New techniques and technologies for streamlining and accelerating clinical development, along with increasing demand for post-marketing studies, should give industry some relief from escalating R&D costs and the clinical trials sector a platform for strong growth in years to come, a new report predicts.
Among these innovations are microdosing or Phase 0 clinical trials and adaptive trial designs, notes the report by US-based Arrowhead Publishers. The former strategy involves testing trace doses (e.g., 1% or 100 micrograms of the pharmacological dose) in humans to evaluate pharmacokinetics and drug metabolism before a new compound enters Phase I trials. The aim is to speed up drug discovery, identify failures sooner and cut study costs by weeding out candidates with short half-lives or poor bioavailability.
As the methodology and technology for Phase 0 trials become more sophisticated, human microdosing may be applied to a number of compounds that could potentially be administered consecutively, suggests the report on Innovations and Trends in Clinical Trials. Moreover, microdosing could be useful for discovering endogenous biomarkers that would help in the quantitative evaluation of a drug’s in vivo effects.
Using adaptive clinical trials
While adaptive clinical trials – more flexible study formats that employ interim analyses to fine-tune parameters such as dose selection, treatment duration or sample size – clearly have advantages over traditional studies, they are not yet commonplace, mainly due to the complexity of their design, implementation and analysis, the researchers note. In the long term, however, the trend of combining adaptive designs with the goals of Phase IIb and Phase III trials is likely to become the norm, they believe.
This type of ‘seamless adaptive’ study will seek to maximize time efficiencies, although it “may carry higher risks for first-in-class drugs”, Arrowhead comments. It also foresees further consolidation of the clinical trial process. As Phase 0 studies become more routine and desirable, Phase I “will morph into a shorter testing phase, while Phase II and III are likely to merge”. This latter advance would build on a trend already observed in the field, the researchers add, with “many trials designed to test efficacy and safety of the drug at the same time”.
Another transforming factor has been the development of information technology in clinical development, through tools such as clinical trials management systems, electronic data capture and clinical data management systems. The benefits of these technologies can be seen in development times, ease of patient recruitment and retention or the ability to collate information from a wider geographical area. Moreover, the need for faster collection and analysis of all data types has heightened by the increased use of adaptive trial designs, the report observes.
Phase IV post-marketing studies are becoming an increasingly standard feature of the clinical trials landscape, the researchers point out. This trend is being driven not only by closer regulatory scrutiny of drug safety but by companies themselves “finding that Phase IV can help them circumvent costly trials associated with filings for approval for new indications of existing drugs”.
The report forecasts that post-marketing trials will continue to grow at an estimated rate of more than 20% per year. More and more, it suggests, they will be used to expand a drug’s indications and geographical reach while disseminating information to healthcare professionals, regulatory authorities and patients.