Committed to the Quest

December 1, 2001
Steven W. Mayo

Steven W. Mayo, PD, CCRA, is the founder and CEO of Emissary, an international contract research organization. He can be reached at smayo@SendEmissary.com.

Pharmaceutical Executive

Pharmaceutical Executive, Pharmaceutical Executive-12-01-2001, Volume 0, Issue 0

It all started because of a commitment I made when I was too young to understand what I was getting myself into. My mother had headaches. Not "throbbing in the temples" headaches, but gut-wrenching, totally incapacitating, "rip the carpet out with your bare hands" headaches. Migraine, cluster headache, trigeminal neuralgia-whatever the flavor, they were really bad. She saw practically every specialist in the country. They gave her ergotamine injections until her fingers turned blue, narcotics powerful enough to stop a charging elephant, and dozens of other medications, many of which were experimental at the time. Nothing worked.

It all started because of a commitment I made when I was too young to understand what I was getting myself into. My mother had headaches. Not "throbbing in the temples" headaches, but gut-wrenching, totally incapacitating, "rip the carpet out with your bare hands" headaches. Migraine, cluster headache, trigeminal neuralgia-whatever the flavor, they were really bad. She saw practically every specialist in the country. They gave her ergotamine injections until her fingers turned blue, narcotics powerful enough to stop a charging elephant, and dozens of other medications, many of which were experimental at the time. Nothing worked.

So I decided to help find an answer. It was a promise I made to myself-an altruistic, if somewhat self-serving, pledge. I didn't just want to help my mother. I wanted to ensure that no one, including frightened young children like myself, would ever again have to endure or witness such agony.

Medical school was out of the question. I was still a kid, and the thought of staying in school until I was 30 was more than I could bear. It didn't help that I was so squeamish that I came down with an exotic disease almost every time my biology class dissected a frog.

So I went to pharmacy school instead. After graduating, I began working for a pharmaceutical company in analgesics. My first assignment was developing "Harter graphs"-affectionately named for the FDA reviewer who requested that we compile them-comparing pre- and post-treatment changes in laboratory values for a pediatric analgesic's new drug application. It was shortly after that tedious challenge that I learned several important lessons about pharmaceutical research and development:

It's a competitive business. My company's baby, the product of adoring labor and nurturing love, reached the market. But we never got the chance to sell it under our label. Lacking a large sales force, the company signed a co-branding agreement with a pharma giant. They had much better lawyers.

So we embarked on an even nobler quest. The company's crack team of chemists found that dogs, when given an experimental antibiotic, had an unexpected reaction: Their blood pressure dropped. Eureka! A new treatment for hypertension.

Unfortunately, after a year or two of intensive testing-this time on human volunteers-and after investing a measly $10 or $20 million, we discovered that it also increased heart rate. Although the increase was so slight it took dozens of patients across several trials to demonstrate it statistically, that outcome meant sudden death to the idea of marketing the product as an antihypertensive agent.

Pharmaceutical research is difficult, expensive, time consuming, and risky. So our fledgling drug didn't cure malaria and made a lousy antihypertensive, but it was a novel chemical entity yielding extensive improvement in cardiac output. "We've got a fantastic new treatment for congestive heart failure here," we said--or so we hoped.

That time around, the company pursued a simultaneous worldwide regulatory submission that took seven years and half a billion dollars. The drug showed astonishing improvements in cardiac hemodynamic parameters and quality-of-life measures. Study coordinators were brandishing thank-you letters from patients attesting to full and fruitful lives. Before taking the drug, they had been virtually bedridden, unable to walk even a few yards or to climb a single flight of stairs. They were the kind of results that makes the hair on the back of the neck of an idealistic young man tingle-a treatment that could potentially relieve the suffering of millions. Noble stuff.

At that time, it was one of the most intensively researched new CHF treatments ever to reach the market. Although regulatory authorities didn't require it then, we decided to add a multicountry, long-term, 4,000-patient survival trial to the dossier, mostly to jazz up our marketing message.

Unfortunately, we learned something that a lot of other pharma companies and their patients have learned in the years since: Sometimes, adverse events don't show up until thousands of patients try a new drug. Then they instantly appear on the front page of the newspaper and on the nightly news.

Even after studying investigational medical products for years, if not decades, before they reach the market, there is still really no way to know until it's too late what unfavorable reaction might rear its ugly head. Approval from FDA or other regulatory agencies does not guarantee that a new compound has no adverse effects or even that scientists know everything there is to know about it. It simply means that the drug has been adequately tested across a representative sample of the population and that the product's benefits, according to the best economically feasible statistical sampling methods, outweigh the risks associated with its use.

Meanwhile, the consumer press bombards the public with horror stories of how an incompetent FDA was too quick to approve an obviously dangerous product. And before a pharma company can even verify an early report of an unexpected adverse effect, the airwaves are filled with ads for lawyers who promise to stick it to that cold-hearted pharma giant that pushed through a toxic brew in a plot to boost corporate profits.

Give me a break.

The public wants the impossible. Patients want an endless parade of innovative and effective new medical products to be available immediately upon initial discovery, at virtually no cost, with an iron-clad guarantee of no side effects. It's enough to make a former pharmacist abandon his patients to fend for themselves.

But, darn it, there is still that integrity thing. I made a commitment to myself, if not to all of humankind, to help develop cures-or at least safe and effective medical treatments-for all the diseases and discomforts in the world. So what if, in the naiveté of youth, I didn't stop to examine whether my goal was a little too lofty or my scope too grand-iose? It doesn't matter that this is a competitive, difficult, and risky industry or that it is physically impossible to satisfy customers' unyielding desire for a miracle. A promise is a promise.

For Patients and Profits

Our tasks are Herculean, our journey treacherous, and our recognition sometimes dispiriting, but we can't abandon our quest. Maybe not everyone can trace their reason for joining the industry back to some childhood commitment, but many chose a career in medical product development because of the positive impact they could have on millions of people in dire need of help. In the day-to-day events of a complex modern existence, we may lose sight of that admirable, if not entirely altruistic, vision. Still, it remains, lurking in the depths like an anchor line, keeping us moored in our individual, important industry roles. We've still got to find that cure and get it to market for that poor woman with the carpet burns on her fingers , screaming for relief from unbearable pain. A quest cannot be denied.

Of course, stockholders-the people who provide the enormous investments required to conduct medical research-expect, and deserve, to make a profit. This is an expensive and risky business, and all those who invest in it are saints in my book, whether they purchase stock in a public company; invest time, energy, and maybe a little of their souls as pharma company employees; or put their life savings into building a contract research organization from scratch.

And with profit comes competition. Adam Smith's so-called invisible hand theoretically drives investment toward the areas where it will do the most good. Of course, that same hand can also slap you hard across the face, often when you don't even deserve it. I won't claim that it makes anyone stronger in the process. I'm idealistic, not stupid. But in the end, humanity is usually better off with competition than without it. How else would we ever be motivated to quickly develop inexpensive medicines with virtually no side effects?

In the past 15 years, the industry has made great strides in treating intractable headaches and a host of other serious or simply bothersome maladies. After the first few heart-wrenching failures, I helped bring several wonderful products to market, including various therapies for migraine headaches that finally offer my mother some relief. And I've come to recognize that it's just as personally gratifying-although not as financially rewarding-to be part of keeping less-than-perfect drugs off the market as it is to get the better ones there.

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