Submitted by Jeffrey Heilbraun on October 8, 2013
This week, I will be hosting a webinar focused on considerations and best practices for Blood Pressure (BP) monitoring as part of the cardiac safety assessment for compounds in development. The evaluation of BP responses to drugs being developed for non-cardiovascular indications is garnering increased public awareness and regulatory focus, evidenced by formal scientific discussions at prominent meetings and recent publications by the Cardiac Safety Research Consortium (CSRC) on this topic.
When designing a study aimed at measuring the “off-target” BP effect of a compound, there are a number of factors to keep in mind. Here are 3 key considerations for accurately defining the off-target BP effect and maximizing the potential of your blood pressure cardiac safety study.
- Do changes in blood pressure relate to compound concentration?
It is important to determine whether an off-target BP signal is associated with increasing drug concentrations or if it is independent of drug concentration. Determining whether the observed change in BP (as well as other safety and efficacy measures) shows dose dependency with your compound provides valuable clinical information, including delineating a specific concentration threshold that is associated with changes in BP. Evaluating the concentration effect on BP signal within a SAD or MAD study in the early phase development of a compound can be beneficial prior to moving into a phase II, patient-based population
- Blood pressure signals for short and long term exposure to a therapeutic compound.
Establishing a comprehensive BP profile of a compound provides valuable information from a clinical management and regulatory perspective. When evaluating a study compound, it is important to determine if the BP response reaches a plateau or continues to increase as a function of extended exposure. Furthermore, from a safety perspective it may be important to understand what occurs to the BP upon cessation of drug treatment (i.e. does the BP return to baseline or to a clinically appropriate threshold?).Data regarding the fluctuations of BP signals is important as it informs the sponsor whether changes in BP are resolvable or if additional intervention (in the form of secondary medications) is required to safely use the compound. This can become an important consideration based on the therapeutic indication and whether or not the medication is taken on a long term basis, short term basis or intermittently when disease symptoms are present.
- What are the available options for evaluating the blood pressure changes?
When it comes to monitoring BP, there are several options for the sponsor to consider based on a number of parameters including clinical study phase, patient population, therapeutic indication and an understanding of BP response profiles obtained during early compound development. Advances in BP technology enable efficient capture of BP measurements in both the clinic and office setting as well as directly from a patient’s home. Pilot studies of BP measurements are often used as a guide for selecting an approach.Common BP measurement and monitoring options include:
- 24-hour Ambulatory Blood Pressure Monitoring. ABPM is a key diagnostic technology, providing surrogate endpoint data describing BP changes over 24 hour time periods. Constant monitoring enables evaluation across circadian rhythms, providing a more comprehensive analysis of BP changes. ABPM data are now included in a number of regulatory submissions for novel drugs and are increasingly considered for determining new drug safety during regulatory review.
- Automated office blood pressure monitoring. The benefits of using automated BP monitoring include calibration and standardization of equipment across study sites and removal of variability resulting from human/auscultatory bias.
- Remote home blood pressure monitoring. Telemonitoring provides a means of electronically transferring study participant, self-monitored BP data to a central repository, reducing the number of patient visits and increasing patient compliance for a study. This methodology is valuable for providing real time visibility into blood pressure trends during the conduct of the study.
Be sure to join me on Oct 10th to further explore best practices for BP monitoring in clinical trials and gain perspective from a pharmaceutical sponsor who has been directly involved in addressing and navigating approaches to defining an off-target BP signal for a developing compound.
Link to original press release: http://www.bioclinica.com/blog/blood-pressure-endpoints-clinical-trials-are-you-monitoring