Factors influencing the effects of policies and interventions to promote the appropriate use of medicines in high-income countries: A rapid realist review.

BACKGROUND: The appropriate use of medicines has long been recognized as a fundamental component of medicine policies. We aimed to extract lessons from published research on how policy contexts and mechanisms can affect the outcomes of national- or health-system level interventions to promote appropriate medicine use (defined as an increase in underutilized medications or decrease in inappropriate medication use). METHODS: We conducted a rapid realist review of published evidence concerning system-level policies to promote the appropriate use of medicines in high-income countries with universal prescription drug coverage. We searched MEDLINE and Embase to identify relevant publications. We used a realist evaluation framework to identify contexts, mechanisms, and outcomes for each intervention and to hypothesize which policy contexts and mechanisms supported successful outcomes in terms of relative changes in the prevalence of use of the specific medication classes targeted. RESULTS: From 1,318 identified studies, 18 met our inclusion criteria. 13 distinct policies were identified. Three main policy-related factors underpinned successful interventions: involving providers and patients through program interventions; central coordination through national agencies dedicated to medicine policies; and the establishment of an explicit and integrated national medicine policy strategy. CONCLUSION: Policymakers can improve coordination of national pharmaceutical policies to reduce harms from inappropriate medicines use, thus improving health outcomes through cost-effective programs.

The Coloniality of drug prohibition.

There have been several recent commentaries which have highlighted the relevance of the postcolonial perspective to drug prohibition and called for the decolonisation of drug policy (Daniels et al., 2021; Hillier, Winkler & Lavallée, 2020; Lasco, 2022; Mills, 2019). While these are significant interventions in the field, sparse drugs scholarship has engaged more directly with well-developed literature and concepts from Critical Indigenous Studies (Moreton-Robinson, 2016) and Indigenous Standpoint Theory (Moreton-Robinson, 2013; Nakata, 2007) and reflected on its applicability to the drug and alcohol field. In contrast to the postcolonial perspective, which understands colonisation as a historical event with contemporary impacts, Indigenous scholarship conceptualises colonisation as an active and ongoing part of how the settler-state continues to impose itself. From this vantage point I explore coloniality as a system of power and reflect on the way prohibition acts as a key arm of the settler-colonial state. The paper explores the way concepts like vulnerability, marginality, overrepresentation, disproportionality and addiction involve colonial violence, knowledge practices and narratives which are central to the way coloniality is maintained and continues to assert itself in contemporary settler societies.

Buprenorphine dispensing before and after the April 2021 X-Waiver exemptions: An interrupted time series analysis.

BACKGROUND: Until the end of 2022, a special registration, known as the X-waiver, was required to prescribe buprenorphine in the US. Before its removal, US federal regulations trialed an X-waiver exemption, initiated on April 28, 2021, which permitted buprenorphine prescribing for up to 30 patients without additional training. We aimed to understand if these regulatory changes impacted buprenorphine dispensing. METHODS: We conducted an interrupted time series analysis to understand changes in buprenorphine dispensing during the 26 weeks after the X-waiver exemption compared to the expected baseline trend established in the 26 weeks before using the IQVIA Longitudinal Prescription claims database. The primary outcome was number of new buprenorphine prescribers nationwide (defined as no prior buprenorphine prescription dispensed in the last 26 weeks). Segmented regression estimated relative changes in buprenorphine dispensing at 1, 13, and 26 weeks post-X-waiver change. RESULTS: A total of 15,517,525 prescriptions filled for 1,328,172 patients (43.4 % female) ordered by 62,312 providers were included for analysis. At 26 weeks post-X-waiver change, there was no change in the number of new prescribers compared to the expected baseline trend (-2.7 % [95 % CI:-8.3,2.9]). The number of new (15.2 % [4.6,25.8]) and existing (1.7 % [0.9,2.4]) patients and patients per prescriber (4.3 % [3,5.6]) increased. Buprenorphine prescriptions reimbursed by Medicaid increased (7.5 % [6.6,8.4]) while commercial fills decreased (-3.4 % [-5.3,-1.5]). CONCLUSIONS: The number of new prescribers did not increase six months post-X-waiver exemption while new patients continued to enter treatment at higher-than-expected rates. These findings suggest that additional interventions beyond the recent X-waiver removal may be needed to increase access to buprenorphine.

A Future European Scientific Dialogue Regulatory Framework: Connecting the Dots.

