The sole purpose of introducing adaptive clinical trial design is to provide flexibility for identifying optimal clinical benefits of test drug without compromising ethical and scientific aspects of research.
Benefits of Adoptive Clinical Trial
- Research question getting answered: by embracing the modification in research protocol, chances of research question getting answered is enhanced even in unanticipated unfavorable situation. But, it doesn't guarantee any positive outcome.
- New drug development becomes less time consuming with improvement in overall success rate
- Combats the common difficulties during drug development like low success rate, specially pharmaceuticals funded trials, procedural complexity, rapid escalation of cost, decreased willingness of bringing new candidates forward by the existing one and so on.
- Overall process becomes more flexible, efficient and less time consuming
Methodology of Adaptive Clinical Trial Design
Planning for adaptation is normally made before the data was examined in unblinded manner, but process actually starts once interim analysis completes with data in hand (Interim analysis is generally performed when 50 % of research work is completed).
Notably, changes in research design as well decision not solely based in internal reason is not considered to be adaptive at all.
Obtained Data is transferred to Data Safety Monitoring Board (DSMB) for analysis, they check for major or minor discrepancies, if present, impact on future study result, study participant and possible legal threats are also analysed. Message is circulated to sponsor, with the prior notification to ethics committee. Final decision on making protocol amendments and giving the shape of adaptive trial design is performed by Sponsor.
Protocol amendment consists mainly of two procedure viz. trial procedure and statistical procedure. Trial procedure includes Eligibility criteria, study dose, treatment duration, study endpoint, laboratory testing procedures, diagnostic procedures criteria for evaluation and assessment of clinical responses. Whereas Statistical procedure includes Randomization, study design, hypothesis, sample size, data monitoring and interim analysis, methods of data analysis.
Though there are various models used as adaptive methods in clinical trial, the most commonly used one in clinical trial are as follows:
Notably, changes in research design as well decision not solely based in internal reason is not considered to be adaptive at all.
Obtained Data is transferred to Data Safety Monitoring Board (DSMB) for analysis, they check for major or minor discrepancies, if present, impact on future study result, study participant and possible legal threats are also analysed. Message is circulated to sponsor, with the prior notification to ethics committee. Final decision on making protocol amendments and giving the shape of adaptive trial design is performed by Sponsor.
Protocol amendment consists mainly of two procedure viz. trial procedure and statistical procedure. Trial procedure includes Eligibility criteria, study dose, treatment duration, study endpoint, laboratory testing procedures, diagnostic procedures criteria for evaluation and assessment of clinical responses. Whereas Statistical procedure includes Randomization, study design, hypothesis, sample size, data monitoring and interim analysis, methods of data analysis.
Types of Adaptive designs in Clinical Trials
Though there are various models used as adaptive methods in clinical trial, the most commonly used one in clinical trial are as follows:
- Adaptive Randomization Design: Randomization process is not fixed so that probability of treatment assignment changes over time considering previously enrolled patient. There should be recalculation of treatment assignment probability, but it is predetermined and no changes are entertained in fixed randomization.
- Group sequential design: Sample size of the patient is not previously fixed, can be added, reduced or suspended based upon the result of interim analysis. Considerations are made on the basis of efficacy and safety reports of trial participants. Data Safety Monitoring Board (DSMB) plays the key role for suggesting sponsor to make such changes or in extreme finding trial can be terminated prematurely. For example: In Oncology setup, number of participants are added over time following sequential pattern like 3 + 3.
- Drop the loser Design: Here, subjects receiving inferior treatment can be dropped by adopting new treatment arm. Again decision is made on the basis of interim analysis report, such model is commonly applied for phase-II clinical development study.
Conclusion
Adaptive Clinical Trial Design is progressively advancing and widely accepting model, found to be effective in terms of reducing the time and cost of large scale Drug development Research with enhancing the scientific pragmatism of study. With considering various factors like statistics, research ethics, business need and benefits of trial participants, various Regulatory authorities has been adopted the model to make the Research Process more beneficial to needy ones and Rational to the scientific communities.
Thank You !!!
References:
https://newonlinecourses.science.psu.edu/stat509/node/68/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2941608/
https://www.eupati.eu/glossary/group-sequential-design/
https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-018-1017-7
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