Mistakes were not make…
Timeframe 2011–2020 ✅
Decade of Vaccines Collaboration
GVAP was the product of the DoV Collaboration, an unprecedented effort that brought together development, health and immunization experts and stakeholders. The leadership of the Bill & Melinda Gates Foundation, GAVI Alliance, UNICEF, United States National Institute of Allergies and Infectious Diseases and WHO, along with all partners – governments and elected officials, health professionals, academia, manufacturers, global agencies, development partners, civil society, media and the private sector – are committed to achieving the ambitious goals of the GVAP. Many more are expected to add their support in the future as the plan is translated and implemented at the country and regional levels.
The Global Vaccine Action Plan (GVAP)—endorsed by the 194 Member States of the World Health Assembly in May 2012—is a roadmap to prevent millions of deaths by 2020 through more equitable access to vaccines for people in all communities. The GVAP aims to strengthen routine immunization, introduce new and improved vaccines, and advance research and development for the next generation of vaccines and technologies.
Why is the link from the official WHO website not available? https://www.who.int/publications-detail-redirect/global-vaccine-action-plan-2011-2020
Background information
Decade of Vaccines Collaboration
The DoV Collaboration brought together diverse stakeholders to develop the GVAP to stimulate the discovery, development and delivery of lifesaving vaccines. The plan builds on the success of current work to transform the way vaccines move from formulation, to factory, to families.
Decade of Vaccines commitment to Every Woman Every Child
Plan or Coincidence?
This is all criminal by design!
Integrate society in science and innovation issues, policies and activities in order to integrate citizens‘ interests and values and to increase the quality, relevance, social acceptability and sustainability of research and innovation outcomes in various fields of activity from social innovation to areas such as biotechnology and nanotechnology
https://ec.europa.eu/programmes/horizon2020/en/h2020-sections-projects
Expert group on the economic and societal impact of research and innovation (ESIR)
What the ESIR expert group does, membership details, terms of reference and contact details
Safety Guidelines
ICH has produced a comprehensive set of safety Guidelines to uncover potential risks like carcinogenicity, genotoxicity and reprotoxicity. A recent breakthrough has been a non-clinical testing strategy for assessing the QT interval prolongation liability: the single most important cause of drug withdrawals in recent years.
INTERNATIONAL COUNCIL FOR HARMONISATION OF TECHNICAL REQUIREMENTS FOR PHARMACEUTICALS FOR HUMAN USE – ICH HARMONISED GUIDELINE
NONCLINICAL BIODISTRIBUTION CONSIDERATIONS FOR GENE THERAPY PRODUCTS
Concept Paper
S12: Nonclinical Biodistribution Considerations for Gene Therapy Products
Dated 18 November 2019
Endorsed by the Management Committee on 18 November 2019
https://database.ich.org/sites/default/files/S12_FinalConceptPaper_2019_1118.pdf
Final Business Plan
S12: Nonclinical Biodistribution Considerations for Gene Therapy Products Dated 18 November 2019
Presentation
Endorsed by the Management Committee on 18 November 2019
https://database.ich.org/sites/default/files/ICH_Step_4_Presentation_ICH%20S12_2023_0306_0.
ICH HARMONISED GUIDELINE
NONCLINICAL BIODISTRIBUTION CONSIDERATIONS FOR GENE THERAPY PRODUCTS
Final version Adopted on 14 March 2023
EC, Europe – Implemented; Date: 30 September 2023; Reference: EMA/CHMP/ICH/318372/2021
https://database.ich.org/sites/default/files/ICH_S12_Step4_Guideline_2023_0314_WithCorrection_0.pdf
ICH S12 Nonclinical Biodistribution Considerations for Gene Therapy Products
Step 4 document – to be implemented 6 March 2023
Project on a Framework for Rating Evidence in Public Health (PRECEPT)
Robert Koch Institute (RKI), Berlin, Germany
Project coordinator: Dr. Thomas Harder
Project partners
Members/institutions of the Operational Group:
- Robert Koch Institute (RKI), Berlin, Germany
Members/institutions of the Technical Advisory Group:
- Department of Technology and Social Change, Linköping University, Sweden
- Department of Clinical Epidemiology & Biostatistics, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada
- German Cochrane Centre, Freiburg, Germany
- Glasgow Caledonian University, Glasgow, United Kingdom
- Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE)
- Developing and Evaluating Communication Strategies to Support Informed Decisions and Practice Based on Evidence (DECIDE)
- Institute for Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University Munich, Germany
- National Institute for Health and Clinical Excellence (NICE), United Kingdom
- Norwegian Institute of Public Health, Oslo, Norway
- Scottish Intercollegiate Guidelines Network (SIGN), United Kingdom
Funding
European Centre for Disease Prevention and Control (ECDC).
Background
The Project on a Framework for Rating Evidence in Public Health (PRECEPT) has been established to develop a methodology for evaluating and grading evidence in the field of infectious disease epidemiology, prevention and control to be applied in the European region. The project – under the lead of the Robert Koch Institute – is carried out by a multidisciplinary team involving experts with well-documented experience in the fields of infectious disease epidemiology and prevention, evidence-based public health (EBPH), systematic reviews and meta-analyses as well as development of evidence appraisal and grading systems. Members of the project team are engaged in a variety of international institutions, organizations, and working groups in the Public Health area, thereby providing profound expert knowledge in the field of EBPH methodology, methods development, and application of evidence appraisal instruments.
Public health recommendations in the area of infectious disease epidemiology, prevention, and control should draw on reliable research to inform decisions. In the field of clinical medicine, particularly regarding treatment options, guidance is developed using the approach of Evidence-based Medicine (EBM). In recent years, debates have centered on the applicability of the clinical EBM model to the field of public health and infectious disease prevention and control. Though EBM started out as an attempt to track the best available external evidence to address healthcare questions, this framework has resulted in evidence-appraisal practices that assume a hierarchy of study designs, with randomized controlled trials being ranked high, whereas observational studies a priori are considered to provide lower quality of evidence. In the field of Evidence-based Public Health, however, often more complex interventions or evidence exclusively derived from non-interventional studies have to be assessed. In particular, in infectious disease epidemiology potentially relevant information often comes from studies which differ considerably in their design from RCTs, such as case series, incidence studies, surveillance data and outbreak reports. For a number of such study designs no established criteria exist for rating of study quality, causing difficulties in grading evidence based on these study types. Given this background, there is a need for a comprehensive framework for rating evidence in the field of infectious disease epidemiology, prevention and control that can assist European public health institutions in developing recommendations.
PRECEPT I
(August 2012 – July 2014)
Aim of PRECEPT I was to develop and pilot a systematic, transparent and comprehensive evidence assessment framework for rating the evidence and strength of recommendations in the area of public health based on published literature and the expertise of a multidisciplinary team in close collaboration with the ECDC. The developed framework will focus on topics and questions that are relevant for guidance development and decision-making in the area of infectious diseases prevention and control, and will not be limited to topics and questions related to interventions.
Results: During the first project phase, the project team conducted a systematic review of quality appraisal tools, provided an overview on previous applications of the GRADE methodology in the field of infectious disease prevention and control and organized an international expert meeting to discuss a draft framework that was developed by the project team (for details see Publications). According to the results of the peer review process which included the expert meeting and further rounds of consultations, a final version of the framework was developed and submitted to ECDC in March 2014.
PRECEPT II
(November 2014 – June 2018)
The second project phase builds upon this first version of the framework. Aim of PRECEPT II is to further elaborate the framework for rating the evidence and strength of recommendations in the area of Public Health / infectious diseases prevention and control developed by PRECEPT, in close collaboration with ECDC, and using the expertise of the multidisciplinary team. Furthermore, aim of the project is to suggest a methodology to translate evidence into recommendations, and to develop a user-friendly handbook and learning materials for future users of the framework.
