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.

Governance of health research funding institutions: an integrated conceptual framework and actionable functions of governance.

BACKGROUND: Health research has scientific, social and political impacts. To achieve such impacts, several institutions need to participate; however, health research funding institutions are seldom nominated in the literature as essential players. The attention they have received has so far focused mainly on their role in knowledge translation, informing policy-making and the need to organise health research systems. In this article, we will focus solely on the governance of national health research funding institutions. Our objectives are to identify the main functions of governance for such institutions and actionable governance functions. This research should be useful in several ways, including in highlighting, tracking and measuring the governance trends in a given funding institution, and to forestall low-level governance. METHODS: First, we reviewed existing frameworks in the grey literature, selecting seven relevant documents. Second, we developed an integrated framework for health research funding institution governance and management. Third, we extracted actionable information for governance by selecting a mix of North American, European and Asian institutions that had documentation available in English (e.g. annual report, legal status, strategy). RESULTS: The framework contains 13 functions - 5 dedicated to governance (intelligence acquisition, resourcing and instrumentation, relationships management, accountability and performance, and strategy formulation), 3 dedicated to management (priority-setting, financing and knowledge transfer), and 5 dedicated to transversal logics that apply to both governance and management (ethics, transparency, capacity reinforcement, monitoring and evaluation, and public engagement). CONCLUSIONS: Herein, we provide a conceptual contribution for scholars in the field of governance and health research as well as a practical contribution, with actionable functions for high-level managers in charge of the governance of health research funding institutions.

Exploring the evolution of engagement between academic public health researchers and decision-makers: from initiation to dissolution.

CONTEXT: Relationships between researchers and decision-makers have demonstrated positive potential to influence research, policy and practice. Over time, interest in better understanding the relationships between the two parties has grown as demonstrated by a plethora of studies globally. However, what remains elusive is the evolution of these vital relationships and what can be learned from them with respect to advancing evidence-informed decision-making. We therefore explored the nuances around the initiation, maintenance and dissolution of academic-government relationships. METHODS: We conducted in-depth interviews with 52 faculty at one school of public health and 24 government decision-makers at city, state, federal and global levels. Interviews were transcribed and coded deductively and inductively using Atlas.Ti. Responses across codes and respondents were extracted into an Excel matrix and compared in order to identify key themes. FINDINGS: Eight key drivers to engagement were identified, namely (1) decision-maker research needs, (2) learning, (3) access to resources, (4) student opportunities, (5) capacity strengthening, (6) strategic positioning, (7) institutional conditionalities, and (8) funder conditionalities. There were several elements that enabled initiation of relationships, including the role of faculty members in the decision-making process, individual attributes and reputation, institutional reputation, social capital, and the role of funders. Maintenance of partnerships was dependent on factors such as synergistic collaboration (i.e. both benefit), mutual trust, contractual issues and funding. Dissolution of relationships resulted from champions changing/leaving positions, engagement in transactional relationships, or limited mutual trust and respect. CONCLUSIONS: As universities and government agencies establish relationships and utilise opportunities to share ideas, envision change together, and leverage their collaborations to use evidence to inform decision-making, a new modus operandi becomes possible. Embracing the individual, institutional, networked and systems dynamics of relationships can lead to new practices, alternate approaches and transformative change. Government agencies, schools of public health and higher education institutions more broadly, should pay deliberate attention to identifying and managing the various drivers, enablers and disablers for relationship initiation and resilience in order to promote more evidence-informed decision-making.

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.

Health inequalities: a Research Positioning Exercise at the National Institute of Health, Italy.

