Successful regulatory agency interaction - A nonclinical regulatory strategist's perspective.

Regulatory agency interaction occurs from before a candidate drug enters clinical development and all the way to marketing approval and beyond. This paper presents ways to enable successful interaction by avoiding issues, with an emphasis on nonclinical testing aspects. Strategic thinking as to whether an early regulatory agency meeting should occur is discussed and if yes, how to make it a success by generating relevant questions with proper preparation including a robust Briefing Document. Examples of unfavourable regulatory agency feedback during meetings is given which may have been avoided. Similarly, ways for successful regulatory submission in the form of a Clinical Trials Application (CTA) in Europe or an Investigational New Drug (IND) application in the US are considered with examples of comments that can be received from regulatory agencies. At marketing application stage with submission of a Marketing Authorisation Application (MAA) in Europe and a New Drug Application (NDA) or a Biologic License Application (BLA) in the US, a key document is the Nonclinical Overview and suggested content and potential deficiencies are presented to allow avoidance of adverse regulatory agency responses and time delay. Successful regulatory agency interaction involves robust scientific thinking, proper planning and well-written documentation.

MIHARI project, a preceding study of MID-NET, adverse event detection database of Ministry Health of Japan-Validation study of the signal detection of adverse events of drugs using export data from EMR and medical claim data.

We studied the effectiveness of the direct data collection from electronic medical records (EMR) when it is used for monitoring adverse drug events and also detection of already known adverse events. In this study, medical claim data and SS-MIX2 standardized storage data were used to identify four diseases (diabetes, dyslipidemia, hyperthyroidism, and acute renal failure) and the validity of the outcome definitions was evaluated by calculating positive predictive values (PPV). The maximum positive predictive value (PPV) for diabetes based on medical claim data was 40.7% and that based on prescription data from SS-MIX2 Standardized Storage was 44.7%. The PPV for dyslipidemia was 50% or higher under either of the conditions. The PPV for hyperthyroidism based on disease name data alone was 20-30%, but exceeded 60% when prescription data was included in the evaluation. Acute renal failure was evaluated using information from medical records in addition to the data. The PPV for acute renal failure based on the data of disease names and laboratory examination results was slightly higher at 53.7% and increased to 80-90% when patients who previously had a high serum creatinine (Cre) level were excluded. When defining a disease, it is important to include the condition specific to the disease; furthermore, it is very useful if laboratory examination results are also included. Therefore, the inclusion of laboratory examination results in the definitions, as in the present study, was considered very useful for the analysis of multi-center SS-MIX2 standardized storage data.

Intimate partner violence is a barrier to antiretroviral therapy adherence among HIV-positive women: Evidence from government facilities in Kenya.

INTRODUCTION: Intimate Partner Violence (IPV) is linked to low engagement with HIV management services and adverse clinical outcomes, including poor ART adherence. In sub-Saharan Africa, studies on pregnant/postpartum women and transactional sex workers have produced divergent evidence regarding IPV's association with poor ART adherence. We investigate this association among a broad group of women. METHODS: We sampled 408 HIV-positive women receiving free ART from different types of HIV clinics at government health facilities, assessing for IPV exposure by a current partner, ART adherence rate, and other factors that affect ART adherence (e.g. education, disclosure). ART adherence rates were measured using the Visual Analogue Scale (VAS); responses were dichotomised at a ≥95% cut-off. Multiple logistic regression models assessed the association between the independent variables and ART adherence. RESULTS: The participants' mean age was 38.6 (range: 18-69 years). The majority had ever attended school (94%, n = 382), were in monogamous marriages (70%, n = 282), and had disclosed status to partners (94%, n = 380). Overall, 60% (n = 242) reported optimal ART adherence (≥ 95%) in the previous 30 days. The prevalence of IPV by the current partner was 76% (CI95 = 72-80%). Experiencing physical IPV (AOR 0.57, CI95: 0.34-0.94, p = .028), sexual IPV (AOR 0.50, CI95: 0.31-0.82, p = .005), or controlling behaviour (AOR 0.56, CI95: 0.34-0.94, p = .027) reduced the odds of achieving optimal adherence, while a higher education level and having an HIV-positive partner increased the odds. CONCLUSION: IPV is common and is associated with suboptimal ART adherence rates among a broad group of HIV-positive women. ART programs could consider incorporating basic IPV interventions into regular clinic services to identify, monitor and support exposed women, as they might be at risk of poor ART adherence. Still, there is need for more research on how IPV affects ART adherence.

A tribute to the foot soldiers: European health agencies in the fight against antimicrobial resistance.

