Barriers and opportunities for implementation of adaptive designs in pharmaceutical product development
Abstract
Background This review discusses barriers to implementing adaptive designs in a pharmaceutical R&D environment and provides recommendations on how to overcome challenges. A summary of findings from a survey conducted through PhRMA’s working group on adaptive designs is followed by a report based on our experience as statistical and clinical consultants to project teams charged with establishing the clinical development strategy for investigational compounds and interested in applying innovative approaches.
Findings and recommendations Adaptive designs require additional work in that clinical trial simulations are needed to develop the design. Some project teams, due to time and resource constraints, are unable to invest the additional effort required to conduct necessary scenario analyses of options through simulation. We recommend formally integrating the planning time for scenario analyses and to incentivize optimal designs (e.g., designs offering the highest information value per resource unit invested). Regardless of the trial design ultimately chosen, quantitatively comparing alternative trial design options through simulation will enable earlier and better decision making in the context of the overall clinical development plan. Adhering to ‘Good Adaptive Practices’ will be key to achieving this goal.
Outlook Implementing adaptive designs efficiently requires top—down and bottom— up support and the willingness to invest into integrated process and information technology infrastructures. Success is conditional on the willingness of the R&D environment to embrace the implementation of adaptive designs as a Change Management Initiative in the spirit of the Critical Path of the Food and Drug Administration. Clinical Trials 2010; 7: 167—173. http://ctj.sagepub.com
Get full access to this article
View all access and purchase options for this article.
References
Krams M., Sharma M., Dragalin V., et al. Adaptive approaches in clinical drug development. Opportunities and challenges in design and implementation. Pharm Med 2009; 23: 139-48.
Bretz F., Branson M., Burman CF, et al. Adaptivity in drug discovery and development. Drug Dev Rev 2009; 70: 169-90.
Gallo P., Chuang-Stein C., Dragalin V., et al. Executive summary of the PhRMA working group on adaptive designs in clinical drug development. J Biopharm Stat 2006; 16: 275-83.
Gallo P., Krams M. PhRMA working group on adaptive designs: introduction to the full white paper . Drug Info J 2006; 40: 421-3.
Quinlan JA, Krams M. Implementing adaptive designs: logistical and operational considerations. Drug Info J 2006; 40: 437-44.
Fardipour P., Littman G., Burns D., et al. Planning and executing response-adaptive learn-phase clinical trials: 1. The process. Drug Info J 2009; 43: 713-23.
Gaydos B., Anderson K., Berry DA, et al. Good practices for adaptive clinical trials in pharmaceutical product development. Drug Info J 2009; 43: 539-56.
Gallo P. Confidentiality and trial integrity issues for adaptive designs. Drug Info J 2006; 40: 445-50.
Chmp. CHMP reflection paper on ‘‘Methodological issues in confirmatory clinical trials planned with an adaptive design.’’ Available at: www.emea.europa.eu/pdfs/human/ewp/245902enadopted.pdf . (accessed 20 December 2009).
Dragalin V. Designing, monitoring, and modifying an adaptive trial. Am Pharm Outsourc 2008; 9: 12-16.
Enas G., Anderson K., Bedding A., et al. Global harmonization of standards for adaptive clinical trial designs. Regul Focus 2008; 13: 8-17.
Chuang-Stein C., Bretz F., Komiyama O., Quinlan J. Interactions with regulatory agencies to enhance the understanding and acceptance of adaptive designs. Regul Focus 2009; 14: 36-42.
Dick Clark in an interview with the Financial Times 2006. Available at: http://www.ft.com/cms/s/0/e7bde0ee-bb4d-11da-8f51-0000779e2340.html?nclick_check=1 . (accessed 20 December 2009).
