Benefit Risk Management Research Articles

Preparing of Point-of-Care Reagents for Risk Assessment in the Elderly at Home by a Home-Visit Nurse and Verification of Their Analytical Accuracy.

With the rising number of older adults residing at home, there is a growing need for risk assessment and patient management in home nursing. This study aims to develop point-of-care test (POCT) reagents that can aid in risk assessment and home care, especially in settings with limited resources. Our focus was on creating a C-reactive protein (CRP) POCT, which can accurately diagnose clinically significant judgment values in home nursing. Additionally, we assessed the utility of the HemoCue WBC DIFF system in providing differential counts of white blood cells (WBC). These performances were compared with a laboratory test using blood samples from patients with pneumonia. The CRP POCT showed a comparable result to that of a laboratory method, with an average kappa index of 0.883. The leukocyte count showed good agreement with the reference method. While the correlation coefficients for both neutrophil and lymphocyte counts were deemed acceptable, it was observed that the measured values tended to be smaller in cases where the cell count was higher. This proportional error indicates a weak correlation with the neutrophil-to-lymphocyte ratio. CRP POCT and WBC counts provided reliable and accurate judgments. These tools may benefit risk management for older adults at home, patients with dementia who cannot communicate, and those living in depopulated areas.

Understanding violent extremism: Risk and protective factors in a jihadi male detainee population in the Netherlands

In recent years, the number of detainees confined for terrorism-related offenses has increased worldwide and across Europe. To understand the factors related to terrorism and its underlying motives, this study provides insights into violent extremism by assessing risk- and protective factors based on the Violent Extremism Risk Assessment-2R (VERA-2R) in 121 male jihadist residents in Dutch terrorism wings. Retrospective analyses of primary source data showed that one-third of the target group is strongly connected to ideologies justifying violence. The social context of the study sample was also related to violent extremism, whereas support from family members emerged as the most often observed protective factor. The current findings suggest that including meaningful risk and protective factors of detained male jihadists may benefit risk management strategies in prevention, intervention, and policy practices related to violent extremism.

Systematising Pharmacovigilance Engagement of Patients, Healthcare Professionals and Regulators: A Practical Decision Guide Derived from the International Risk Governance Framework for Engagement Events and Discourse.

IntroductionInput from patients and healthcare professionals to regulatory assessments is essential for benefit–risk management of medicines. How to best obtain input in different risk scenarios is uncertain.ObjectivesThe objective of this study was to investigate whether the International Risk Governance Council (IRGC) Framework is applicable to pharmacovigilance and can guide selecting engagement mechanisms for optimising stakeholder input.MethodsFor proof-of-concept, classify ‘iconic’ cases of pharmacovigilance engagement at the European Medicines Agency (EMA) by IRGC risk scenario types and compare the engagement that happened with the engagement discourse recommended by the IRGC Framework for different risk scenarios. If the concept is proven, derive proposals for strengthening engagement.ResultsSix iconic cases were classified by risk scenario type at the respective time points when deciding on engagement: venous thromboembolism with combined hormonal contraceptives (complex risk); lipodystrophy with highly active antiretroviral therapy medicines, carcinogenicity with contaminated nelfinavir products (uncertain risks); teratogenicity with thalidomide, progressive multifocal leukoencephalopathy with natalizumab, teratogenicity and developmental disorders with valproate (ambiguous risks). The comparison of the engagement events with IRGC recommendations showed correspondence between the scope/outcomes of the events and the features of the recommended discourse.ConclusionsThe IRGC Framework appears applicable to pharmacovigilance. Proposals derived from the IRGC recommendations may be valuable for guiding regulators when selecting mechanisms for engagement with patients and healthcare professionals in given risk scenarios. The proposed decision guide aims at ensuring systematic and consistent engagement across regulatory assessments and providing for the most purposeful discourse, to effectively obtain real-world input for regulatory risk assessment, evaluation of risk minimisation measures and decision making.

