Navigation Links
FDA accepts historical controls for epilepsy monotherapy studies
Date:7/20/2010

New York University researchers revealed that data from previously completed withdrawal to monotherapy studies for antiepileptic drugs (AEDs) provide a valid control for future studies, obviating the need for placebo/pseudo-placebo trials to demonstrate the efficacy of these drugs as monotherapy. Results of this study are now available online in Epilepsia, a journal published by Wiley-Blackwell on behalf of the International League Against Epilepsy.

According to a National Institute of Neurological Disorders and Stroke workshop, monotherapy is the ultimate treatment strategy for newly-diagnosed and many long-term epilepsy patients because of fewer side effects, better compliance, less risk of fetal malformations (teratogencity) and lower cost compared with polytherapy.

However, in the U.S., it is difficult to get monotherapy approval for AEDs because the FDA, in accordance with the International Conference on Harmonization (ICH), requires an internal, interpretable control group in which the test drug shows superiority over the control. New AEDs, while offering improvements in safety and efficacy, rarely demonstrate superiority compared to standard AEDs, leaving placebo or pseudo-placebo as the only acceptable internal controls.

The pseudo-placebo withdrawal to monotherapy study model assigns treatment-resistant patients to receive a study drug or a suboptimal maintenance dose of a safe and effective active drug. Once patients are randomized and standardized to the intended dose, they undergo a withdrawal phase (when background AEDs are removed over a specified time frame) followed by a monotherapy phase. The trial continues until either all phases are completed or patients reach pre-specified endpoints.

Study leader Dr. Jacqueline French explains why this clinical trial model isn't suited for epilepsy patients. "Epilepsy is different from other conditions where placebo may be utilized (such as hypertension), since there is no way to exit a patient at a warning stage, before harm can occur. In a hypertensive patient, one can withdraw a patient on placebo if blood pressure increases, before it gets dangerously high. But with an epilepsy patient, the escape criteria consist of an increase or worsening of seizures, which by itself can be considered an adverse outcome."

The study authors proposed that a historical control, based on an evaluation of prior pseudo-placebo withdrawal to monotherapy studies, would provide a valid alternative to an actual control group. The team analyzed 8 separate studies of similar design and escape criteria, with randomized patients of common demographic characteristics. The primary endpoint was the same for all trials: percent of patients exiting the trial due to seizure worsening. All 8 studies had consistent outcomes, with the percentages of patients exiting their respective trials ranging from 74.9%-95.9%.

Dr. French concludes, "These trials would appear to meet the criteria set forth by ICH for use of historical control. Therefore, this group of trials might reasonably be used as historical controls for future trials of withdrawal to monotherapy using a similar design in a similar population."

The historical control design allows all patients to receive a promising AED at an effective dose, making the study more attractive to patients and to physicians. Dr. Emilio Perucca agreed with these findings, stating in this month's Epilepsia Commentary, "The New York University team should be commended for their scholarly workin setting the stage for a new conversion-to-monotherapy design in which patients are no longer required to receive suboptimal, and therefore, potentially hazardous, treatments."

Based upon this French et al. study, the FDA has accepted the concept of historical controls in this setting, a major milestone in AED development. Several trials utilizing this design planned for regulatory submission have begun.


'/>"/>

Contact: Dawn Peters
healthnews@wiley.com
781-388-8408
Wiley-Blackwell
Source:Eurekalert

Related medicine news :

1. Fired Wal-Mart Employee Accepts Full Scholarship to The Medical Marijuana Academy
2. Hope Shoppe Inc. Accepts Submissions for Seasons of Hope and Donates Proceeds to Non-Profits
3. IHRSA Expresses Its Ardent Support of America's First-Ever National Physical Activity Plan and Accepts Role as Co-Chair of Implementation Sub-Committee
4. Scripps Research scientists uncover previously unknown natural mechanism that controls cocaine use
5. TPG Capital Selects MetricStream GRC Platform to Boost its Internal Controls and Compliance
6. Study finds key protein controls T-cell proliferation
7. PCMA: Federal Enrollees Don't Want Congress to Reduce Pharmacy Choices, Impose Price Controls in FEHBP
8. FDA Tightens Controls on Anemia Drugs
9. Study confirms favorable long-term prognosis of epilepsy
10. Children With Epilepsy Feel on Par With Healthy Siblings
11. Altered brain development found in children with newly diagnosed epilepsy
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/18/2017)... (PRWEB) , ... February 18, 2017 , ... ... today provides the latest information and contact points to easily connect elderly veterans ... care, assisted living, and elder-care funding. It also conveys material on this year's ...
(Date:2/17/2017)... ... February 17, 2017 , ... While EHR data ... has introduced an innovative workstation designed to reduce nursing fatigue while enhancing productivity. ... EHR Workstation offers a lightweight, highly mobile, multi-functional alternative to the limitations of ...
(Date:2/17/2017)... ... February 17, 2017 , ... Wells Pharmacy Network offers physicians ... controlled and non-controlled substances plus the ability to manage orders on their desktop ... now accept electronic prescriptions, according to the Office of the National Coordinator of ...
(Date:2/17/2017)... (PRWEB) , ... February 17, ... ... Device Approval and Reimbursement , **An FDAnews Webinar**, Feb. 22, 2017 — ... are the critical reimbursement questions manufacturers should be asking before selecting an ...
(Date:2/17/2017)... , ... February 17, 2017 , ... ... to Prevent a Warning Letter, **An FDAnews Webinar**, Feb. 23, 2017 — 1:30 ... manufacturers distinguish between corrective action (CA) and preventive action (PA)? , The methods ...
Breaking Medicine News(10 mins):
(Date:2/20/2017)... YORK , Feb. 20, 2017  This report analyzes the ... Million. The report provides separate comprehensive analytics for the US, ... Europe , Asia-Pacific , ... Read the full report: http://www.reportlinker.com/p04707127-summary/view-report.html ... period 2015 through 2022. Also, a six-year historic analysis is ...
(Date:2/20/2017)... 20, 2017  National Decision Support Company (NDSC) ... company,s CareSelect Imaging platform within the full range ... the technical foundation for MEDITECH sites, through a ... Clinical Decision Support Mechanism through the MEDITECH EHR. ... and support the integration of NDSC,s mechanism, which ...
(Date:2/20/2017)... Feb. 20, 2017   Orion Health ™ ... Amadeus precision medicine platform to the Amazon Web ... over 110 million patient records globally. "We ... big data solutions built on modern, scalable technology," said ... Life Sciences. "The AWS Cloud gives healthcare companies a ...
Breaking Medicine Technology: