Drug Discovery: Are Business and Science Diametrically Opposed?
The business and science of innovation are challenged by a recent article in British Medical Journal entitled "Pharmaceutical research and development: what do we get for all that money?"
The business and science of innovation are challenged by a recent article in British Medical Journal entitled “Pharmaceutical research and development: what do we get for all that money?”
Pharmaceutical companies’ research and development (R&D) strategies have come under scrutiny with the release of a new report by Donald W. Light, PhD, MS, and Joel R. Lexchin, MD, MSc, published in the August 7, 2012, edition of British Medical Journal. Despite widespread media reports that it has become increasingly difficult to develop and discover new molecular entities, these authors purport that the real issue behind the perceived lack of scientific innovation is that the drugs in which the pharma industry is investing are “clinically minor” and don’t represent a real therapeutic advantage for patients.
Dr. Light is a psychiatry professor at the University of Medicine and Dentistry of New Jersey, a visiting researcher at Princeton, a network fellow at Harvard University, and a senior fellow at the University of Pennsylvania's Center for Bioethics. Dr. Lexchin works at the School of Health Policy and Management at York University in Toronto. They have each done many health research studies about the cost of developing medicines, some of which were used to support their argument in their most recent BMJ article.
Focus on R&D
Citing research from various sources, Drs. Light and Lexchin argue that pharmaceutical companies have a hidden agenda when it comes to deciding which drug targets to pursue. Rather than focusing on the development of therapeutically and pharmacologically innovative materials, the authors allege that pharmaceutical companies are too heavily invested in churning out variations of existing drugs in order to secure company profits. They also state that often these drugs do not substantially benefit patients. They note that of the 218 drugs that received FDA approval from 1978 to 1989, only 34 were determined in a study to be therapeutically important. “The low bars of being better than placebo, using surrogate endpoints instead of hard clinical outcomes, or being noninferior to a comparator, allow approval of medicines that may even be less effective or less safe than existing ones,” the authors noted.
The problem with the current pharmaceutical business model, according to the authors, stems from the lack of funds allocated to the discovery of new molecules. Drs. Light and Lexchin claim that based on data extracted from company and government reports, companies were found to spend only 1.3% of revenues on basic research. The ratio of money spent on basic research to marketing is 1:19. According to the authors, profits depend more on the extension of existing patents and the restriction of free market competition from generics than on breakthrough research.
The answer to making safer, more cost effective pharmaceuticals relies on fewer approvals, Drs. Light and Lexchin write. They believe that restricting the approval of products to those that are medically necessary will force drug companies to address unmet medical need. They also suggest the exploration of a market incentive that differs from that of traditional patent protection: drug innovation would be rewarded by large cash prizes rather than by patent royalties.
Building a Sustainable Pharmaceutical Model
Many business analysts and patient advocates would agree with the authors’ conclusion that pharmaceutical companies are more motivated to develop financially lucrative medications than less profitable but more globally impacting medical solutions. In a lecture unrelated to the study, Thomas Pogge, PhD, director of the Global Justice Program, Leitner professor of philosophy and international affairs at Yale University, and founder of The Health Impact Fund, noted that 90% of pharmaceutical research accounts for just 10% of the global burden of disease, whereas 10% of pharmaceutical research accounts for 90% of the global disease burden. He asserts that the patent process stunts universal access of many useful pharmaceutical innovations. But, Dr. Pogge concedes in a TEDxCanberra video that pharmaceutical companies need to charge higher prices for their drugs in order to remain sustainable. He believes that drug companies should have the option to either make their money through patent-protected mark-ups, or be rewarded based on the health impact of the drug they have created.
Despite evidence presented by Drs. Light and Lexchin suggesting that drug companies are restricting innovation through their marketing strategies, scientists who have worked directly on drug discovery, such as Derek Lowe from the blog In the Pipeline, disagree with most of the authors’ assertions in the BMJ report. Dr. Lowe contests that contrary to the opinions in the article, researchers have the desire to discover new molecular entities that demonstrate substantial clinical benefits. He says that no researcher ever sets out to fail, but unfortunately, failures do occur during drug trials. Researchers often identify a therapeutic target in their quest for a disease “cure,” but there is no guarantee that the drug will be effective or work differently than existing therapies until it is tested in human trials. Sometimes the journey to finding an effective treatment relies on minor, incremental advances, Dr. Lowe emphasized. When dealing with chronic disease, some sort of efficacy is better than no efficacy.
Dr. Lowe also points out, like Dr. Pogge, that marketing a drug is necessary to its survival, and marketing, in principle is meant to create a profit. Spending money on marketing helps makes the drug generate revenue and balances out the largely unprofitable business of research and development. “Complaining that the marketing budget is bigger than the R&D budget is like complaining that a car’s passenger compartment is bigger than its rudder,” wrote Dr. Lowe in a blogpost.
Finding a Drug Target is Just the Beginning
Neither the BMJ article, nor the criticisms it drew, offered guidelines by which “successful” drugs should be measured or judged. Is the extension of life by a few months enough for a drug to be considered a success, even if the drug does nothing to prevent disease progression? Proving the value of a new molecular therapy usually occurs late in the development game, and much is invested in this process.
What we do know is that scientific inquiry and pharmaceutical innovation are not always predictable—and sometimes, the drug discovery process reveals the wrong answers. The trend in clinical studies is currently on personalized medicine and the discovery of riskier, genomics-based candidates. Discovering a potential drug target, although exciting, is just the beginning of the (expensive) R&D process, notes Dr. Lowe. We are pushing the limits of our current scientific understanding of the major disease related biological pathways, and solving the productivity challenge requires an increase in the rate of basic scientific discovery and biological understanding.
Perhaps medications that are considered “clinically minor” by some have been awarded FDA approval because they were easier to develop or had more discrete clinical end points; these factors would effectively make a drug’s clinical impact simpler to evaluate. The inherent complexities of genomics-based drug candidates and the chronic diseases they treat should be considered when evaluating the health impact of a medication and the strategies that were employed in the search for clinically major, blockbuster pharmaceuticals.