The prevention of antimicrobial resistance (AMR) has been a flagship of the EU's health policy since the early 2000s, leading the European Commission to mandate three European agencies to cooperate in the fight against AMR: EMA (the European Medicines Agency), ECDC (European Centre for Disease Prevention and Control) and EFSA (the European Food Safety Agency). This article is at the intersection of EU health policy and the burgeoning scholarship on bureaucratic reputation. Little is known on the role played by reputational incentives on inter-agency cooperation. This empirical work supports the claim that cooperation creates incentives for agencies to protect their reputational uniqueness vis-à-vis each other. However, rather than threatening their cooperation, it amounts to a process of sense-making of their respective roles in the integrated fight against AMR. Evidence is generated through the agencies' textual sources, as well as in-depth interviews and analysed through a narrative analysis. From the early days of inter-agency cooperation, to recent legislative work, this paper offers in-depth insights on the EU's governance against AMR.

Informe de Rotación Electiva

El presente informe tiene como propósito dar cuenta del trabajo realizado y los aprendizajes alcanzados durante el desarrollo de la rotación de elección libre. La misma ha sido llevada a cabo entre el 16 de marzo y el 21 de abril de 2020 en el Centro de Investigación en Nutrición y Salud (CINyS) perteneciente al Instituto Nacional de Salud Pública (INSP) de México. En las siguientes páginas se presentará la sede de rotación y la fundamentación relativa a la relevancia de la elección de la misma. Asimismo, se explicitarán los objetivos propuestos y las actividades desarrolladas a lo largo del mencionado período. Finalmente, se presentará una reflexión a partir de los aprendizajes logrados y los aportes que se intentó realizar tanto desde el campo de la nutrición como desde la Educación y Promoción de la Salud. (AU)

[The role of Public Health as a key to the success of the neonatal screening program in the Basque Country.] / El papel de la Salud Publica como clave del éxito del Programa de Cribado Neonatal en el País Vasco.

Neonatal Screening Programs (PCN) have widely demonstrated their benefits since Dr. Guthrie published his developments on Phenylketonuria (PKU) in 1961. This paper describes how a simple and effective organization, which incorporates all the fundamental actors under the responsibility of the Public Health Directorate (DSP), has managed to ensure that the PCN of the Basque Country meets all the objectives required for a population screening. The acceptance by Basque society of the PCN allowed it to exceed 95% coverage in its second year of operation. Likewise, the limited negative social impact of PCN is evidenced by its low number of false positives and incorrect samples. Excellent response times allow every newborn with a positive result to have an early diagnosis and optimal initiation of treatment. There are two relevant experiences that support the importance of the effective exercise of the responsibility of the DSP. Congenital adrenal hyperplasia (CAH) was incorporated into the PCN in 1991 meeting all technical and clinical criteria. At the request of the experts, the DSP ordered in 1993 to cease this activity showing that it did not provide the expected benefits. The problems of organically integrating the PCN into the healthcare system were also experienced. The need to compete for resources put public health activities, including the PCN, at risk and led to their return to direct dependence on the DSP. The availability of this structure, in addition to facilitating the incorporation of other screenings, allows facing the future challenges.

Los Programas de Cribado Neonatal (PCN) han demostrado ampliamente sus beneficios desde que en 1961 el Dr. Guthrie publicó sus trabajos sobre Fenilcetonuria (PKU). En este trabajo se describe cómo una organización sencilla y eficaz, que incorpora a todos los actores fundamentales bajo la responsabilidad de la Dirección de Salud Pública (DSP), ha conseguido que el PCN del País Vasco cumpla con todos los objetivos exigibles a un cribado poblacional. La aceptación por la sociedad vasca del PCN permitió superar el 95% de cobertura en su segundo año de funcionamiento. Asimismo, el limitado impacto social negativo del PCN se evidencia por su reducido número de falsos positivos y de muestras incorrectas. Los excelentes tiempos de respuesta permiten que todo recién nacido con resultado positivo disponga de un diagnóstico temprano y de un inicio óptimo del tratamiento. Hay dos experiencias relevantes que avalan la importancia del ejercicio eficaz de la responsabilidad de la DSP. La hiperplasia adrenal congénita (HAC) se incorporó en 1991 al PCN, cumpliendo con todos los criterios técnicos y clínicos. A petición de los expertos, la DSP ordenó en 1993 cesar esta actividad al evidenciar que no aportaba los beneficios esperados. También se experimentaron los problemas de integrar orgánicamente el PCN en el sistema asistencial. La necesidad de competir por los recursos puso en riesgo las actividades de Salud Pública, incluyendo el PCN, lo que provocó su retorno a la dependencia directa de la DSP. La disponibilidad de esta estructura, además de facilitar la incorporación de otros cribados, permite afrontar los retos del futuro.

