The successful application of adaptive designs to clinical trials can cut anything from months to a year off trial times, a new study has found.
Nearly 60% of executives surveyed for the study told Cutting Edge Information that adaptive designs shortened trial duration, with an average of three months saved but with one company completing its trial one year faster, the researchers reported.
Another 13% of the executives said, though, that adaptive designs lengthened trials, while around a quarter felt the adaptive design approach did not have any impact on trial duration.
Adaptive trial designs allow sponsors to adjust parameters such as dose selection or sample size in the light of accumulating safety or efficacy data. The aim is to accelerate clinical development and improve its efficiency, better target experimental therapies to responsive patient groups, and reduce the number of patients exposed to inappropriate or ineffective drugs.
The Cutting Edge Information study, Clinical Operations: Per-Patient Trial Costs, Staffing and Adaptive Design, also concluded that high-level executive support and wider acceptance of flexible trial designs are needed to drive better usage.
To date, development teams have generally used adaptive designs in limited ways, with many only applying the strategy in early-stage trials, the researchers noted.
Regulatory concerns, problems with supply-chain management and the challenges of understanding and implementing complex statistical methodologies have previously been cited as some of the barriers to a more dynamic uptake of adaptive clinical trials.
The draft guidance for industry on adaptive trial designs issued by the US Food and Drug Administration in February 2010 may go some way towards easing these concerns.
A European USP?
Speaking at the recent 32nd Annual Conference & Exhibition of the UK’s Institute of Clinical Research in Brighton, Dennis Joseph, area head, clinical operations Europe for Pfizer, described the company’s use of adaptive designs as “very patchy”, depending heavily on the therapeutic area in question and the views of regulators.
“We’ve seen actually relatively few adaptive designs” put into place at Pfizer, Joseph commented, citing the need for systems and processes that allow for rapid adjustments, such as electronic case report forms and a “constant flow” of data.
Ignazio Di Giovanna, director of UK-based contract research organisation CCA (Campbell Charles Associates) 2000, painted a similar picture, saying the company had not seen many adaptive designs come through lately and that “the need for good technology” was paramount.
Giovanni did suggest, however, that adaptive designs could be a point of differentiation for Europe in stemming the outflow of clinical trials to emerging markets. “Adaptive designs are particularly well suited to Europe because of our high level of technology, high level of experience and generally well-educated patients,” he said.
For Brendan Buckley, professor of pharmacology and medicine at the University College Cork in Ireland, though, the technology still has a long way to go. He asked “whether we have done anything within the conduct of clinical trials which could not be done” on a Sinclair ZX Spectrum microcomputer nearly 30 years ago.
“We have been absolutely astonishingly slow at moving forward with information technology, other than bits of window-dressing here and there,” Buckley argued. It could still take three weeks on average to get electronically generated data into a database for oncology trials, by which time a “significant proportion” of patients were dead, he pointed out
Until the clinical research sector caught up with the rest of society on the IT revolution, “we haven’t a hope of smartly designing and smartly controlling clinical trials”, Buckley warned.