The regulatory framework of the European Union (EU) offers multiple and valuable options for Scientific Advice (SA). However, at a time of increasing scientific complexity and global competition, navigating the SA landscape may be challenging. Such challenges are related to the technicalities of the framework itself, as well as to fundamental changes in the development of promising therapeutics. This article provides an overview of these challenges and reflects on the ways in which the already available SA options could be consolidated and optimized for building an integrated, easy-to-navigate process. The key elements of the proposal are improved orientation and navigation support, a simplified process of managing parallel interactions with multiple bodies, competitive SA timelines, consistency and harmonization across stakeholders, a strengthened horizon scanning to increase network preparedness, and a mechanism for building an institutional memory. The article builds on ongoing dialogues driven by the European Medicines Agency and the European Medicines Regulatory Network, and contributes the viewpoint of the European Federation of Pharmaceutical Industries on the ways in which the EU SA framework needs to evolve to provide effective Scientific Dialogue throughout the medicine lifecycle. The article is timely because of the current discussion on the future Scientific Dialogue framework and may inform forthcoming legislative changes in the draft General Pharma Legislation revision and how they are practically implemented.

Improving Drug Supply Chain Security.

This Viewpoint discusses the importance of the Drug Supply Chain Security Act and the need for pharmaceutical supply chain safeguards.

Outer packaging labelling of medicines in Southern African Development Community (SADC) countries: comparative analysis of requirements and transition terms for harmonisation.

INTRODUCTION: The COVID-19 pandemic highlighted an urgent need for harmonised requirements for the regulation of medicines. To fully implement harmonised medicines regulations across Africa, common technical standards of medicine regulations are needed. One such technical standard is the labelling of medicines on outer packaging. In this study, we compared outer packaging labelling requirements and transition terms for harmonization for countries in the Southern African Development Community (SADC) region. METHODS: Data on legislation and/or regulatory guidelines for medicine outer packaging labelling from National Medicines Regulatory Authorities (NMRAs) were obtained for countries in the SADC region (n = 16) by February 2023. A detailed comparative content analysis was conducted to determine alignment with the requirements of the Southern African Development Community (SADC) harmonised labelling guidelines to assess readiness levels of each country to transition to the SADC harmonised labelling guideline for outer packaging of medicines. RESULTS: Content analysis showed at least 11 out of 16 countries require national legal reform to transition to the SADC harmonised labelling guideline. In all cases where countries specified labelling requirements for outer packaging of medicines, these were stipulated in national medicines legislation. CONCLUSION: Even though there is a high level of alignment across the countries in terms of national labelling requirements, most countries in the SADC region would still require national legislative reform to transition to regional harmonised labelling requirements and then ultimately to continental requirements of the African Medicines Agency (AMA).

[The application of real-world evidence in drug regulatory decision-making]. / Die Anwendung von Real-world-Evidenz in Entscheidungsprozessen der Arzneimittelregulation.

Drug regulation is a system to support and protect public health. Drugs with market access must be effective, safe and of high quality. Therefore, drug regulatory decision-making by the competent authorities is made on a scientific basis. Real-world evidence (RWE) from real-world data (RWD) has so far predominantly been taken into account in a supportive manner in drug regulatory decision-making with regard to drug safety after marketing authorisation. The extensive potential of RWE for regulatory decision-making processes along the entire product life cycle has been increasingly used and further examined in recent years.This article provides an overview of current applications of RWE in drug regulatory decision-making processes. The potentials of RWE along with the hurdles to be addressed are described and examples of current projects on RWE research for drug regulation are given. The work is based on current international literature as well as examples from international and European initiatives and regulatory practice, which aim to support an increased use of RWD/RWE in regulatory decision-making processes. In order to be able to utilise the potential of RWE even more in the future, it is important to make relevant RWD sources more readily available through research projects and initiatives, to further develop evaluative methods and to establish the significance of RWE.

Implied Claims in Drug Advertising: A Review of Recent Literature and Regulatory Actions.