Results: After a process of further refinements, the PRECEPT framework has been accepted for publication (forthcoming soon in Publications). In its current version, the framework is intended to rate scientific evidence related to four major domains of studies: burden of disease, risk factors for disease, diagnostics and intervention. The framework is grouped into four steps, starting from a complex public health question and ending with an evidence statement for each relevant domain. In step 1, approaches are described for identification of relevant questions. In step 2, methodological guidance is provided for the conduct of systematic reviews for these questions. For appraisal of methodological quality of identified studies, 15 different quality appraisal tools are proposed and an algorithm is given to match a given study design with an appropriate tool. In step 3, a standardized evidence grading scheme using the GRADE methodology is provided to rate the certainty of a body of evidence. The findings are documented in evidence profiles and summary of finding tables. The final step (step 4) consists of the preparation of a narrative evidence summary.
Currently, a user-friendly handbook for the framework is being developed.
Further resources
- PRECEPT Framework (PDF, 406 KB, File does not meet accessibility standards.)
- Framework Appendix A (PDF, 138 KB, File does not meet accessibility standards.)
- Framework Appendix B (PDF, 76 KB, File does not meet accessibility standards.)
- Framework Appendix C (PDF, 5 MB, File does not meet accessibility standards.)
- Framework Appendix D (PDF, 42 KB, File does not meet accessibility standards.)
- Literature review of previous GRADE applications (14.1.2014) (PDF, 158 KB, File does not meet accessibility standards.)
Date: 29.09.2017
FULL FACT SHEET FOR HEALTHCARE PROVIDERS
1 EMERGENCY USE AUTHORIZATION
The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the emergency use of Moderna COVID-19 Vaccine (2023-2024 Formula) for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 6 months through 11 years of age.
Justification for Emergency Use of Vaccines During the COVID-19 Pandemic
There is currently an outbreak of COVID-19 caused by SARS-CoV-2. The Secretary of the
Department of Health and Human Services (HHS) has:
• Determined that there is a public health emergency, or a significant potential for a public health emergency related to COVID-19.1
• Declared that circumstances exist justifying the authorization of emergency use of drugs and biological products during the COVID-19 pandemic.2
An EUA is an FDA authorization for the emergency use of an unapproved product or unapproved use of an approved product (i.e., drug, biological product, or device) in the United States under certain circumstances including, but not limited to, when the Secretary of HHS declares that the use of EUA authority is justified, based on a determination that there is a public health emergency, or a significant potential for a public health emergency, that affects or has a significant potential to affect, national security or the health and security of United States citizens living abroad, and that involves biological agent(s) or a disease or condition that may be attributable to such agent(s). Criteria for issuing an EUA include:
• The biological agent(s) can cause a serious or life-threatening disease or condition;
• Based on the totality of the available scientific evidence (including data from adequate
and well-controlled clinical trials, if available), it is reasonable to believe that:
⁃ 1 See U.S. Department of Health and Human Services, Determination of a Public Health Emergency and Declaration that Circumstances Exist Justifying Authorizations Pursuant to Section 564(b) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3. February 4, 2020; https://www.federalregister.gov/documents/2020/02/07/2020-02496/determination-of-public-health-emergency.
⁃ See also U.S. Department of Health and Human Services, Amended Determination of a Public Health Emergency or Significant Potential for a Public Health Emergency Pursuant to Section 564(b) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b). March 15, 2023 (“Amended Determination”); https://www.federalregister.gov/documents/2023/03/20/2023-05609/covid-19-emergency-use-authorization-declaration.
⁃ 2 See U.S. Department of Health and Human Services, Declaration that Circumstances Exist Justifying Authorizations Pursuant to Section 564(b) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3, 85 FR 18250 (April 1, 2020); https://www.federalregister.gov/documents/2020/04/01/2020-06905/emergency-use-authorization-declaration. See also Amended Determination (“The declarations issued pursuant to section 564(b)(1) of the FD&C Act that circumstances exist justifying the authorization of emergency use of certain in vitro diagnostics, personal respiratory protective devices, other medical devices and drugs and biological products, as set forth in those declarations, and that are based on the February 4, 2020 determination, remain in effect until those declarations are terminated in accordance with section 564 of the FD&C Act.”).
o The product may be effective in diagnosing, treating, or preventing the serious or life-threatening disease or condition;
o The known and potential benefits of the product – when used to diagnose, prevent, or treat such disease or condition – outweigh the known and potential risks of the product, taking into consideration the material threat posed by the biological agent(s); and
• There is no adequate, approved, and available alternative to the product for diagnosing, preventing, or treating the serious or life-threatening disease or condition.
