Clinical trials are failing to provide enough reliable evidence on which to base clinical decisions, UK researchers say.
In a commentary in the journal Trials, the team from Oxford University’s Centre for Evidence Based Medicine said clinical trial outcomes commonly failed to translate into clinical benefits for patients.
They said the use of surrogate, composite or subjective outcomes – often cheaper and faster to measure – undermined the quality of clinical trial findings.
Similarly complex clinical scores and non-validated rating scales created from combinations of symptoms ands signs could skew research findings.
“Clinical trials require rating scales that are rigorous, but this is difficult to achieve,” they said.
“Moreover, patients want to know the extent to which they are free of a symptoms or a sign, more so than the mean change in a score.”
They also called out errors in trial implementation and interpretation such as missing data, poorly specified outcomes, publication or reporting bias, underreporting of adverse events, and use of relative instead of absolute measures.
Professor John Simes, director of the NHMRC Clinical Trials Centre at the University of Sydney, said the commentary provided a useful checklist of potential pitfalls for researchers.
However he disagreed that trials were failing to translate into benefits for patients and said there had been many initiatives to improve the process.
“I wrote one of the early papers on publication bias in 1986 which called for clinical trials registries to get less distortion into the system. It took 15-20 years to set up those registries but we now have a standard approach for every trial.”
The GRADE criteria used for assessing clinical trials was another example of continuous improvement by the clinical research community.
Professor Simes said clinical trials were becoming more complex as they increasingly built in translational science including blood and tumour markers.
“Especially now that we have ability to collect so much more biological material to classify the nature of disease, to measure a treatment effect in different sub-groups requires an additional layer of complexity.”
He said the judicious use of surrogate markers or various modeling techniques were usually done with the best of intentions including ethical concerns for trial participants who may have failed on one treatment and required a salvage therapy.
“The fault often lies not in individual trials but in their interpretation,” he said.
However the peer review process ensures there is appropriate capture of all necessary information, he added.