Federal agencies and self-regulatory bodies help to ensure prescription and nonprescription drug promotion contains accurate information; however, false or misleading claims may cause people to have inaccurate perceptions of a drug and inhibit their ability to make informed decisions. We conducted a systematic review assessing evidence from 2012-2021 on how consumers and healthcare providers (HCPs) interpret claims made indirectly or through inference (implied or implicit claims) as well as synthesizing prescription and nonprescription drug advertising claims that have been the subject of regulatory actions from 2017-2021. Our search identified 16 studies from the peer-reviewed literature and 26 letters or case reports issued by the Food and Drug Administration (FDA) or National Advertising Division (NAD). Results from peer-reviewed studies suggest that implied claims can result in inferences that may not be warranted by the material facts about the drug. Perceptions of a drug's efficacy and, to a lesser extent, risk, are influenced by implied and explicitly false claims in prescription drug promotion. Claims related to implied superiority and overstatement of efficacy were the most prevalent claims flagged for review and examined in the literature. These types of claims were also the subject of many of the compliance actions by the FDA and case reports from the NAD. More research is needed to understand how people interpret varying types of implied claims and the impact of such claims on key outcomes. From a policy standpoint, understanding how people interpret implied claims can inform how the FDA approaches these claims in the marketplace.

Expanding regulatory science: Regulatory complementarity and reliance.

Drug regulatory institutions, infrastructures, and systems are becoming increasingly interconnected across national boundaries and increasingly global in outlook. This process is reflected in the broadening and deepening application of the principles and practice of Regulatory Reliance, and parallel initiatives to strengthen the capacities of regulatory institutions in low- and middle-income countries (LMICs). Although these developments are important and constructive, they have tended to be framed in terms of the transfer of systems, knowledge, and skills from relatively "mature" regulatory agencies in high-income countries (HICs) to less-well-resourced regulatory agencies in LMICs. This framing recognizes and foregrounds the considerable practical challenges that many LMIC regulatory agencies face, but in doing so, also backgrounds and underestimates the significance of the different contextual insights that LMIC health researchers and regulators can bring to the regulatory deliberations of their HIC counterparts. This position paper argues that the systematic pursuit, identification, and sharing of these different contextual insights-a dimension of regulatory science that we term "Regulatory Complementarity"-can augment the current practice and goals of Regulatory Reliance, and further invigorate the emerging global regulatory ecosystem.

Clinical research and drug regulation in the challenging times of individualized therapies: A pivotal role of clinical pharmacology.

Since the 1980s, medical specialists in Clinical Pharmacology have been playing a crucial role in the development of drug regulation in Spain. In this article we report on the activities carried out and the prospects for development in three very relevant areas from the regulatory perspective: 1) the development of stable public infrastructures to facilitate non-commercial clinical research with medicines, 2) the regulatory aspects of individual access to medicines in special situations, beyond their regular access after marketing approval and funding by the National Health System, and 3) the challenges of development and access to advanced therapies, with special reference to the figure of the hospital exemption.

Methodological guidelines and publications of benefit-risk assessment for health technology assessment: a scoping review protocol.

BACKGROUND: Benefit-risk assessment (BRA) is used in multiple phases along the health technology's life-cycle to evaluate the balance between the benefits and risks, as it is fundamental to all stakeholders. BRA and its methodological approaches have been applied primarily in the context of regulatory agencies. However, BRA's application and extent in the context of health technology assessment (HTA) bodies remain less clear. Our goal is to perform a scoping review to identify and map methodological guidelines and publications on methods of BRA. This will be done considering the different phases of the life-cycle of health technologies to underline both the depth and extent of research concerning BRA, especially in the context of HTA. METHODS AND ANALYSIS: This scoping review protocol was developed following the framework proposed by Arksey and O'Malley, and the updated guidelines by the Joanna Briggs Institute. We will include methodological publications that provide recommendations or guidelines on methods for BRA. We will conduct electronic searches on Medline (PubMed) and EMBASE (Ovid) databases; manual searches on the main websites of HTA bodies and drug regulatory organisations; and contact experts in the field. Systematic extraction forms will be used to screen and assess the identified publications by independent assessors. We will provide a qualitative synthesis using descriptive statistics and visual tools. Results will be summarised in systematic evidence tables and comparative evidence scoping charts. ETHICS AND DISSEMINATION: This review will use data publicly available and does not require ethics approval. The results of this scoping review will contribute to scientific knowledge and act as a basis for methodologists, guideline developers and researchers for the development of BRA to inform regulatory decisions, reimbursement and coverage decision making. The results will be disseminated through peer-reviewed articles, conferences, policy briefs and workshops. TRIAL REGISTRATION NUMBER: Open Science Framework (https://doi.org/10.17605/OSF.IO/69T3V).

INTRODUCTION: Rethinking Pharmaceutical Policies in Latin America and the Caribbean: An Overview.