Information Regarding Available Alternative Vaccines for the Prevention of COVID-19
PFIZER AND BIONTECH CHOOSE LEAD MRNA VACCINE CANDIDATE AGAINST COVID-19 AND COMMENCE PIVOTAL PHASE 2/3 GLOBAL STUDY https://web.archive.org/web/20210301235909/https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-choose-lead-mrna-vaccine-candidate-0
Evaluation of an outreach programme for patients with COVID-19 in an integrated healthcare delivery system: a retrospective cohort study https://pubmed.ncbi.nlm.nih.gov/38191255/
Randomized Controlled Trials Versus Real World Evidence: Neither Magic Nor Myth
Compared with drugs from the blockbuster era, recently authorized drugs and those expected in the future present a heterogenous mix of chemicals, biologicals, and cell and gene therapies, a sizable fraction being for rare diseases, and even individualized treatments or individualized combinations. The shift in the nature of products entails secular trends for the definitions of “drugs” and “target population” and for clinical use and evidence generation. We discuss that the lessons learned from evidence generation for 20th century medicines may have limited relevance for 21st century medicines. We explain why the future is not about randomized controlled trials (RCTs) vs. real-world evidence (RWE) but RCTs and RWE—not just for the assessment of safety but also of effectiveness. Finally, we highlight that, in the era of precision medicine, we may not be able to reliably describe some small treatment effects—either by way of RCTs or RWE.
THE CHANGING NATURE OF DRUGS
The great majority of drugs authorized during the “statin era” before the turn of the 21st century were chemicals (with very few biologicals), aiming for “blockbuster status.”2 By contrast, recently authorized drugs present a heterogenous mix of product types: of the 73 products containing a new active substance centrally authorized in the European Union between January 1, 2018, and December 31, 2019, 39 were chemicals, 29 were biologicals, and 5 were Advanced Therapies Medicinal Products (ATMPs; comprising cell, gene, and tissue engineered therapies). Twenty of 73 were designated orphan medicinal products, meaning that the prevalence of the target condition is < 5 of 10.000 in the European Union. An additional 8 were authorized for rare conditions but did not receive orphan status for a range of legal or regulatory reasons; hence, the total number of products for rare diseases is 28, that is close to 40% of all products containing a new active substance (for a complete list of products and characteristics, please see Table S1).
Based on the European Medicines Agency (EMA)’s in-house horizon scanning activities and predictions by other organisations,3 we are confident that the trend toward complex biologicals, ATMPs, and drugs for orphan diseases will accelerate over the coming decade. It has been estimated that by 2025, 10–20 cell and gene therapy products will be approved each year.4
The shift in the nature of products is relevant because it entails other secular trends for evidence generation. Most older drugs belonged to classes of compounds that are pharmacologically similar and intended for large groups of eligible patients; examples include statins, angiotensin receptor blockers, or proton pump inhibitors. With these compounds, the pharmacologic target of drug action and the drug-target interactions are essentially the same across most or all patients. Observed differences in clinical effect size across patient subpopulations can usually be explained by differences in down-stream pathologies or other between-patient differences external to the drug-target interaction per se. For example, the pharmacological drug targets for statins are the same across a number of subpopulations that can be defined by extra-pharmacological patient characteristics, such as primary prevention (a lower risk group) or secondary prevention (higher risk) groups. Consequently, it has been claimed that “valid estimates of the absolute benefits and harms of a treatment can be obtained by applying reliable randomized evidence for its separate proportional effects on each outcome of interest to the absolute incidence of these outcomes in observational studies conducted within a particular population.”1Where this assumption holds, results from RCTs may indeed be reasonably extrapolated across subpopulations (e.g., from higher risk to intermediate or even lower risk groups).5, 6
Circulating Biomarkers for Monitoring Chemotherapy-Induced Cardiotoxicity in Children – PubMed
Biomedicines. 2018 Mar; 6(1): 12. Published online 2018 Jan 29. doi: 10.3390/biomedicines6010012
PMCID: PMC5874669PMID: 29382133
Early and Late Onset Side Effects of Photodynamic Therapy
https://www.sciencedirect.com/science/article/pii/S2666555720300605
In light of the above and progress in scientific understanding of COVID-19, WHO, in collaboration with its COVAX partners and with key regional and national stakeholders, is updating both its initial goals for 2021 and the WHO Global COVID-19 Vaccination Strategy, looking at a 2021-2022 timeframe. The work intends to i) inform the decisions countries, policy makers and investors are making about their vaccination goals and targets for 2022 and beyond and ii) promote an equitable approach to COVID-19 vaccination globally, including through risk mitigation strategies.
