A commentary published in Cell last month discusses how the quality of communication between and within institutions influences how successfully promising biological findings are translated into novel drug therapies.1
In the commentary it is suggested that most drug development programs which are ultimately successful proceed via a standard approach (Figure 1). In this figure the authors describe the steps involved in a typical drug development program and highlight key communication challenges associated with each.
Figure 1. Communication Challenges Associated with the Process of Drug Development1
The first major challenge identified is regarding candidate therapeutic targets and lead compounds being “oversold” or published with insufficient technical review such that there is a high attrition rate when results cannot be replicated or confirmed by other researchers. A study is given as an example in which Amgen scientists attempt to confirm results from dozens of cancer research publications and only succeed in replicating the findings in six of 53 cases.2 Similar stories are all too familiar, and while the causes are still being widely discussed, the communication failure is very evident.
Attempts to address this issue have begun with changes to the manuscript review process. Some journals are employing a checklist for authors, intended to document the rigor with which experiments are conducted, e.g. Nature: Reporting Checklist For Life Sciences Articles, and other editors have expressed interest in having statisticians consult on certain manuscripts. As the authors point the finger particularly at academic research, they suggest that industry-based scientists with technical expertise be engaged, both in reviewing drug discovery reports and in consulting throughout projects. Although they acknowledge that nowadays experts with relevant knowledge are often embedded within academic institutions. In addition they suggest that editors should insist that reports include an honest communication of any limitations of novel targets or inhibitors but emphasise that this should not preclude publication.
The second challenge is associated with how drug discovery projects are executed. Typically the teams responsible for driving projects are comprised of an array of scientists from biology, medicinal chemistry, biochemistry, structural biology, etc. Although they share a common goal because each scientist is an expert trained in their specific discipline they often speak in different “languages”. The authors highlight that teams are required to make many pivotal decisions and suggest that these can only be well informed where experts avoid use of jargon such that all team members can understand and examine the vital information. They also propose that it is as important to communicate experimental failure as it is success. Appropriate scrutiny early in the day should translate into an improved success rate. Given as an example is an analysis of AstraZeneca’s drug development pipeline, which revealed that 40% of the projects classified as efficacy failures in Phase II were associated with a failure to link the molecular target to the intended disease indication.3
Thirdly the authors highlight a challenge regarding selecting the correct patient population as drugs enter clinical development. The PARP inhibitor, olaparib, is used as an example. Despite olaparib originally being shown to confer synthetic lethality in cancers with BRCA1 and BRCA2 mutations,4 initial clinical development utilised a larger, heterogeneous population and the inhibitor failed to demonstrate good efficacy, regrettably delaying the approval of the drug. Improved communication could have prevented this. To address the issue, the National Centre for Advancing Translational Science has been established within the National Institutes of Health (NIH) to “transform the translational process so that new treatments and cures for disease can be delivered to patients faster”. It is suggested that educating future researchers and physicians in interdisciplinary science to improve communication will prove key to the success of precision medicine.
Finally the authors note that the biomedical community must better communicate with the public in attempt to explain the disappointing success rate of expensive drug development programs.
While disease biology is poorly understood it is inevitable that clinical experimentation will remain unpredictable. However, this commentary convincingly suggests that improved communication throughout the drug discovery process will improve efficiency and increase the likelihood of success.
Blog written by Katie Duffell
- Settleman, J. & Cohen, R. L. Communication in Drug Development : ‘“ Translating ”’ Scientific Discovery. Cell 164, 1101–1104 (2016). doi:10.1016/j.cell.2016.02.050
- Begley, C. G. & Ellis, L. M. Drug development: Raise standards for preclinical cancer research. Nature 483, 531–533 (2012). doi:10.1038/483531a
- Cook, D., Brown, D., Alexander, R., March, R. & Morgan, P. Lessons learned from the fate of AstraZeneca’s drug pipeline: a five-dimensional framework. Nat. Rev. Drug Discov. 13, 419–431 (2014). doi:10.1038/nrd4309
- Bryant, H. E. et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434, 913–918 (2005). doi:10.1038/nature03443