Postmarketing Surveillance Studies-An Industry Perspective on Changing Global Requirements and Implications.

PURPOSE: This article describes postmarketing surveillance (PMS) study regulations and expectations of the regulatory agencies in 5 countries. With a focus on postapproval drug safety, there is a continuous need for understanding the benefit-risk profile of an approved drug. In addition to spontaneous adverse-event reporting, regulatory agencies seem to be more reliant on PMS studies. The opportunity to systematically monitor use in special populations, such as elderly patients and those with comorbid conditions, also presents itself during postmarketing use. Regulatory agencies in Japan, the Republic of Korea, and Mexico are requiring such studies as standards or conditions of drug approvals and license renewals. These studies are meant to be observational and noninterventional, over specified time periods. Studies are required specifically for following up treated patients in clinical practice, with the main objective of collecting safety data to further characterize the benefit-risk profile that was established during clinical trials and particularly in the country-specific population. METHODS: We reviewed and compared the published PMS guidelines and requirements in Japan, the Republic of Korea, the People's Republic of China, India, and Mexico. Interpretations of the guidelines and requirements are included and are based on direct interactions with the different regulatory agencies. FINDINGS: We note that the different country PMS guidelines are at varying points in development. While some countries have more comprehensive guidelines, in others, the guidelines are still evolving. The similarities among guidelines include the requirements of the content and format of protocols, periodic reports, and interim reports of PMS studies. The differences in the requirements of PMS studies, such as sample size and study duration, are noticeable. These protocols are to be submitted, together with the respective risk-management plans, for approval by the regulatory authority prior to implementation of the study. IMPLICATIONS: Conventional drug discovery and approval processes are well understood, and there are ample regulatory guidelines and International Conference of Harmonisation-based reference documents for understanding the path of the drug-approval process. Limited information is currently available with regard to the regulations and how PMS studies should be developed and evaluated. Some of the country-specific elements included can inform readers while they prepare to develop and implement PMS study protocols.

Readiness to change problematic drinking assessed in the emergency department as a predictor of change.

OBJECTIVES: The goal of this study was to determine if baseline readiness to change the drinking behavior (pre-contemplation, contemplation, preparation, and action stages) was predictive of change in drinking after unrelated emergency department (ED) visit and screening and interviewing for alcohol problems. METHODS: From August 1998 through December 2000, the Alcohol Use Disorders Identification Test (AUDIT) was administered to all consented ED patients aged 18 to 29 years. A brief motivational interviewing was provided to screen-positive patients (AUDIT score >5 of 40). Outcome at 3-month follow-up was measured as a decrease in the scores within the AUDIT domains of alcohol intake, harm, and dependency. RESULTS: Sixty percent of the screen-positive patients continued to drink at 3 months. Patients became more open to change their drinking behavior. Compared with patients in the pre-contemplation stage, those in the action stage were twice as likely to reduce their alcohol intake (OR, 2.24; 95% CI, 1.06-4.72), nearly 3 times as likely to reduce their alcohol-related harm behavior (OR, 2.80; 95% CI, 1.59-4.91), and almost 4 times more likely to decrease their dependency symptoms (OR, 3.59; 95% CI, 1.97-6.57). Compared with pre-contemplation patients, those in the contemplation stage were nearly twice as likely to reduce their alcohol-related harm (OR, 1.85; 95% CI, 1.02-3.33) and those in the preparation stage were more than twice as likely to reduce their dependency symptoms (OR, 2.20, 95% CI, 1.13-4.27). CONCLUSIONS: Stages of change at baseline appeared to be significant predictors of change in alcohol intake, harm, and dependency symptoms among young adult ED patients.

Systems modeling in support of evidence-based disaster planning for rural areas.

The objective of this communication is to introduce a conceptual framework for a study that applies a rigorous systems approach to rural disaster preparedness and planning. System Dynamics is a well-established computer-based simulation modeling methodology for analyzing complex social systems that are difficult to change and predict. This approach has been applied for decades to a wide variety of issues of healthcare and other types of service capacity and delivery, and more recently, to some issues of disaster planning and mitigation. The study will use the System Dynamics approach to create computer simulation models as "what-if" tools for disaster preparedness planners. We have recently applied the approach to the issue of hospital surge capacity, and have reached some preliminary conclusions--for example, on the question of where in the hospital to place supplementary nursing staff during a severe infectious disease outbreak--some of which we had not expected. Other hospital disaster preparedness issues well suited to System Dynamics analysis include sustaining employee competence and reducing turnover, coordination of medical care and public health resources, and hospital coordination with the wider community to address mass casualties. The approach may also be applied to preparedness issues for agencies other than hospitals, and could help to improve the interactions among all agencies represented in a community's local emergency planning committee. The simulation models will support an evidence-based approach to rural disaster planning, helping to tie empirical data to decision-making. Disaster planners will be able to simulate a wide variety of scenarios, learn responses to each and develop principles or best practices that apply to a broad spectrum of disaster scenarios. These skills and insights would improve public health practice and be of particular use in the promotion of injury and disease prevention programs and practices.

Matched analysis of parent's and children's attitudes and practices towards motor vehicle and bicycle safety: an important information gap.

The purpose of this study was to compare parents' and children's attitudes and habits towards use of bicycle helmets and car seat belts. We hypothesized that parental perception of their children's safety practices did not reflect actual behavior and further, that parental practices, rather than their beliefs about a particular safety practice, have a greater affect on their child's risk-taking behavior. The study population consisted of children in grades four and five and their parents/guardians. Participation in the cross-sectional study was voluntary and confidential anonymous questionnaires were used. In separate and independent surveys, children and parents were questioned in parallel about their knowledge, habits and attitudes toward bicycle helmet use and car safety practices. In the study, 731 students participated with 329 matched child-parent pairs. Ninety-five percent of the children own bicycles and 88% have helmets. Seventy percent of parents report their child always wears a helmet, while only 51% of children report always wearing one (p < 0.05). One-fifth of the children never wear a helmet, whereas parents think only 4% of their children never use one (p < 0.05). Parents report their children wear seat belts 92% of the time while 30% of children report not wearing one. Thirty-eight percent of children ride bicycles with their parents and wear their helmets more often than those who do not ride with their parents (p < 0.05). Parents who always wear a seat belt are more likely to have children who sit in the back seat and wear a seat belt (p < 0.05). Parents' perceptions of their children's safety practices may not be accurate and their actions do affect their children's. Injury prevention programs that target both parents and children may have a greater impact on reducing risk-taking behaviors than working with each group in isolation.