The Global COVID-19 Vaccination Strategy July 2021 Update is being submitted to the WHO Strategic Advisory Group of Experts on Immunization (SAGE) for review, input and consideration for critical appraisal when it meets on 29 June 2021. Additional analysis will be conducted, and new evidence collected on an ongoing basis so that the strategy is periodically updated as warranted by the evidence, including individual country aspirations.
The WHO Global COVID-19 Vaccination Strategy proposes a Conceptual Goal Framework, identifying possible socio-economic and health goals countries can pursue with vaccination efforts, along a continuum. The framework is not meant to be exhaustive nor to endorse any specific combination of goals and vaccination targets, but rather lay out all the possible options for individual countries and the international community as a whole. The framework is intended to help countries make more explicit the rationale for their vaccination targets. In contrast to setting coverage targets as goal in themselves, the framework emphasizes the importance of defining explicit health and socio-economic goals and working towards equitable outcomes for all, both within and amongst countries.
The combinations of different socio-economic and health goals in the Goal Framework result in four qualitative levels of vaccination coverage that countries can pursue. The Framework encourages the use of the WHO Prioritization Roadmap to guide choice of target of populations at each level of ambition, while proposing a simplifying age descending order and age cut-offs for analytical purposes. For each of the goals and related vaccination coverage, the Global COVID-19 Vaccination Strategy document runs scenarios analysis on health impact, resource requirements and resource availability for vaccination levels. The analysis also identifies countries’ vaccination ambitions relative to the goal framework.
The Strategy documents that many countries are setting ambitious and diverse vaccination targets
driven by technical, political and economic considerations. Countries are racing upwards toward ambitious 50-70% coverage: for countries with much younger demographic distribution, mostly lower income settings, such targets imply vaccination of children and relatively important financial and system investments. The analysis of health impact shows that prioritizing vaccination of the oldest adults will achieve the greatest mortality and hospitalization reductions. While increasing the vaccination target to younger ages increases the overall number of events averted, it does so with differential efficiency across outcome measures: vaccinating those <30 years old is an efficient strategy mainly towards the goal of reducing viral transmission. This is where uncertainty begins: there are questions around ability of vaccines to reduce transmission, the need to do so relative to the unclear threat posed by Variants of Concern, the potential benefits of natural immunity, the full clinical impact of disease and infection, and gaps in evidence on the safety and performance of vaccines in children, among others.
While the biggest incremental benefit of moving to younger age strata is in lower income settings due to demographics, transmission patterns and constraints with the health system, trade-offs between ever increasing COVID-19 vaccination ambition and other health priorities is more evident. The risk is clear of impacting sustainability of immunization outcomes across many other disease of considerable burden. The risk is also clear in terms of foregone opportunities for expanding other immunization services.
These trade-offs need to be carefully weighed against the risks of lower and/or slower vaccination roll out in lower income settings in a fast-moving interconnected world. With cases on the rise, many settings could not only find themselves hit by high health costs, but also constrained by public health and social measures limiting consumption and socio-economic activity. In addition, economic losses due to reduced international trade and capital flows could be suffered. A choice, or lack of choice, to implement a limited vaccination target by low income settings will also have impact in higher income settings: both the International Chamber of Commerce and International Monetary Fund have clearly highlighted the role of an interconnected global value chain on economic gain or loss across all countries, with highest return on public investment in modern history of equitable global vaccination.