Seventy years' achievements of international cooperation by the National Institute of Parasitic Diseases at the Chinese Center for Disease Control and Prevention.

BACKGROUND: With the promotion of national control programs on parasitic and tropical diseases in China, the National Institute of Parasitic Diseases (NIPD), Chinese Center for Disease Control and Prevention has gained significant experience in the global health arena through international cooperation over the last seven decades allowing a multilateral impact in the elimination of major endemic diseases. METHODS: The achievements of NIPD since 1950 has been analyzed with emphasis on the various stages that started with research and control of the endemic parasitic and other tropical diseases at the national level and progressed via international cooperation into a global presence. RESULTS: The major achievements contributed by NIPD consist of (i) improving technical capability; (ii) promoting control and elimination of parasitic and tropical diseases; (iii) participating in global health governance and cooperation; and (iv) developing a cooperation model for technical assistance and global public health development. It is expected that NIPD's experience of international cooperation will be essential for the dissemination of China's successful experience in global health governance, emergency response and development, with focus on malaria and neglected tropical diseases such as schistosomiasis, soil-borne and food-borne helminthiases and echinococcosis. CONCLUSIONS: NIPD's new tasks will not only continue to promote national control of endemic parasitic infections and disease elimination programs in China, but also play a leading role in global health and disease elimination programs in the future.

The Institute for Health Protection and its role in tackling COVID-19.

Emeritus Professor Alan Glasper, from the University of Southampton, discusses the role of the newly created Institute for Health Protection, which has subsumed the work of Public Health England and other organisations.

Evaluation of performance-enhancing drugs seized by Israeli enforcement agencies 2012-2017: implications for policy and regulatory change.

BACKGROUND: Illicit performance-enhancing substances are used mostly by athletes to enhance performance in sports, and by bodybuilders to gain muscle and body mass. Among performance-enhancing substances, the most common and known substances are anabolic-androgenic steroids, which are associated with a range of short and long-term adverse medical and psychiatric effects. While the sale and distribution of performance-enhancing substances are considered criminal offenses per the Israeli local pharmacy ordinance, the use and personal possession of these substances are not. Presently, the Division of Enforcement and Inspection of the Israel Ministry of Health cooperates with police and customs agents in performance-enhancing substance-related enforcement activities, which chiefly include seizures carried out at suspicious sites. Moreover, the Division of Enforcement and Inspection provides professional guidance, lab analysis services, and expert opinions on the toxicological and pharmaceutical nature of products seized. This paper presents a contemporary sub-analysis of registered seizures of performance-enhancing substances carried-out by Israel enforcement agencies. The main aim of this analysis is to characterize current patterns of performance-enhancing substances, thus providing the possibility of better assessment of current enforcement and health policy. METHODS: A sub-analysis of 712 seizures of performance-enhancing substances seized by Israeli enforcement authorities during a six-year period ranging from January 2012 to December 2017. RESULTS: This study demonstrates that Israel faces a challenge regarding the importation and distribution of illicit performance-enhancing substances. The most common substances seized were anabolic androgenic steroids (N = 539). Most seizures were carried out in the central mail processing sites, (38.4%), followed by seizures in private premises such as homes and warehouses (29.6%). Significant differences were found between anabolic-androgenic steroids and other substances, relating to place and year of seizure. Among seizures with known sources (N = 355), the most frequent geographic region given as the source of substances was Eastern Europe (47.6%), followed by East Asia (24.8%), West Asia (19.4%), and Western Europe (5.9%). Bulgaria was the country with the highest frequency of seizures (N = 71) followed by Jordan (N = 45), Thailand (N = 37) and Moldova (N = 36). Significant regional differences were found based on the variables of gender, place of seizure, and type of substance. The most frequent month of seizures was August (N = 129), followed by July (N = 119), and June (N = 118). CONCLUSIONS: While data analysis focused on the supply side of the performance-enhancing substances market, the high number of seizures of performance-enhancing substances in Israel represents evidence of the existence of a high demand and a large consumer base for these products. Consequently, there is a need for developing further enforcement, treatment, and prevention policies that do not currently exist in Israel. Policymakers should consider prioritizing law enforcement action and incentivizing intelligence sharing to monitor suspected shipment sources and specific points of entry. Additionally, the results demonstrate that there is a need in reforming the penal law to discourage the use of performance-enhancing substances. Similar measures have already been applied in countries like Spain, Italy, and Belgium. Furthermore, policy-makers should consider enhancing health ministry agencies with a higher enforcement capacity by giving them further investigative and inquiry authority. Due to the troubling magnitude of the phenomenon, policymakers should also prioritize educational and prevention strategies.