September 17, 2008

The Process of Bringing New Drugs To Market

An interview with Alan J. Milbauer, a retired vice president from AstraZeneca and partly responsible for Seroquel, about what goes into the process we're all angry about.

How were decisions made about which drug should be developed?

Mr. Milbauer: We were a company dedicated to finding breakthrough drugs, but we could not afford to put all of our eggs in that basket. So, we needed to consider many factors beyond the breakthrough potential when we chose a drug for further clinical development.

...One example is the drug Zoladex (goserelin) a one- or three-month injectable depot used to treat prostate cancer. This injectable LH/RH analogue suppresses testosterone and might obviate the need for surgery in some cases. Initially, we thought our market would be the oncologists but quickly realized that our real targeted physician group was urologists. Well, urologists are surgeons and we were introducing a treatment that was an alternative to surgery! Although we believed we had a treatment that was good for patients, we had to convince the urologists to store an injectable drug, get reimbursement from third-party insurers, including the Federal government, and forego surgery.

Observe that in this example, the actual efficacy of Zoladex worked against it: the doctors who would use it were, in fact, least likely to want to use it.  Do you think they were bad doctors, corrupt and only out to make money?  No.  their paradigm was cut, cut, cut, even though easy efficacy in a medication was staring them right in the face, they couldn't see it, really see it.  Like trying to convince a vegeterian to try a burger.  "No way can this be as good as what's been working for me.  I'll stick to what's worked for me so far."

But that's the problem, exactly: medicine is practiced by what works for the doctor, not the patient.

How do you change a mini-paradigm like this, when doctors are resistant to data, journal articles, logic?  What has to be done is this:

We identified key opinion leaders to work with our drug and ultimately we changed some of their perceptions and practices.
Medicine is not science, it is politics.  It is no different than a lobbyist convincing a senator to vote for ANWAR drilling vs wind power subsidies, or both.

The most poignant part of the interview was at the end:

Looking back on your years in the pharmaceutical industry, what was the most challenging part of your job?

Mr. Milbauer: Sometimes I had to convince senior management to drop a drug from development because, in our commercial judgment, the product was unlikely to be successful. The reasons could have been competitive positioning or the amount of commercial resources required, pricing issues, dosing or safety issues, or patient acceptance...but those reasons frequently did not matter to the scientists who had been advocating for the drug. I found myself having to persuade people who had spent many years developing "their" compound that it was not in the company's best interest to pursue the drug, and often these people had difficulty accepting the corporate perspective. But, it was a business after all.

Before you misread this as "money trumps science" go back and re-read the rest of this post.  These scientists are not advocating for the cure for AIDS.  It could be another Zoloft, or another Celebrex, or another Viagra.  What matters to the scientists was that it was their drug, their discovery, their child, sometimes the scientists were vehemently advocating for a drug that was neither important nor profitable.

Part of the problem is that scientists are incentivized on gaining FDA approval, and not future sales OR usefulness.

And that's why the model must change.