In addition to trade off-considerations, system and financial constraints can affect achievement of more ambitious country goals in LICs and LMICs, and potential booster requirements put into question sustainability of results. A ‘ramp up’ phase of vaccine implementation would require much higher throughput capabilities and this could be challenging in many settings. While financial resources would be difficult to mobilize, these are certainly not constrained: official development assistance, multilateral development loans, increased tax revenues from vaccination, are all available sources; many of these have already been committed. Nevertheless, systems, from health care workforce to cold chain to data and technologies may pose clear limits in constrained settings. To ensure all countries have similar opportunities, we need important external support for lower income settings, including technical and human resources. In addition, all countries, both lower and higher income, are likely to face challenges linked to potential need to adapt products as well as vaccine acceptance. In a last phase of the pandemic fight, tailoring efforts to reach the hard to reach will be essential.
On the vaccine supply side, this work shows a key opportunity for adequate global supply, but this will require very clear market signaling to supplier as well as collaborative behavior. We need anticipation of excess vaccine supplies, particularly in the coming months, and redistribution of surplus doses from higher to lower income settings as soon as possible, while urgently evaluate dose optimization strategies; supporting free cross-border flows of raw materials and finished vaccines; and, very importantly, early securing of manufacturing capacity scale up and diversification of vaccine productions providing increased access for developing countries, including through greater transparency.
This work highlights the following important considerations towards building consensus for an updated Global COVID-19 Vaccination Strategy:
- The path to full global recovery advances through several goals in a step wise approach from reducing highest risk of mortality and protecting health systems limiting most sever public health and social measures needed for crisis response to mitigating future health risks for full global recovery. The very first step in this chain represents an ‘unfinished agenda’ towards vaccination of the most vulnerable populations for which substantial investment is well under way. The second steps expands to larger share of adult population and is likely required to resume economic activity: this step is being actively pursued by many countries with important sunk investments; the analysis shows that with active market management and external technical and financial support, it could be at reach. The evidence that underpins the rationale for further steps towards larger shares of younger populations is still accruing or in early stages.
- Vaccination targets should be driven by an analysis of what is required to achieve certain goals and country specific targets need to account for local circumstances, including demographic and priority populations distribution. While many global goals have been expressed so far in terms of share of total population to be reached equally across all countries, this may yield an unintended vaccination strategies (such as vaccination of children) with uncertain benefits and possibly unintended use of scarce resources. This Strategy update argues for a move away from this approach.
- Mitigating future risks is important: uncertainties pose important risks. For instance, the potential for variants to emerge for which existing vaccines are poorly performing rendering them largely ineffective: the implication is that countries would have to reinstate control efforts already released and maintain those while reestablishing vaccine driven immunity. Another type of risk is linked to community continued acceptance of ongoing or return to public health and social measures of increased intensity as needed. While these unknowns are at play and evidence is being gathered, decisions are needed now on investments that will establish the opportunities of the near future. For instance, assuring global supply to potentially expand vaccination programmes in the near future is a ‘no regrets’ investment that allows greater specification of policy and programmatic refinements of its use over time.
- In light of all the above, thee options are proposed for the updated Global Vaccination Strategy covering the remaining of 2021 and 2022:
- A. An ambitious, no-regret ‘Universal global vaccination strategy’. This strategy would: i) Aim to mitigate future health risks for full global recovery, reaching the highest goal post on our conceptual goal framework; ii) prioritise highest risk groups where incremental benefits are largest, but encourage and support all countries to then quickly move to vaccinate all populations.
- B. An ‘All adult global vaccination strategy with risk mitigation’. This option would: i) Aim to reduce disease burden and putting countries on trajectory toward resuming socio-economic activity; ii) prioritise highest risk groups where incremental benefits are highest and encourage and support countries to reach 30+ or all adult populations. This strategy would advocate for important investments in vaccine supply and systems to ensure readiness once scientific uncertainty is cleared: for instance to expand immunization to all populations (including adolescent and children) should evidence become clear that this is needed; boost vaccination where evidence requires it.
