of a number of prescription medications, I have
encountered adverse effects that were considered uncommon, yet heard about
similar issues from fellow users. Of course, this is anecdata, so one can draw
no conclusions, but I have a nagging suspicion that enough digging by people
who truly understand statistics will find flaws, perhaps major ones.

Not likely to happen, though.

~~~
rjdagost
There are a number of reasons why problems can slip through clinical trials,
even with proper clinical trials design.

Some side effects are extremely rare, so rare that even with “large” clinical
trials groups the problems don’t occur. Or they might occur, but at rates no
greater than what the placebo group experiences. Some side effects only show
up with repeated long-term use of a drug. That’s why there exists “post
approval monitoring” to watch for these problems. Some side effects only show
up when a drug is taken concomitantly with other drugs. Some side effects only
show up when users have certain diets. Some side effects (and some efficacies)
only show up for certain ethnicities and sub-populations. Some side effects
only show up when patients take much larger doses than were tested in clinical
trials.

Larger statistical samples would help to reduce these problems, but it’s often
not as easy as you might think to recruit large numbers of people for your
study. First, it is quite expensive to put a large test group together. Some
diseases / conditions are quite rare, so it can be difficult to even find
enough people with the condition. As the test runs through, some fraction of
the participants will drop out for one reason or another. Some people will
just stop taking the medication for one reason or another. How you treat these
“dropouts” is not a simple question and can have a huge impact on your
clinical trials conclusions. Some test measures are highly subjective and
experts will disagree on how efficacious / dangerous a drug is when presented
with the same exact data.

The bottom line is that drug approval is extremely complicated. Better test
design and monitoring helps but it will not catch all problems. Regulators
have to balance safety with benefits in the face of uncertainty.

------
YeGoblynQueenne
>> Not owning up to that uncertainty, when it is legitimate, likely will only
slow scientific progress. In the controversial realm of vaccines, it will also
create fodder for conspiracy theorists spreading overblown or unfounded fears
among an already distrustful public.

Just when did "the realm of vaccines" become "controversial"?

Also, one thing I couldn't figure out from the article is whether Lyng and the
other women who suffered after taking part in the vaccine trials actually
received the vaccine, rather than a placebo. Is that information even
recorded?

------
pdfernhout
On conflict of interest during Gardasil's testing in India:
[http://www.corpwatch.org/article.php?id=14401](http://www.corpwatch.org/article.php?id=14401)
"JayaJan Pharmaceutical Research in India was one of the companies with which
Merck had a contract to test Gardasil. Like most of the industry, Merck
increasingly outsources its clinical trials to Contract Research Organizations
(CROs) in areas of the world where trial subjects are plentiful, operating
costs are low, and regulations lax. .. Critics point out that CROs can come
with built-in problems. Conflicts of interest can arise when CROs are paid
royalties only after a drug is approved rather than being paid a set fee that
is independent of how safe or effective the drug turns out to be. Problems can
also arise because CROs know that favorable findings mean that research into a
test drug will continue, and they may also believe that results that please
the hiring corporation can lead to future contracts. "[C]ompanies know that
the farther the compound moves through the research cycle, the more money they
can raise," Nature reported."

Also on India and a Gardasil Supreme Court case questioning safety:
[http://sanevax.org/india-supreme-court-hpv-vaccine-
controver...](http://sanevax.org/india-supreme-court-hpv-vaccine-controversy-
continues/)

And from Mercola questioning its effectiveness:
[https://articles.mercola.com/sites/articles/archive/2010/12/...](https://articles.mercola.com/sites/articles/archive/2010/12/29/why-
india-has-stopped-giving-hpv-vaccines.aspx)

In general from Marcia Angell:
[http://www.nybooks.com/articles/archives/2009/jan/15/drug-
co...](http://www.nybooks.com/articles/archives/2009/jan/15/drug-companies-
doctorsa-story-of-corruption/) "The problems I've discussed are not limited to
psychiatry, although they reach their most florid form there. Similar
conflicts of interest and biases exist in virtually every field of medicine,
particularly those that rely heavily on drugs or devices. It is simply no
longer possible to believe much of the clinical research that is published, or
to rely on the judgment of trusted physicians or authoritative medical
guidelines. I take no pleasure in this conclusion, which I reached slowly and
reluctantly over my two decades as an editor of The New England Journal of
Medicine."

~~~
djsumdog
I feel like a lot of people on HN don't want to promote "vaccine denialism,"
but the reality is that you cannot put all vaccines, nor can you put all
drugs, in the same category.

Many vaccines have done a lot of good. Many of the people who question some of
the more recent vaccines are not against the standard MMR.

I don't think it's wrong to question newer pharmaceutical products, including
drugs, devices and vaccines. Remember Vioxx?

Clinical trials have a lot of safeguards, but we've seen how business
interests can side step these. A lot of money goes into studying new
compounds. If during the animal trials, if a single monkey dies, your entire
compound is often scraped and has to go back quite a but. At the human side of
testing, potential issues can mean a lot of money being scrapped.

It's a bigger problem with how we develop drugs, and it's also a bigger
problem with how we see science, especially the mixture of science and
funding. James Corbet has a great video about the "Weaponization of Science"
which is worth considering:
[https://www.youtube.com/watch?v=yecefLsE44U](https://www.youtube.com/watch?v=yecefLsE44U)