Drug safety in multiple sclerosis: From reporting to signal detection and benefit-risk management

Pharmacovigilance (PV) rules emerged in the late 60s-early 70s. Since that time, the World Health Organization Center for International Drug Monitoring carries out the corresponding tasks. Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system that generally starts in young adults between 20 and 40 years of age. Over the last 25 years, MS patients have benefited from the development of a plethora of disease modifying drugs (DMD). These changes in the therapeutic armamentarium have been associated with some serious adverse reactions challenging health authorities and neurologists involved in treatment and care for MS patients. The present review aims to describe, for MS DMDs, how adverse drug reactions are reported during clinical trials and the post-marketing period and how important signal detection and benefit-risk management have been in this disease until now. Several examples are reported to illustrate the different steps of PV processes. Improvement of the PV system procedures has led to significant progress in the detection of signals, allowing better assessment of the benefit-risk balance and the implementation of risk management plans for MS treatments. The involvement of neurologists is essential to improve knowledge on the benefit-risk balance of these drugs. In addition, adverse drug reactions reporting by persons with MS should be encouraged.

Risk Management for the 21st Century: Current Status and Future Needs.

Global adoption of risk management principles outlined in the International Conference on Harmonisation (ICH) E2E guideline and the Council for International Organizations of Medical Sciences (CIOMS) Working Group VI guidance introduced greater proactivity and consistency into the practice of pharmacovigilance and benefit–risk management throughout the lifecycle of a drug. However, following the release of these guidelines there have been important advances in the science and practice of risk minimisation itself, especially in terms of how risk minimisation measures (RMMs) are designed, implemented, disseminated and evaluated for effectiveness in real-world healthcare settings. In this article, we describe how the field of design, implementation, dissemination and evaluation of RMMs has advanced in recent years while highlighting current areas of challenge and possible solutions. Where possible we cite global examples to demonstrate how evidence-based approaches have informed the development of RMMs. In this context, while taking into consideration local healthcare system policies and national legislations, we conclude with a call for a global effort to harmonise certain areas that focus on, but are not limited to, standardising certain terms and definitions, consistent application of robust methodologies, and outline of best practices for risk minimisation design, implementation, and dissemination.

Vitamin D and Cardiovascular Disease: An Update

In the clinical setting, administration of high daily or bolus doses of vitamin D is often solely based on 25-hydroxyvitamin D [25(OH)D] testing. This review summarizes the evidence of the effect of vitamin D on cardiovascular disease (CVD). Meta-analyses of randomized controlled trials (RCTs) have demonstrated that CVD risk markers, such as lipid parameters, inflammation markers, blood pressure, and arterial stiffness, are largely unaffected by vitamin D supplementation. Similar results have been obtained regarding CVD events and mortality from (meta)-analyses of RCTs, even in subgroups with 25(OH)D concentrations <50 nmol/l. Likewise, Mendelian randomization studies have indicated that the genetic reduction of the 25(OH)D concentration does not increase CVD risk. Some studies do not exclude the possibility of adverse vitamin D effects, such as elevated plasma calcium concentration and an increased CVD risk at a 25(OH)D concentration >125 nmol/l. Based on a conservative benefit-risk management approach, vitamin D doses beyond the nutritionally recommended amounts of 600 to 800 IE daily currently cannot be advised for the prevention of CVD events.

Adoption of Building Information Modelling in project planning risk management

An efficient and effective risk management required a systematic and proper methodology besides knowledge and experience. However, if the risk management is not discussed from the starting of the project, this duty is notably complicated and no longer efficient. This paper presents the adoption of Building Information Modelling (BIM) in project planning risk management. The objectives is to identify the traditional risk management practices and its function, besides, determine the best function of BIM in risk management and investigating the efficiency of adopting BIM-based risk management during the project planning phase. In order to obtain data, a quantitative approach is adopted in this research. Based on data analysis, the lack of compliance with project requirements and failure to recognise risk and develop responses to opportunity are the risks occurred when traditional risk management is implemented. When using BIM in project planning, it works as the tracking of cost control and cash flow give impact on the project cycle to be completed on time. 5D cost estimation or cash flow modeling benefit risk management in planning, controlling and managing budget and cost reasonably. There were two factors that mostly benefit a BIM-based technology which were formwork plan with integrated fall plan and design for safety model check. By adopting risk management, potential risks linked with a project and acknowledging to those risks can be identified to reduce them to an acceptable extent. This means recognizing potential risks and avoiding threat by reducing their negative effects. The BIM-based risk management can enhance the planning process of construction projects. It benefits the construction players in various aspects. It is important to know the application of BIM-based risk management as it can be a lesson learnt to others to implement BIM and increase the quality of the project.