- C. A, ‘Older adult global vaccination strategy’ focused effort. This option would: i) Reduce highest risk of mortality and protecting health systems limiting most sever public health and social measures needed for crisis response; ii) focus only on highest risk groups of 50+ where incremental benefits are highest, and encourage all countries to await for further evidence on need/desirability of further ambitions. This options risks leaving us unprepared should the need for more ambitious vaccination targets become evident as more data and knowledge is collected on scientific uncertainties.
Read the horrific rest for your self
EU GUIDELINES RELATING TO THE APPLICATION OF: THE COUNCIL DIRECTIVE 90/385/EEC ON ACTIVE IMPLANTABLE MEDICAL DEVICES
THE COUNCIL DIRECTIVE 93/42/EEC ON MEDICAL DEVICES – Guidance document – Scope, field of application, definition – Borderline products, drug-delivery products and medical devices incorporating, as integral part, an ancillary medicinal substance or an ancillary human blood derivative – MEDDEV 2.1/3 rev.3
https://ec.europa.eu/docsroom/documents/10328/attachments/1/translations/en/renditions/native
Commission proposes new measures for the better lifecycle management of medicine authorisations
The Commission has proposed to amend the variation legislation for medicines, to make the lifecycle management of medicines more efficient and better adapted to the modern context. The Regulation, which is part of the EU’s Pharmaceutical Strategy for Europe, adapts the current system for variations to marketing authorisations, to make it more efficient, reduce administrative burdens and better respond to scientific and technological advances.
https://ec.europa.eu/newsroom/sante/newsletter-archives/51544
blob:https://ec.europa.eu/747a737c-d903-4926-b636-2ede97c43bee
Regulation (EU) 2019/5 of the European Parliament and of the Council of 11 December 2018 amending Regulation (EC) No 726/2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency, Regulation (EC) No 1901/2006 on medicinal products for paediatric use and Directive 2001/83/EC on the Community code relating to medicinal products for human use (OJ L 4, 7.1.2019, p. 24, ELI: http://data.europa.eu/eli/reg/2019/5/oj).
Pharmaceutical cGMPS for the 21st Century — A Risk-Based Approach: Second Progress Report and Implementation Plan
Monitoring of COVID-19 medicines
The European Medicines Agency (EMA) makes use of real-world data to monitor the safety and effectiveness of authorised COVID-19 treatments and vaccines and other medicines used in patients with COVID-19 in the European Union (EU).
Human COVID-19 Medicines Pharmacovigilance Vaccines
EMA published the information on this page for use during the COVID-19 public health emergency. EMA is no longer updating this page.
COVID-19 vaccines: pharmacovigilance plan
The pharmacovigilance plan for COVID-19 vaccines sets out how EMA and the national competent authorities in the EU Member States identify and evaluate any new information that arises promptly, including any safety signals that are relevant for the benefit-risk balance of these vaccines:
Pharmacovigilance plan of the EU Regulatory Network for COVID-19 vaccines
First published:
13/11/2020
Reference Number:
EMA/333964/2020
English (EN) (161.32 KB – PDF)
For more information, see:
• COVID-19 vaccines: Monitoring vaccine safety and use in real life
• COVID-19 guidance: post-authorisation
Observational research
EMA is taking steps to use real-world data from clinical practice to monitor the safety and effectiveness of COVID-19 treatments and vaccines and other medicines used in patients with COVID-19.
Real-world monitoring complements EMA’s regular safety-monitoring activities, including spontaneous reporting of suspected side effects(link is external) by patients and healthcare professionals.
Information on ongoing COVID-19-related observational studies in the EU is available in the European Union electronic register of post-authorisation studies (EU PAS Register)(link is external). Users can find these studies by entering ‚COVID-19‘ in the ‚Title of Study‘ search filter.
EMA and the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) are encouraging all researchers to register their pharmacoepidemiological studies related to COVID-19 in the EU PAS Register.
They should also upload and make their study protocols public, with a description of the data collected, and include ‘COVID-19’ in the study title.
EMA has contracted institutions specialising in observational research to conduct several research projects detailed below.
Click on the research areas to read more about each project.
