As with any new process, but especially one involving drug or treatment development, there were a significant number of factors to be considered when adaptive studies were developed in order to ensure they were an improvement over conventional clinical studies rather than seeming like they were because of the time and cost efficiencies alone.
Conventional Clinical Studies
Traditionally in clinical studies the critical parameters are completely pre-planned. To do this assumptions are made and best estimates used for parameters such as population averages, dose-response effect size, variation due to location, etc. When estimates are accurate the study design can work well, and when they are not accurate the study suffers.
To overcome this uncertainty, conventional studies include methodologies that reduce the impact of the unknown. That often means multiple randomised samples and a lot more participants over a long time to ensure the study is accurate. For example, this can mean that when compared to adaptive phase 1 studies, significant numbers of people receive treatment with doses of drugs that are not optimal, and so their recovery is affected.
Adaptive Clinical Studies
When adaptive phase 1 studies are conducted there is a large degree of flexibility built into the planning phase. A number of different parameters can be adapted such as drug dosage, sample size and location and eligibility criteria as well as many more factors. A thorough description can be found here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830330/.
It could sound like decisions to adapt a clinical trial can be taken on the spot. In fact, all adaptations must be planned in advance and designed into the study and reviewed as it progresses. However, the significance of the adaptive phase 1 approach is that undesirable delays and costs can be avoided, as explained at https://www.richmondpharmacology.com/specialist-services/adaptive-phase-i-studies.
One of the pitfalls of adaptive phase 1 clinical studies is the potential for bias can be introduced. This could occur due to a number of factors – the most common being more that one parameter being adapted during the study. Any such bias can lead to a greatly increased time to market due to needing to revisit work that should have already been completed.
Overall, the use of adaptive clinical studies has become preferred over conventional studies. Designed carefully, in advance, they bring massive time and cost savings.
