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

Aptiv Solutions ADDPLAN® DF is the First Validated Software to Use MCP-Mod Methodology

Published: Thursday, October 31, 2013
Last Updated: Thursday, October 31, 2013
Bookmark and Share
MCP-Mod methodology was recently qualified by EMA for reducing bias and error in dose finding clinical trials.

Aptiv Solutions announce that the European Medicines Agency (EMA) has issued a qualification opinion finding that the MCP-Mod1 methodology for dose finding provides the potential to “enable more informative Phase II study designs” and “provide a more solid basis for all subsequent dose selection strategies and decisions”. MCP-Mod is a core component of Aptiv Solutions ADDPLAN® DF software, currently the only validated commercial software available for this methodology.

Estimating dose-response and selecting the appropriate dose for Phase III trials is one of the most difficult challenges of the drug development process, according to the EMA. Currently half of Phase III trials fail, in part because of sub-optimal and inefficient practices for dose selection in Phase II. Current approaches for estimating the target dose are also prone to uncertainty, which can result in the use of an inappropriate statistical model that over- or under-estimates the true effective dose.

“Regulatory agencies and drug developers are concerned with safety and tolerability if the dose is too high and inadequate efficacy if the dose is too low. Accurately defining this risk/benefit ratio is critical to the clinical development process, both to ensure patient safety and the successful approval of groundbreaking medications,” says Professor Andy Grieve, Senior Vice President, Clinical Trial Methodology for Aptiv Solutions.

The MCP-Mod approach is unique in that it defines several plausible candidate dose-response models, tests them for significance, and then identifies the most appropriate statistical approach to model dose-response and estimate the target dose. 

In the extensive simulations reviewed for the qualification opinion, the EMA found that the MCP-Mod methodology appears to be better than the common pairwise ANOVA-based approach in terms of bias and absolute error. “ANOVA approaches work well if the true dose response model is linear, but many drugs do not behave this way,” says Grieve. For other common dose-response relationships, such as a non-linear Emax scenario, the EMA found the ANOVA approach is always among the worst methods to estimate dose response. The EMA also identified that MCP-Mod controls the Type 1 error rate and is less likely than a pairwise ANOVA-based approach to identify a clinically relevant dose in the absence of true dose-response.

“This is a significant shift for the industry. The EMA opinion challenges the way most dose finding studies are performed, essentially saying that the number of doses and the dose range selected are sub-optimal. This leads to poor selection of the effective dose at Phase II, which causes significant problems in subsequent clinical trials,” says Grieve. 

ADDPLAN® DF is a fully-validated design and analysis tool based on MCP-Mod and covers dose finding designs for establishing Proof of Concept and determining the optimum target dose to select for Phase III trials.

In July, ADDPLAN® DF was pre-released in beta version to a top 10 pharma company that served as the prime development partner for the software. The fully validated version launched in September. Two additional top 10 pharma customers are now using the software as founding members of the ADDPLAN® DF Consortium announced earlier this year. 

This release of ADDPLAN® DF is the first in a series of novel methodologies from Aptiv Solutions for use in Phase II clinical trials. 

The white paper titled ‘ADDPLAN® DF - An Advanced Tool for Optimizing Dose Selection in Exploratory Drug Development’ is available below:

Further Information
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 2,700+ scientific posters on ePosters
  • More than 3,800+ 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.

Related Content

Aptiv Solutions to be Acquired by ICON
Combined companies provide unrivalled capabilities for adaptive and medical device trials worldwide.
Monday, March 31, 2014
Tufts CSDD Study Finds Adoption of Adaptive Clinical Trial Designs is Increasing
Report shows growing acceptance by pharmaceutical companies and regulatory agencies.
Friday, May 24, 2013
Aptiv Solutions Growing: Opens New Office in North Carolina
New office is located at 4505 Emperor Boulevard in the Imperial Center.
Monday, December 10, 2012
Scientific News
New Therapy Reduces Symptoms of Inherited Enzyme Deficiency
A phase three clinical trial of a new enzyme replacement medication, sebelipase alfa, showed a reduction in multiple disease-related symptoms in children and adults with lysosomal acid lipase deficiency, an inherited enzyme deficiency that can result in scarring of the liver and high cholesterol.
Fixing Holes in the Heart Without Invasive Surgery
UV-light enabled catheter is a medical device which represents a major shift in how cardiac defects are repaired.
Atriva Therapeutics GmbH Develops Innovative Flu Drug
Highly effective against seasonal and pandemic influenza.
Study Removes Cancer Doubt for Multiple Sclerosis Drug
Researchers from Queen Mary University of London are calling on the medical community to reconsider developing a known drug to treat people with relapsing Multiple sclerosis after new evidence shows it does not increase the risk of cancer as previously thought.
Antibody Treatment Efficacious in Psoriasis
An experimental, biologic treatment, brodalumab, achieved 100 percent reduction in psoriasis symptoms in twice as many patients as a second, commonly used treatment, according to the results of a multicenter clinical trial led by Mount Sinai researchers.
Scientists Test New Gene Therapy for Vision Loss from a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
HIV Patients Should Be Included in Early Clinical Trials of Anti-TB Drugs
Tuberculosis is the number one cause of death in HIV-infected patients in Africa and a leading cause of death in this population worldwide.
Multi-Gene Test Enables Some Breast Cancer Patients to Safely Avoid Chemotherapy
A major study is providing the best evidence to date that a 21-gene test done on the tumor can identify breast cancer patients who can safely avoid chemotherapy.
Low Dose Beta-Blockers As Effective As High Dose After a Heart Attack?
Heart attack patients live as long – or even longer – on one-quarter the suggested dose.
Antidepressants Plus Blood-Thinners Slow Down Brain Cancer
EPFL scientists have found that combining antidepressants with anticoagulants slows down brain tumors (gliomas) in mice.
Scroll Up
Scroll Down

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
2,700+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos