Drug-induced blood pressure increase - recommendations for assessment in clinical and non-clinical studies.
Changes in blood pressure (BP) are now proactively examined throughout the drug development process as an integral aspect of safety monitoring. This is because hypertension is a very strong risk factor for cardiovascular events and drug-induced increases in BP have attracted increased regulatory attention. However, there is currently no guidance from regulatory agencies on the minimum BP data required for submissions, and there are no specific criteria for what constitutes a safety signal for increased BP in non clinical studies. Areas covered: Evaluation of BP increases through the drug discovery and development process. Expert opinion: Research into the effects of drugs should begin before clinical development is initiated and continue throughout the clinical trial program. Non clinical studies should inform a benefit-risk analysis that will aid decision-making of whether to enter the drug into Phase I development. The degree of acceptable risk will vary according to the therapy area, treatment indication and intended population for the new drug, and the approach to BP assessment and risk mitigation should be tailored accordingly. However, BP monitoring should always be included in clinical trials, and data collected from multiple studies, to convincingly prove or refute a suspicion of BP effects.
a Patient Safety , Global Medicines Development, AstraZeneca R&D , Gothenburg , Sweden.
Christer
C
Gottfridsson
b CVMD Global Medicines Development , AstraZeneca R&D , Gothenburg , Sweden.
Seva
S
Panfilov
c ECG Centre, Global Medicines Development , AstraZeneca R&D , Gothenburg , Sweden.
Ahmad
A
Ebrahimi
d Regulatory Policy, Global Medicines Development , AstraZeneca R&D , Gaithersburg , MD , USA.
Emery
E
Gigger
e Drug Safety & Metabolism , AstraZeneca R&D , Cambridge , UK.
Chris
C
Pollard
f Biologics Safety Assessment, MedImmune , Cambridge , UK.
Simon
S
Henderson
g Clinical CVMD, Biologics, MedImmune , Cambridge , UK.
Philip
P
Ambery
h CVMD Global Medicines Development , AstraZeneca R&D , Gaithersburg , MD , USA.
Joel S
JS
Raichlen
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D002986:Clinical Trials as Topic / Q000379:methods; D015195:Drug Design; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000175:diagnosis / Q000517:prevention & control; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D012308:Risk Management / Q000379:methods
Blood pressure; cardiovascular outcomes; clinical development; drug development; drug evaluation; non-clinical development