Benefit Risk Management Plans?

Benefit Risk Management Plans?

Benefit-risk management in the age of personalized healthcare.

The ongoing developments in personalized healthcare are opening new possibilities for the optimization of the benefit-risk profiles of drugs based on the stratification of patients. Beyond this straightforward application of pharmacogenomics to the optimization of benefit-risk profiles, other approaches, such as metabolomics and systems pharmacology, may contribute to an improved use of medicines in a personalized healthcare setting. These will, however, require fundamental adaptations or new developments in various areas and by all stakeholders, including the pharmaceutical and diagnostics industries, regulators, physicians and patients. Ultimately, personalized healthcare should enable patients to take personal decisions on treatment options based on their preferred benefit-risk profiles of therapeutics.

An agenda for UK clinical pharmacology: Development and delivery of clinical pharmacology in regulatory agencies

Medicines regulation is based on a foundation of science, policy and judgement. It operates within several frameworks (scientific, legal and public health), which are interdependent. While safety, quality and efficacy remain the criteria by which medicines are assessed, the benefit-to-harm balance for any medicine or medical device is of paramount importance. While the regulator was hitherto the gatekeeper who allowed a medicine on to the market, payers now require, in addition, assessment of cost and clinical effectiveness before use. As regulatory frameworks develop, several changes will occur, as follows: (i) formal benefit-harm assessment will become an integral part of submission for marketing authorizations; (ii) there will be greater use of surveillance for adverse reactions to new medicines using methods other than voluntary reporting; (iii) risk management plans will become benefit-risk management plans; (iv) life-saving medicines will be approved earlier; and (v) regulation and health technology assessment will take place simultaneously. Clinical pharmacologists will play important roles in these developments.

The role of Indigenous knowledge in environmental health risk management in Yukon, Canada

Objectives. This project aimed to gain better understandings of northern Indigenous risk perception related to food safety and to identify the role that Indigenous knowledge (IK) plays in risk management processes to support more effective and culturally relevant benefit-risk (B-R) management strategies.Study design. The project used an exploratory qualitative case study design to investigate the role and place of IK in the management of environmental contaminants exposure via consumption of traditional foods in Yukon First Nations (YFNs).Methods. Forty-one semi-directive interviews with Traditional Food Knowledge Holders and Health and Environment Decision-makers were conducted. A review and analysis of organizational documents related to past risk management events for the issue was conducted. Thematic content analysis was used to analyze transcripts and documents for key themes related to the research question.Results. There was a recognized need by all participants for better collaboration between scientists and YFN communities. YFNs have been involved in identifying and defining community concerns about past risk issues, setting a local context, and participating in communications strategies. Interviewees stressed the need to commit adequate time for building relationships, physically being in the community, and facilitating open communication. Conducting community-based projects was identified as critical for collaboration and for cooperative learning and management of these issues.Conclusions. The perception of “effective” benefit-risk management is significantly influenced by the efforts made to include local communities in the process. A set of common guiding principles within a process that brings together people and knowledge systems may provide a more effective way forward in cross-cultural, multiple knowledge system contexts for complex benefit-risk issues than a prescriptive rigid framework.

The Annuity Bulk Buy-Out Market. A Discussion Meeting

INTRODUCTIONThis Sessional Meeting takes the form of a panel discussion, asking the question: “Managing defined benefit risk management: is buy-out the future?”The following are subjects for discussion:— What is driving the increased interest in buy-out and other risk transfer solutions?— Will it last?— Who are the players in this market? Is there room for everyone? Is there enough capital?— What impact will current economic conditions have on decisions which trustees make?— What is the role of the Regulator, and how is regulation evolving?— Are products evolving to meet market needs?— What are the implications for actuarial pension consultants of the growing buy-out market?