BACKGROUND: The Italian National Institute of Health (Istituto Superiore di Sanità, ISS) considers health inequalities (HI) an important area of activity. As the scientific and technical body of the Ministry of Health and the National Health Service, ISS may play a key role to reduce HI. In order to enable ISS in addressing the new and crucial HI challenge, a Research Positioning Exercise was designed and implemented. METHODS: The Exercise included: (i) workshop to strengthen the institutional interest in the field of HI; (ii) review and analysis of ISS publications (years 2000-2017) to identify HI research topics; (iii) survey among ISS researchers regarding main research challenges to address HI in the coming years; and (iv) analysis of input on research challenges from HI international experts. RESULTS: The results of this Exercise suggest that the following points should be included in the future ISS agenda planning: (i) themes which ISS should continue working on (e.g. migrants/vulnerable groups); (ii) themes to be improved: (a) relationship between social determinants and mechanism of HI generation and (b) relationship between risk factors exposure and social determinants; and (iii) new themes to be addressed: (a) mechanisms underlying the resilience observed in Italy; (b) new socioeconomic indicators for HI monitoring; and (c) evidence-based policies aimed at reducing HI. CONCLUSION: Findings of this Exercise show that ISS researchers identified relevant areas, addressing inequalities in addressing the health. Because of ISS structural peculiarity that includes multidisciplinary expertise, the ISS could provide a significant contribution to HI research challenges and knowledge gaps.

The factors impeding health system reform in Iraqi Kurdistan region.

The relatively poor health outcomes in Iraq have been attributed to the inability to address the shortfalls in the public health model. Calls for health system reform in Iraqi Kurdistan Region started in 2004; however, few, if any, significant changes have been achieved since then. This research examines the factors impeding public health system reform in the Iraqi Kurdistan Region, as perceived by the health policy makers, through 11 in-depth, unstructured interviews. Participants attributed the delay in reform to 16 impeding factors that can be categorized into 5 major themes: historical, ethical, cultural, political and institutional. The intricate network of these inter-dependent factors provides a possible explanation for the failure or unsustainability of reform efforts. Reform initiatives might have a better chance of success if they take into consideration the well-established and unique background and social construct in Iraq, as well as the impact of decades of conflict and insecurity, both of which influence the individual and institutional reasoning and behaviour across the entire health system.

Determinants of organ donation registration.

Rates of organ donor registration range from 20% to 60% throughout the United States. The purpose of this study was to examine sociogeographic differences in organ donor registration rates throughout Missouri to identify varying patterns The organ donor registration rate from each Department of Motor Vehicle office in Missouri was extracted from the National Organ Registration database, office locations were geocoded, and census tract level sociodemographic characteristics were extracted. Spatial regression analyses were conducted to identify relationships between location of DMV offices and census tract-level concentrated disadvantage. Census tract-level concentrated disadvantage (education attainment, poverty, single-headed households) had a significant negative relationship with organ donor registration rates. Yet, census tract-level African American/Black resident concentration was not significantly related to organ donor registration rates. These findings suggest that race-based interventions to recruit organ donors may no longer be necessary. Yet, identifying how characteristics of concentrated disadvantage may be more influential in determining organ donor registration. Gaining a better understanding of how individual decisions are made is integral in the context of increased life expectancy in conjunction with the complex management of chronic conditions.

Building Synergy between Regulatory and HTA Agencies beyond Processes and Procedures-Can We Effectively Align the Evidentiary Requirements? A Survey of Stakeholder Perceptions.

OBJECTIVES: To evaluate the current practice of companies and agencies to assess the changes made in aligning regulatory and health technology assessment (HTA) stakeholders; to identify areas of commonality of evidentiary requirements that could occur; and to identify strategic issues and trends of regulatory and HTA synergy. METHODS: Two separate questionnaires were developed to assess stakeholders' perceptions on regulatory and HTA alignment, one for pharmaceutical companies and the other for regulatory and HTA agencies. The responses were analyzed using descriptive statistics. RESULTS: Seven regulatory and 8 HTA agencies from Australia, Canada, and Europe and 19 international companies developing innovative medicine responded to the survey. This study provided a snapshot of the current regulatory and HTA landscape. Changes made over the past 5 years were reflected in three main areas: there is an increasing interaction between regulatory and HTA agencies; current conditional regulatory approvals are not always linked with flexible HTA approaches; and companies are more supportive of joint scientific advice. Four types of evidentiary requirements were identified as building blocks for better alignment: acceptable primary end points, inclusion of an active comparator, use of patient-reported outcomes, and choice and use of surrogate end point. CONCLUSIONS: The study showed that the gap between regulatory and HTA requirements has narrowed over the past 5 years. All respondents supported synergy between regulatory and HTA stakeholders, and the study provided several recommendations on how to further improve evidentiary alignment including the provision of joint scientific advice, which was rated as a key strategy by both agencies and companies.