The demographic and epidemiological transitions are driving pharmaceutical expenditures up in Latin American and the Caribbean, with much of the cost falling on households. The domestic development and manufacturing of bio-similars could make medicines more affordable.

Regional regulatory harmonisation initiatives: Their potential contribution to the newly established African Medicines Agency.

BACKGROUND: Key regulatory entities can serve as building blocks for the African Medicines Agency (AMA). The aim of this study is to demonstrate how the regional medicines regulatory harmonisation programmes could contribute to AMA's effectiveness and efficiency. METHODS: A literature search was conducted using key words to identify publications about the AMA, African Medicines Regulatory Harmonisation (AMRH) and East African Community Medicines Regulatory Harmonisation programmes (EAC-MRH) from 2009 to 2023. The EAC-MRH programme experience was used to highlight the benefits and challenges of African regulatory harmonisation. RESULTS: As the foundation for the AMA, the AMRH has established structures and workstreams to support its operationalisation, including 10 Technical Committees (TCs) and 5 Regional Economic Committees (RECs). Lessons learned from the EAC-MRH 10-year experience are being used to scale up regulatory harmonisation and could be of value to AMA harmonisation experience. CONCLUSIONS: As of June 2023, 35 of 55 countries have either signed and/or ratified the AMA Treaty, whilst 20 have neither signed nor ratified it. An effective AMA will need strong National Medicines Regulatory Authorities as well as Regional programmes and it is imperative for more well-resourced countries to ratify the treaty to ensure access to essential medical products and technologies for the African people.

Emerging trends: the involvement of community pharmacists in the planning and execution of pharmaceutical policies and economics.

INTRODUCTION: The aim of this study was to analyze existing research on the involvement of community pharmacists in the planning and execution of pharmaceutical policies and economic strategies. METHODS: The researcher searched five scholarly databases: Medline, BioMed Central (BMC), Excerpta Medica Database (EMBASE), ProQuest, and PubMed for the reviewed articles. The search and selection of the articles involved searching each of the databases using specific keywords and a combination of them to form phrases and the Boolean search string. The researcher adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in developing this study. RESULTS: From the original search, a total of 537 articles emerged from which 17 articles remained upon screening. Findings show that the community pharmacy role has expanded over the past years to enable pharmacists serve diverse roles, but there is a high lack of involvement of these stakeholders in the planning and execution of policies. The pharmaceutical and health-care sectors operate in a way that does not recognize nor engage community pharmacists sufficiently in the policy planning and execution. CONCLUSIONS: Relevant stakeholders need to create an enabling and supportive environment for utilizing the abilities, knowledge, and skills of community pharmacists in policy planning and execution.

Reforming Paediatric Drug Regulations in Canada: A Clinical and an Access Imperative.

Children deserve the same high standards for drug safety, efficacy and access as adults. Unfortunately, Canada lags behind leading international regulators in implementing reforms to ensure access to paediatric medications. Paediatric regulations, also known as paediatric rules in the US, include a mandate to submit paediatric data in all new drug applications when paediatric use can be anticipated. Absent paediatric regulations, many medications with paediatric-specific indications in other countries remain "off-label" for Canadian children. In addition to concerns related to off-label drug safety, the absence of paediatric indications prohibits appropriate paediatric-specific health technology assessments and limits the evidence-based listing of paediatric medications on public and private formularies.

Dynamic Regulatory Assessment: Unpacking the Process Reveals Readiness to Pilot for Europe-An EFPIA View.

The medicines regulatory network of the European Economic Area comprises 30 countries, their National Competent Authorities (NCA), and the European Medicines Agency (EMA). The NCAs and EMA are involved at different stages of the medicine life cycle; not all are engaged in a particular medicine's development discussions. As a result, knowledge management (ie, acquisition and transfer between medicine developer and the NCAs) is fragmented and inefficient. Dynamic regulatory assessment (DRA), a regulatory science concept developed by the European Federation of Pharmaceutical Industries and Associations (EFPIA), could drive increased connectedness supporting more continuous knowledge building. DRA works via iterative release and assessment of discrete data packets (DDPs) at mutually agreed milestones during development, culminating in more efficient development and faster authorization. This commentary seeks to build on an earlier article by unpacking the DRA concept, with a particular focus on DDPs. Its aim is to show how DDPs can support efficient and predictable release of data to encourage development and assessment of promising medicines, and it makes the case for piloting the DRA concept with European regulators now.