Name of Guidance:
Status of Guidance:
Final
Date of Guidance:
December 2008
Name of Organizations Releasing the Guidance:
U.S. Department of Health and Human Services (HHS)
U.S. Food and Drug Administration (FDA)
Centers for Drug Evaluation and Research (CDER):
Target Audience:
Sponsors of clinical trials for drugs and therapeutic biologics to treat type 2 diabetes mellitus
Guidance Laws and Regulations Referenced Guidance:
Draft guidance: Diabetes Mellitus Drugs and Therapeutic Biologics for Treatment and Prevention, March 2008: Guidance providing recommendations for sponsors for the design and conduct of phase 2 and 3 clinical trials for evaluating new drugs and biologics to treat type 2 diabetes mellitus
Definitions:
BLA: Biologic Licensing Application. An application submitted to FDA for approval of interstate marketing of a new device.
Blinded: Here, a blinded assessment means the person or persons doing the assessment have no information about the subject or treatment.
Cardiovascular endpoint: an event that can be used as a measure of cardiovascular risk, eg, myocardiatl infarction (heart attack), stroke, or hospitalization for cardiovascular procedures
NDA: New Drug Application. An application submitted to FDA for approval of interstate marketing of a new drug.
Sponsor: A company or an institution that finances a clinical trial.
Background:
Diabetes mellitus is a chronic disease of epidemic proportions causing a significant worldwide financial burden. Because of its importance in the world, many therapies are being used and developed. The disease is caused by defective insulin secretion by the pancreas, resistance to insulin, or both. This leads to abnormal levels of sugar in the blood (high or low blood glucose). Type 1 and 2 diabetes are heritable; type 1 is more severe and insulin treatment is indicated, whereas type 2 can be controlled without insulin. Patients with type 2 diabetes represent an approprieate group in which new treatments for diabetes can be tested, and in whom long-term cardiovascular risk can be assessed. Cardiovascular events that may be used as endpoints for risk assessment include death, myocardial infarction, stroke, or hospitalization for cardiovascular procedures.
Summary:
The present guidance is a final guidance issued after a draft guidance of March 2008 which gave recommendations for developing drugs and biologics for treatment of diabetes mellitus. At a meeting in July 2008, the Endocrinologic and Metabolic Drugs Advisory Committee of the FDA decided that assessment of cardiovascular risk should be addressed in a final guidance to be implemented immediately. This final guidance was issued in December 2008. Another final guidance will be issued separately addressing currently marketed drugs and biologics.
Rationale:
Because diabetes mellitus is associated with abnormal lipid metabolism, cardiovascular risk is elevated in these patients. The FDA recommends that new drugs and biologics in development should be assessed to avoid excessive cardiovascular risk in patients with diabetes mellitus.
Resulting Recommendations:
1) For studies in the planning stage:
· Sponsors of phase 2 and 3 clinical trials should appoint an independent committee to define and assess cardiovascular endpoints in a blinded manner.
· Sponsors should design phase 2 and 3 clinical studies so that meta-analyses can be performed at completion of the study, taking into account several study design characteristics. Patients at higher risk of cardiovascular events should be included in the studies (eg, patients who are elderly, with advanced disease, or with renal impairment). Longer studies may be required to assess long-term cardiovascular risk (ie, 2 years compared to the usual 3 to 6 months).
2) For completed studies before submission to FDA for an NDA or BLA:
· Meta-analyses should be performed comparing treated patients with control groups to demonstrate absence of excessive cardiovascular risk. If the analysis is inconclusive, 1 or more large clinical trials for safety may be required to satisfy statistical requirements.
· Sponsors should show results of meta-analyses using graphical and tabular displays of data that can be verified.
Impact:
Drugs being developed for treatment of type 2 diabetes mellitus will be evaluated for cardiovascular safety before being submitted to FDA for NDAs and BLAs. Clinical trials will be longer (to evaluate long-term safety) and more costly. Patients with the disease will be protected from excessive cardiovascular risk caused by new drugs or biologi
No comments:
Post a Comment