Increasing Percentages of New Drugs are Failing Phase II and III Trials

In the drug discovery pipeline, Phase I trials are first used to evaluate if a new drug is safe, then Phase II trials are done to assess the drug’s efficacy, and finally Phase III trials are performed to monitor side effects and compare the drug to similar compounds already on the market. Each consecutive phase includes more people to refine the results obtained in the previous phase. A recent analysis by the Centre for Medicines Research in the UK has concluded that since 2008, the failure rate for drugs in Phase II and III clinical trials has been rising [1-2]. Phase II success rates are currently at 18%, lower than at any other phase of drug development.

Drug development pipeline

Synergy Between Antibiotics and Nonantibiotic Drugs

Antibiotic resistance is an ever-growing clinical problem. Four years ago, a study found that antibiotics are overprescribed for sinus infections. Compounding the issue is the fact that as bacteria are learning to tolerate and even circumvent existing classes of antibiotics, not enough work is being done to discover new ones. Combinations or cocktails of antibiotics are often used to broaden the antimicrobial spectrum of each and to achieve synergistic effects; this approach has successfully been applied to combat tuberculosis, leprosy, malaria, and famously, HIV. Yet the discovery of effective combinations has usually been almost fortuitous, most often resulting from trial and error rather than a systematic analysis.

Antibiotic cocktail

In the current study, researchers systematically examined combinations of 1,057 compounds previously approved as drugs to find those that exhibited synergy with the antibiotic minocycline. Their work is reported in the April 24, 2011 issue of the journal Nature Chemical Biology [1]. The compounds were chosen because they have already been approved as drugs, they are known to have activity in vivo and are known to be relatively safe. Many approved drugs are known to have utility for clinical indications other than those for which they initially received approval. Moreover, using pre-approved compounds also reduces the time and cost associated with developing new compounds for therapeutic use.

Sun Exposure, Vitamin D Can Affect Breakdown of Medicines

Genetic variation has been though to be responsible for the differences between people to metabolize certain drugs. The results of a recent study from the Karolinska Institutet in Sweden suggest that it may be even more complicated. Swedish reserchers have found that the body’s ability to break down medicines may be closely related to sunlight exposure and vitamin D, and thus may vary with the seasons. The study, published in the journal Drug Metabolism & Disposition, offers a completely new model to explain individual differences in the effects of drugs [1].

Sunlight can influence the breakdown of medicines in the body

NIH to Establish Translational Medicine Center

Francis Collins, Director of the National Institutes of Health (NIH), said last month that he is moving ahead with a plan to create a new center focused on translational medicine, presently called the National Center for the Advancement of Translational Sciences (NCATS) [1]. The strategy comes at a time of mounting frustration from researchers that the abundance of new information about the molecular basis of many diseases hasn’t led to the development of new therapies.

Translational research

Grand Rounds: the Impact of Healthcare Reform

Welcome to Grand Rounds: the Impact of Healthcare Reform.

There’s a revolution occurring on the Web: those “authoritative” articles written on traditional, static websites are being replaced with blogs, wikis and online social networks. In the sphere of health, medicine and information technology, this “real-time Web” consists of many who are professionals in the field; their posts are listed below. In the digital age, these are the characteristics of new media: recent, relevant, reachable and reliable.

For this edition of Grand Rounds, Vol. 7 No. 11, we’re focusing on the impact of healthcare reform: what are the changes to healthcare delivery, utilization, quality, costs (either as a provider or a patient) and outcomes. After all, these changes affect everyone, whether you’re a patient, a healthcare provider or a biomedical researcher.

Healthcare reform