Target Validation or not
The reproducibility of some target identification/validation studies has been questioned on several occasions and I've flagged up some of the concerns in the Target Validation section of the Drug Discovery Resources. A recent study, reported in Science 28 August 2015: Vol. 349 no. 6251 DOI looking at psychological science, attempted to replicate published work suggests that 39% of effects replicated the original result. Also Amgen, tried to replicate 53 'landmark' cancer studies and failed to replicate the original studies in all but six occasions, Nature 483, 531–533 (29 March 2012) DOI.
A while back a project was initiated to look at reproducibility in cancer, Science Forum: An open investigation of the reproducibility of cancer biology research DOI.
It is widely believed that research that builds upon previously published findings has reproduced the original work. However, it is rare for researchers to perform or publish direct replications of existing results. The Reproducibility Project: Cancer Biology is an open investigation of reproducibility in preclinical cancer biology research. We have identified 50 high impact cancer biology articles published in the period 2010-2012, and plan to replicate a subset of experimental results from each article. A Registered Report detailing the proposed experimental designs and protocols for each subset of experiments will be peer reviewed and published prior to data collection. The results of these experiments will then be published in a Replication Study. The resulting open methodology and dataset will provide evidence about the reproducibility of high-impact results, and an opportunity to identify predictors of reproducibility.
Well some of the early results are in and they make for pretty sobering if not unexpected reading, of the first 7 papers examined, 2 appear to reproduce the original finding to some extent, three show significant differences from the original studies. The results are published in eLife here and there is an editorial here DOI, and they make an important point.
if all the original studies were reproducible, not all of them would be found to be reproducible, just based on chance. The experiments in the Reproducibility Project are typically powered to have an 80% probability of reproducing something that is true.
The key question is of course, is the failure to reproduce these results due to methodological differences not apparent from the described experimental or whether the fundamental result is invalid. At the moment if you are planning to invest in a drug discovery project based on a single publication then Caveat emptor.