Cite article
Cite article
Cite article
OR
Download to reference manager
If you have citation software installed, you can download article citation data to the citation manager of your choice
Information, rights and permissions
Information
Published In
Article first published online: March 25, 2010
Issue published: April 2010
PubMed: 20338900
Authors
Metrics and citations
Metrics
Article usage*
Total views and downloads: 209
*Article usage tracking started in December 2016
Altmetric
See the impact this article is making through the number of times it’s been read, and the Altmetric Score.
Learn more about the Altmetric Scores
Articles citing this one
Receive email alerts when this article is cited
Web of Science: 44 view articles Opens in new tab
Crossref: 47
-
Feasibility of a Platform Trial Design for the Development of Mobile H...
-
Reporting quality was suboptimal in a systematic review of randomized ...
-
Point estimation for adaptive trial designs I: A methodological review
-
Design and implementation of an adaptive confirmatory trial in Japanes...
-
The adaptive designs CONSORT extension (ACE) statement: a checklist wi...
-
Stakeholder perspectives on adaptive clinical trials: a scoping review
-
The Adaptive designs CONSORT Extension (ACE) statement: a checklist wi...
-
A review of available software for adaptive clinical trial design
-
Changing platforms without stopping the train: experiences of data man...
-
Designing and conducting proof-of-concept chronic pain analgesic clini...
-
Adaptive Designs: Results of 2016 Survey on Perception and Use
-
Adaptive designs in clinical trials: why use them, and how to run and ...
-
Development process of a consensus-driven CONSORT extension for random...
-
Efficiency Considerations for Group Sequential Designs with Adaptive U...
-
Practical characteristics of adaptive design in phase 2 and 3 clinical...
-
The Real‐World Ethics of Adaptive‐Design Clinical Trials
-
A conceptual model for the development process of confirmatory adaptiv...
-
DIA’s Adaptive Design Scientific Working Group (ADSWG)...
-
Targeting PI3K/AKT/mTOR Pathway
-
Adaptive designs undertaken in clinical research: a review of register...
-
Attitudes and opinions regarding confirmatory adaptive clinical trials...
-
CBER’s Experience With Adaptive Design Clinical Trials
-
Missing steps in a staircase: a qualitative study of the perspectives ...
-
Cross-sector surveys assessing perceptions of key stakeholders towards...
-
An Investigation of the Shortcomings of the CONSORT 2010 Statement for...
-
Sample Size Re-estimation Designs In Confirmatory Clinical Trials—Curr...
-
Book Reviews
-
Effective Drug Supply for Adaptive Clinical Trials...
-
Adaptive Design: Results of 2012 Survey on Perception and Use
-
Precision Medicine Clinical Trials: Defining New Treatment Strategies
-
The Need for and the Future of Adaptive Designs in Clinical Developmen...
-
Implementation Issues in Adaptive Design Trials
-
INHANCE: An Adaptive Confirmatory Study with Dose Selection at Interim
-
Targeting the PI3K/AKT/mTOR and Raf/MEK/ERK pathways in the treatment ...
-
Bayesian adaptive trials offer advantages in comparative effectiveness...
-
On the choice of doses for phase III clinical trials
-
Overview, hurdles, and future work in adaptive designs: perspectives f...
-
Panel discussion 1
-
An Overview of the Adaptive Designs Accelerating Promising Trials Into...
-
Sample size re-estimation in an on-going NIH-sponsored clinical trial:...
-
Bayesian adaptive clinical trials: a dream for statisticians only?
-
The Sequence of Clinical Development
-
Adaptive Design Across Stages of Therapeutic Development
-
Implications of comparative effectiveness research for radiation oncol...
-
Food and drug administration′s critical path initiative and innovation...
Figures and tables
Figures & Media
Tables
View Options
Get access
Access options
If you have access to journal content via a personal subscription, university, library, employer or society, select from the options below:
loading institutional access options
SCT members can access this journal content using society membership credentials.
SCT members can access this journal content using society membership credentials.
Alternatively, view purchase options below:
Purchase 24 hour online access to view and download content.
Access journal content via a DeepDyve subscription or find out more about this option.
