Paul Meier - Statistican who saved millions of lives

http://www.significancemagazine.org/details/webexclusive/1315465/Paul-Meier---Statistican-who-saved-millions-of-lives.html

by ColinWright • 15 years ago

100 8 15 years ago

significancemagazine.org

eumendies• 15 years ago

This is one of those moments for me where you kinda assumed a technique was used in the past, but the truth is it had to be invented. Then when you look at the past with this knowledge, you think, "My god, how barbaric!". Sort of how McCoy (a la Star Trek) acts when he goes back in time.

iwwr• 15 years ago

Not all problems with trials have been ironed out. Only as of 2004, have some medical journals been requiring pre-registration of clinical trials. Previously, drug manufacturers could pretend null results didn't exist.

http://en.wikipedia.org/wiki/Publication_bias

briggsbio2• 15 years ago

First, I think this is a closed view of the issue. Second, I think publication bias has more effect on basic research and translational research (read: early animal pharmacology studies) than drug development.

Conduct of a clinical trial for the purposes of establishing the safety and efficacy of a drug product intended for a specific clinical indication has the goal of registration (NDA, BLA, PMA, 510(k)) of the drug so that the drug can be marketed and sold. Publications are great, and are a component of that, but not the primary goal.

To conduct a clinical study, the company must present all preclinical (FDA calls it nonclinical) pharmacology and toxicology on the drug product to determine whether the product is safe for testing in human trials. This is done via an investigational new drug application (IND, big damn documents that take months to prepare). But I digress...

To conduct a clinical study, the protocol has to be submitted and FDA given time to comment (and they will, often and without much room to argue). That means the patient population, randomization scheme, endpoints, power analysis, etc. are vetted by FDA pretty thoroughly. Next, the same process occurs for the study at local or national (central) institutional review boards (IRBs). They get really nitpicky (especially local university IRBs for numerous reasons). Their primary goal is to ensure the safety of patients, but they won't hesitate to comment on the design of the study in most cases. And (not sure exactly when it became a requirement) sponsors have to register their clinical trial with a national registry (which you can search on clinicaltrials.gov). The results of those studies MUST be submitted to the FDA under the IND, to the IRB, and updated in the registry, or development stops and the IND cancelled.

So unless I misunderstand your comment, the publication practices of journals affects the validity and thoroughness of clinical trial data. This is not the case. Publication bias may alter the available literature, but drugs are NOT registered on publications and effected by "pre-registration." Drugs are developed and brought to market through a seriously controlled and monitored process, not at the whim of medical journals. Now, preclinical data, basic science, "academic studies" not moving a drug toward registration, etc. are affected by publication bias. It is a problem, and pre-registration is a complex issue but beneficial.

One final note: Writing this comment made me think that an alternative form of pre-registration would be really interesting. But not to medical journals, but an open registry for "coming soon research science." Think of a registry of "here's what we want to do" for researchers in basic science, all putting up ideas (ones they are willing to do so openly) for preclinical or clinical studies on the site, indexed by keyword. This would allow researchers to look online and not see what things HAVE been done, but see what things are GOING to be done. This could help researchers identify colleagues (communicate via social features), collaborate on the research, and pool their funding efforts to get multi-institutional grants (usually higher dollar and currently a little less competitive and thus easier to get). Put your research field and interest, and studies you would do "if you had the money" and then the registry would send you recommendations of people to connect with to try and move those research areas forward. If this does not currently exist (which it does not, to my knowledge), it would be amazing to have. It may also be an easier task to implement as a new feature of an existing research social network or community. "Enhancing serendipity in research..." Interesting. Thoughts?

sigil• 15 years ago

Hopefully obvious, but some of this stuff also applies to A/B testing.

Yet in the 1950s the usual technique was to give a new treatment to the patients whom it was thought would most benefit from it. It frequently happened that those were the patients whose chances of recovery were the best in any case, under the existing treatments as well as the new one. The result was all too often that new treatments were thought to be better than old ones but in fact were not.

gwern• 15 years ago

> ‘When I said “randomize” in breast cancer trials I was looked at with amazement by my clinical colleagues’ said Meier in an interview in 2004. ‘ “Randomize? We know this treatment is better than that one” they said. I said “Not really…” ’

Paul Meier - Statistican who saved millions of lives

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