Corporate Banner
Satellite Banner
Biomolecular Screening
Scientific Community
Become a Member | Sign in
Home>News>This Article

Aptiv Solutions Improves Accuracy of Dose Escalation Studies with Launch of ADDPLAN® DF 3.0

Published: Friday, May 16, 2014
Last Updated: Friday, May 16, 2014
Bookmark and Share
ADDPLAN® DF 3.0 incorporates complex statistical methodologies to prevent under and over-estimation of a therapeutic’s maximum target dose (MTD) during Phase I dose escalation trials.

Accurate estimation of MTD minimises safety and efficacy issues leading to late phase clinical trial failures and is of particular importance for oncology, which has one of the highest Phase III attrition rates among all major therapeutic classes.

“Inaccurate dose selection in Phase I can place a ceiling on drug efficacy in all subsequent phases, potentially dooming a good drug, or expose patients to needlessly high and harmful doses. Operational tools that improve accuracy of Phase I trials is a major objective for drug developers,” says Professor Andy Grieve, Senior Vice President of Clinical Trial Methodology at Aptiv Solutions.

The pharmaceutical industry is well aware that the traditional 3+3 approach, which is still used in more than 95% of Phase I trials, is slow and often underestimates the MTD. Alternative model-based approaches, such as the continual reassessment method (CRM) and the modified toxicity probability interval (mTPI) approach, have broader appeal. Regulatory agencies are supportive of the development of innovative dose escalation procedures. For example, Sue-Jane Wang of the Office of Biostatistics at the FDA co-authored a recent publication in the Journal of Clinical Oncology on the mTPI methodology.

Despite clear advantages, adoption of these model-based approaches has been slow due to the intensive programming required for confident implementation and avoidance of MTD over-estimation. Aptiv Solutions developed ADDPLAN DF 3.0 to provide a validated platform for simulating and comparing dose escalation designs without the need for intensive programming. The software, which benefited from beta testing feedback from ADDPLAN DF Consortium members at Eli Lilly, Janssen, and Novartis, simulates and allows comparison of the 3+3, mTPI, classical CRM, and a modified CRM approach known as Bayesian logistic regression with overdose control. The latter methodology was originally developed by Novartis.

“Several dose escalation methods exist but without a tool to compare these methods, the effectiveness of Phase I studies is significantly reduced. Simulations comparing the impact of dose-response assumptions, dose selection rules, and stopping rules increase the transparency of these methods and help statisticians select the appropriate dose escalation design,” says Grieve. “ADDPLAN DF 3.0 is a robust tool to help resolve dose-related drug failures and supports the industry’s push to adopt innovative design and execution strategies to improve drug development.” 

Executing adaptive designs in Phase I and beyond can require sophisticated logistics and robust firewalls to maintain trial integrity. ADDPLAN DF software provides direct integration with AptivAdvantage®, the leading real-time execution technology platform for seamless implementation of dose adaptations and operational modifications in adaptive design trials.

In addition to its utility for Phase I studies, ADDPLAN DF is the first validated software to utilise the EMA-qualified MCP-Mod methodology for more accurate analysis of Phase II dose-finding designs. The ADDPLAN DF Consortium members are currently collaborating to develop the first toolset for applying the MCP-Mod methodology to adaptive trial designs, expected in late 2014. 

Earlier this year, the FDA, EMA, and PMDA licensed the ADDPLAN family of innovative software for the design, simulation, and analysis of adaptive clinical trials. 

The ADDPLAN DF development team, led by Grieve, has published a white paper on Phase I dose escalation designs, titled “ADDPLAN® DF for Designing More Accurate Dose Escalation Studies in Exploratory Drug Development,” that is available below.

Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,500+ scientific posters on ePosters
  • More than 5,200+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Scientific News
Influential Cancer Researcher Receives Agilent Thought Leader Award
Biologist Scott Lowe receives award in recognition for his contributions to cancer biology.
Startup Seeks More Precise Prostate Cancer Screening
Gregor Diagnostics aims to bring a non-invasive prostate cancer screening test to the market.
Tumor Markers Reveal Lethality Of Bladder Cancers
Researchers found that detection of certain tumor cells in early stage cancers helps identify high-risk cancers.
Preventing "Friendly Fire" in the Pancreas
Researchers inhibit process that leads to the body attacking its own insulin-producing cells.
3D-Printed Heart-On-A-Chip with Integrated Sensors
Researchers have created the first 3D-printed organ-on-a-chip with integrated sensors, paving the way for more complex, customizable devices.
Drug Target for Triple-Negative Breast Cancer Found
A team of researchers led by UC San Francisco scientists has identified a new drug target for triple-negative breast cancer.
Smartphone Laboratory Detects Cancer
Researchers develop low-cost, portable laboratory on a smartphonecapable of analysing multiple samples simultaneously.
First Entirely 3D-printed Organ-on-a-Chip with Integrated Sensors
New approach to manufacturing may allow researchers to rapidly design organs-on-chips that match the properties of a specific disease or individual patient's cells.
Bacterial Genes Boost Current in Human Cells
Borrowing and tweaking bacterial genes to enhance electrical activity might treat heart, nervous system injury.
Targeting Cannabinoid CB2 Receptors in the CNS
With endogenous cannabinoids considered as a potential target to combat CNS diseases, this article examines the role of CB2R could play in fighting some disorders.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,200+ scientific videos