Radiation doses to normal tissues and organs outside the target volume during radiotherapy

Public Health Codes more and more require that any information relevant to the estimation of the high doses delivered within the target volumes and low doses delivered outside should be recorded. In this context, the availability for each radiotherapy patient of the magnitude of the unavoidable low doses delivered outside the target-volumes becomes an important issue. However, to date, Treatment Planning Systems (TPS) are not designed for this issue. Therefore, we have developed a new version of the ISOgray TPS which can provide, in addition to the doses distributions in the fields, the magnitude of the doses to distant healthy tissues in the course of common radiotherapeutic procedures. Our strategy involves 3 modules: A library of adjustable whole-body patient models in treatment position which allows different patient anatomies to be simulated; A multi-sources beam model, which allows the description of the irradiation field to be extended to the whole body; A dose calculation engine producing the distributions of doses in the fields and in any organ outside. This paper describes the principles of the system and provides data on doses distributions to distant organs for various common radiotherapeutic procedures. At this stage of development, the agreement of measured and calculated doses reaches ±3% in the radiation field and is better than ±15% outside. In the case of a 17 years aged girl treated for Hodgkin's disease using two 6MV opposite photon beams, when a dose of 20 Gy was delivered to the target volume, outside the beam, the dose to the brain was 0.37 Gy (1.85% of the tumor dose), the kidney 0.06 Gy (0.30%) and the ovaries below 0.02 Gy (<0.1%). Although the development of our system is still in progress, these preliminary results are encouraging. Allowing the realization of whole-body dose evaluations for each patient in the course of radiation therapy treatment planning, our approach must provide relevant information required to meet the current requirements of patient radiation protection and radiation therapy benefit-risk management purposes. The systematic evaluation of low doses outside the radiation therapy fields creates new opportunities in quality assurance of radiation therapy and prospective studies of long-term risks of radiation modern radiotherapeutic procedures.

Evaluating the Postmarketing Experience of Risperidone Use During Pregnancy

A significant number of women of childbearing age have schizophrenia or other psychoses. This means that there is a considerable risk of in utero exposure to risperidone due to maternal use. To determine whether in utero exposure to the atypical antipsychotic risperidone is associated with poor pregnancy and fetal/neonatal outcomes. A search of the Benefit Risk Management Worldwide Safety database, using a selection of preferred terms from the Medical Dictionary of Regulatory Activities, was performed to identify all cases of pregnancy or fetal/neonatal outcomes reported in association with risperidone treatment from its first market launch (international birth date, 1 June 1993) to 31 December 2004. The main measures were the patterns and reporting rates of pregnancy (stillbirth and spontaneous and induced abortion) and fetal/neonatal outcomes (congenital abnormalities, perinatal syndromes and withdrawal symptoms) for women administered risperidone during pregnancy. Overall, 713 pregnancies were identified in women who were receiving risperidone. Data were considered prospective in 516 of these, and retrospective in the remaining 197 cases. The majority of the known adverse pregnancy and fetal/neonatal outcomes were retrospectively reported. Of the 68 prospectively reported pregnancies with a known outcome, organ malformations and spontaneous abortions occurred 3.8% and 16.9% (when the 15 induced abortions were excluded from the denominator, as they were predominantly undertaken for nonmedical reasons), respectively, a finding consistent with background rates of the general population. There were 12 retrospectively reported pregnancies involving major organ malformations, the most frequently reported of which affected the heart, brain, lip and/or palate. There were 37 retrospectively reported pregnancies involving perinatal syndromes, of which 21 cases involved behavioural or motor disorders. In particular, there was a cluster of cases reporting tremor, jitteriness, irritability, feeding problems and somnolence, which may represent a withdrawal-emergent syndrome. This comprehensive review of the Benefit Risk Management Worldwide Safety database for case reports of risperidone exposure during pregnancy represents the largest ever published dataset documenting pregnancy outcomes for women taking the atypical antipsychotic risperidone. It indicates that in utero exposure to risperidone does not appear to increase the risk of spontaneous abortions, structural malformations and fetal teratogenic risk above that of the general population. Self-limited extrapyramidal effects in neonates were observed after maternal exposure to risperidone during the third trimester of pregnancy. Risperidone should only be used during pregnancy if the benefits outweigh the potential risks.