Evolution of a holistic systems approach to planning and managing road safety: the Victorian case study, 1970-2015.

BACKGROUND: The Victorian Safe System approach to road safety slowly evolved from a combination of the Swedish Vision Zero philosophy and the Sustainable Safety model developed by the Dutch. The Safe System approach reframes the way in which road safety is viewed and managed. METHODS: This paper presents a case study of the institutional change required to underpin the transformation to a holistic approach to planning and managing road safety in Victoria, Australia. RESULTS: The adoption and implementation of a Safe System approach require strong institutional leadership and close cooperation among all the key agencies involved, and Victoria was fortunate in that it had a long history of strong interagency mechanisms in place. However, the challenges in the implementation of the Safe System strategy in Victoria are generally neither technical nor scientific; they are predominantly social and political. While many governments purport to develop strategies based on Safe System thinking, on-the-ground action still very much depends on what politicians perceive to be publicly acceptable, and Victoria is no exception. CONCLUSIONS: This is a case study of the complexity of institutional change and is presented in the hope that the lessons may prove useful for others seeking to adopt more holistic planning and management of road safety. There is still much work to be done in Victoria, but the institutional cultural shift has taken root. Ongoing efforts must be continued to achieve alert and compliant road users; however, major underpinning benefits will be achieved through focusing on road network safety improvements (achieving forgiving infrastructure, such as wire rope barriers) in conjunction with reviews of posted speed limits (to be set in response to the level of protection offered by the road infrastructure) and by the progressive introduction into the fleet of modern vehicle safety features.

Obfuscating transparency?

Several recent and prominent articles in Science and Nature deliberately mischaracterized the nature of genuine scientific evidence. Those articles take issue with the United States Environmental Protection Agency's recent proposal to structure its policies and rules only from studies with transparently published raw data. The articles claim it is an effort to obfuscate with transparency, by eliminating a host of studies not offering raw data. A remarkable declaration by a Science editorial is that properly trained experts can verify the scientific evidence of studies without access to raw data, We assert the Agency's proposal must be sustained. Transparency in reporting is a fundamental ethical imperative of objective scientific research justifying massive official regulations and policies. Putative hazards bereft of independent scientific evidence will continue to stoke public anxieties, calling for precautionary regulations and policies. These should rely not on spurious science but on transparent tradeoffs between the smallest exposures compatible with utility and with social perceptions of affordable precaution.

Let the IRIS Bloom:Regrowing the integrated risk information system (IRIS) of the U.S. Environmental Protection Agency.

The Integrated Risk Information System (IRIS) of the U.S. Environmental Protection Agency (EPA) has an important role in protecting public health. Originally it provided a single database listing official risk values equally valid for all Agency offices, and was an important tool for risk assessment communication across EPA. Started in 1986, IRIS achieved full standing in 1990 when it listed 500 risk values, the effort of two senior EPA groups over 5 years of monthly face-to-face meetings, to assess combined risk data from multiple Agency offices. Those groups were disbanded in 1995, and the lack of continuing face-to-face meetings meant that IRIS became no longer EPA's comprehensive database of risk values or their latest evaluations. As a remedy, a work group of the Agency's senior scientists should be re-established to evaluate new risks and to update older ones. Risk values to be reviewed would come from the same EPA offices now developing such information on their own. Still, this senior group would have the final authority on posting a risk value in IRIS, independently of individual EPA offices. This approach could also lay the groundwork for an all-government IRIS database, especially needed as more government Agencies, industries and non-governmental organizations are addressing evolving risk characterizations.

Prevalence of adverse birth outcome and associated factors among women who delivered in Hawassa town governmental health institutions, south Ethiopia, in 2017.

