Editorial

Where will new drugs come from?

Drugs have to demonstrate efficacy and safety and both need to be integrated into a risk–benefit analysis. As there is no precise way to calculate a risk–benefit profile, drug development and approval remain an art rather than a science. Beyond the strength of data, many other factors have to be taken into account. These include current medical needs, variable regulatory contexts, changing legislative and societal environments, tougher operational challenges and higher costs of investment before any potential return. As was the case in the 1990s with AIDS, targeted treatment for oncology and for orphan diseases are now leading the path to innovations and approvals. Breaking old dogmas, new study designs are attempted. Regulations, such as orphan drug designations, breakthrough therapy, or approval under exceptional circumstances stimulate investment and bring flexibility to the approval process. Because of these, the recent trend indicating a decrease in drug approvals is being corrected.

Medical innovation in developed countries has been linked to burden of disease, with more innovation in areas representing greater investment return. This study used horizon scanning or early awareness and alert activity as a novel measure of innovation to determine whether new and emerging health technologies reported by international horizon scanning agencies reflected diseases constituting the greatest burden.

This was a retrospective observational study of the 20 member agencies of EuroScan (the International Information Network on New and Emerging Health Technologies), representing 17 developed countries. Burden of disease was defined as disability-adjusted life-years, taken from the 2004 World Health Organization Global Burden of Disease estimates. This analysis focused on 102 specific diseases within 21 broader groups. Horizon scanning output was measured as the number of technologies reported by EuroScan member agencies between 2000 and 2009.

At best there was a weak association between innovation and burden of disease. An apparent high-level association was dependent on just three high-prevalence disease groups: malignant neoplasms, neuropsychiatric conditions, and cardiovascular disease. Disaggregating broader groups into specific diseases further weakened the association. Innovation is disproportionately strong in cancer and nonischemic heart disease and disproportionately weak in mental health.

Innovations reported by early awareness and alert systems do not always reflect conditions accounting for the highest morbidity and mortality. The results do not support previous reports of a positive relationship between burden of disease and innovation, but accord with evidence of notable discrepancies among key groups. Factors other than disease burden drive innovation.

After years of hesitation a larger number of pharmaceutical and biotech companies are now supporting the idea of a more individualized pharmacotherapy. The companies that are now involved in this research-demanding area will have to face several challenges. The key factor for success will be an in-depth molecular understanding of the pathophysiology and the mechanism of the drug under development. The one-disease-one-drug-one-target paradigm that has been prevailing for decades is history. Most diseases are heterogeneous and based on molecular profiling they can be divided into biological subgroups that each requires a specific pharmacological intervention.