1 New drugs are new. To develop a drug from a newly discovered molecule for a hitherto untreated condition is exploring terra incognita. Creating a new drug can mean developing a new biological concept, a new manufacturing process, and a new way of measuring a clinical response. What worked last time may be irrelevant for a new therapy.
2 Men are not mice. Drug discovery usually starts in the laboratory, progresses to animal models, and ends in human trials. But, as an example, the arthritis created by injecting mice with collagen is not really rheumatoid arthritis. Translating what scientists observe in mice to what will actually happen in humans is difficult - and often disappointing.
3 People vary. Laboratory experiments pay great attention to uniformity and control. But the testing of new drugs in humans confronts the defining characteristic of people – their heterogeneity. Beyond differences in sex, age, ethnicity, and drug metabolism, disease itself varies according to severity, preexisting conditions, and the influence of other medications. A drug effect observed in the laboratory is often overwhelmed by the variability of real, living humans.
4 Nature is conservative. The approval rate for new drugs that make it to clinical trials is around 20%, suggesting that something is working actively against new compounds. Human bodies expel foreign molecules, drugs included.
5 Manufacturing drugs is expensive. A new drug needs to be manufactured by new methods, often in a new plant that must pass inspection by regulatory authorities. The investment in such manufacturing facilities and processes must be made years before regulatory approval. Only the drugs most likely to succeed will ever justify this risky investment.
6 Ars longa, vita brevis. Most drugs take around ten years to develop. Human attention is weak over such a long period; markets change, companies run out of cash, and things go wrong.
7 Almost no one knows how to develop drugs. A project may take ten years or more; few people stay in one job for more than about three years. For all these reasons, few researchers have seen the development from beginning to end. There is no academic discipline that prepares people for careers in drug development. Everyone learns as they go. And no one shares what they have learned outside the company.
8 There are no shortcuts. Many assume that opaque regulatory requirements are the main reason it takes so long and costs so much to develop a drug. Not so. Agencies explain clearly what they want to know about toxicology, efficacy, safety, and standards for new drugs. But it simply takes time to accumulate the requisite knowledge about a novel substance.
9 It doesn’t get any easier. As science develops better, more-effective therapeutics, the bar gets higher for the next generation of drugs. When one drug becomes a standard, its successor will likely take longer to develop and cost more.
10 There are no revolutions. Now, as ever, progress in drug discovery is incremental. Understanding the molecular basis of disease will allow the development of specific and more-predictable treatments. Better information systems will help to order the immense amount of data now generated in the laboratory. But neither genomics nor bioinformatics will magically transform drug discovery.
Contributed by Barry Sherman and Philip Ross. Originally published by them in The Acumen Journal of Sciences, Volume I and reprinted with their permission.
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