BACKGROUND: Most pregnancies are unplanned in Ethiopia. This is due to ignorance of the types and efficacy of each method of contraception they are associated with vast and unpredictable complications. Most of the time, these complications result in adverse birth outcomes. Information about prevalence of adverse birth outcome and it's factors are relevant for designing, and initiating and intervening programs to decrease these undesirable out comes. OBJECTIVE: To assess prevalence of adverse birth outcome and associated factors among women who delivered in Hawassa town governmental health institutions, south Ethiopia, in 2017. METHOD: We conducted institutional based cross sectional study among 580 pregnant women from december1-30/2017, by multistage systematic random sampling method in governmental health institution in Hawassa town. Data were collected through structured pre-tested, close ended and interview administered questionnaire in their post-partum period. Collected data was entered in Epi-info version 7 and analyzed using SPSS. Odds ratio with 95% confidence interval on multivariable logistic regression was computed and P-value< 0.05 considered as significance. RESULT: From a total of 580 respondents 106(18.3%) respondent's had child related adverse birth outcome. Previous History of child related adverse pregnancy outcome 4.2 (95%,CI = 2.5-6.9), Attend at list one antenatal care visit 2.3 (95%CI = 1.1-4.3), Own cat in the house 2.2 (95%,CI = 1.3-3.7), Had any chronic disease/s 2.1(95%,CI = 1.1-4.8), Age of the mother (from 35 to 45 Years) 2.3(95%,CI = 1.1-4.8), Poor participants' Knowledge on preconception care 3 (95%CI = 1.4-1.6) were significant predictor of adverse birth outcome in this study . CONCLUSION AND RECOMMENDATION: Prevalence of adverse birth outcome was found to be significant in the current study. Presence of Previous History of adverse pregnancy outcome, on ante-natal attendance, presence of cat in the house, presence of chronic disease/s, younger mother and Poor Knowledge of preconception care were significant predictor of adverse pregnancy outcome. Therefore it is better to give more attention on expanding preconception and antenatal care. Creating awareness about family planning methods type and efficacy for women of reproductive health is mandatory. Services, increasing health education on personal hygiene vaccination of cats. Moreover, early detecting and treatment of chronic disease.

Shifting to Value-Based Principles in Sickness Insurance: Challenges in Changing Roles and Culture.

Purpose Management principles in insurance agencies influence how benefits are administered, and how return to work processes for clients are managed and supported. This study analyses a change in managerial principles within the Swedish Sickness Insurance Agency, and how this has influenced the role of insurance officials in relation to discretion and accountability, and their relationship to clients. Methods The study is based on a qualitative approach comprising 57 interviews with officials and managers in four insurance offices. Results The reforms have led to a change in how public and professional accountability is defined, where the focus is shifted from routines and performance measurements toward professional discretion and the quality of encounters. However, the results show how these changes are interpreted differently across different layers of the organization, where New Public Management principles prevail in how line managers give feedback on and reward the work of officials. Conclusions The study illustrates how the introduction of new principles to promote officials' discretion does not easily bypass longstanding management strategies, in this case managing accountability through top-down performance measures. The study points out the importance for public organizations to reconcile new organizational principles with the current organizational culture and how this is manifested through managerial styles, which may be resistant to change. Promoting client-oriented and value-driven approaches in client work hence needs to acknowledge the importance of organizational culture, and to secure that changes are reflected in organizational procedures and routines.

[Temporary approval for intranasal naloxone: Setting up in a French addiction center]. / Pratique de l'ATU de cohorte de la naloxone intranasale (Nalscue®) : mise en place dans un CSAPA parisien.

Intranasal naloxone aims at preventing opioid overdose related deaths in active drug users. In France, it has been available since July 2016 through a temporary approval which requires a hospital-based pharmacy and a nominative registration of each patient. We present the characteristics of the first patients who could receive this prescription in our hospital-based addiction center and how they used naloxone during follow-up. Results favor a larger dispensing of naloxone. Patients' as well as peers' and families' education is needed.