Safety monitoring of COVID-19 vaccines in the EU
Natural history of coagulopathy and use of anti-thrombotic agents in COVID-19 patients and COVID-19 vaccine recipients
Early safety monitoring of COVID-19 vaccines
Impact of COVID-19 infection and medicines in pregnancy
Building a framework for the conduct of multicentre cohort studies on the use of medicines in COVID-19 patients
Preparing an infrastructure for the monitoring of the coverage, safety and effectiveness of COVID-19 vaccines
For more information, see:
Report on pharmacovigilance tasks from EU Member States and the European Medicines Agency (EMA) 2019-2022
First published:
22/06/2023
Reference Number:
EMA/142695/2023
English (EN) (1.68 MB – PDF)
Related content
• COVID-19 guidance: post-authorisation
Related events
• Public stakeholder meeting on the approval and roll-out of COVID-19 vaccines in the EU (08/01/2021)
• Public stakeholder meeting on the approval and roll-out of COVID-19 vaccines in the EU (11/12/2020)
External links
• European Commission: Safe COVID-19 vaccines for Europeans(link is external)
Publications
• Considerations for pharmacoepidemiological analyses in the SARS-CoV-2 pandemic(link is external)
• Randomised controlled trials versus real world evidence: neither magic nor myth(link is external)
ema.europa outdated-pharmacovigilance-risk-assessment-committee-prac
1975
Products Liability–Doctrine of Unavoidably Unsafe Products Applied to Manufacturer of Polio Vaccine – Frank H. McCarthy
Follow this and additional works at: https://digitalcommons.law.utulsa.edu/tlr
Part of the Law Commons
Mistakes were not make!?
NFID Survey: Attitudes about Influenza and Pneumococcal Disease Prevention
Summary of Key Results
Attitudes and Practices Around Flu Vaccination
Overall, most US adults believe vaccination is the best protection against flu, but many do not plan to get vaccinated.
Here’s how the U.S. could release a COVID-19 vaccine before the election—and why that scares some
Science explains FDA’s emergency use authorization and other ways countries can speed approvals for vaccines to the new coronavirus
The FDA Knows that Pfizer’s mRNA Injections are Gene Editing Technologies
By falsely referring to injectable gene editing technologies as ‘vaccines’, Pfizer, the FDA and the NIH knowingly lied to the American people and global civilians. Make no mistake, this is criminal.
January 5, 2024: On January 3rd, Surgeon General Ladapo called for the stop of the use of COVID-19 mRNA ‘vaccine’ injections in human beings due to their potential to integrate foreign DNA into the human genome. Per the documents Pfizer submitted to the FDA, as well as the FDA’s and NIH’s own definitions of gene editing technologies, the FDA absolutely knew that Pfizer’s mRNA injections are gene editing technologies and not vaccines.
Bioelectronic Sensor Nodes for Internet of Bodies
Baibhab Chatterjee,1,2 Pedram Mohseni,3 and Shreyas Sen1
1Elmore Family School of Electrical and Computer Engineering, Purdue University, West Lafayette, IN 47907 USA and Center for Internet of Bodies (C-IoB), Purdue University, West Lafayette, IN 47907 USA;
email: bchatte@purdue.edu, shreyas@purdue.edu
2Department of Electrical and Computer Engineering, University of Florida, Gainesville, FL 32611 USA; email: chatterjee.b@ufl.edu
3Department of Electrical, Computer and Systems Engineering, Case Western Reserve University, Cleveland, OH 44106 USA and Institute for Smart, Secure, and Connected Systems (ISSACS), Case Western Reserve University, Cleveland, OH 44106 USA; email: pedram.mohseni@case.edu
https://arxiv.org/pdf/2212.11370.pdf
Inter-body coupling in electro-quasistatic human body communication: theory and analysis of security and interference properties
Inter-body coupling in Electro-quasistatic region: (a) Interference in received EQS-HBC signal due to inter-body coupling with other users. For multiple EQS-HBC users in close proximity, the received signal is usable only if the interference signal is a few dB lower than the signal. (b) While EQS-HBC devices restrict EM leakage within 10 cm of the user’s body, inter-body capacitive coupling can give rise to a new attack modality, where the attacker’s body is used to capacitively couple to the user’s body, and the coupled signal is picked up using an EQS-HBC receiver. (c) For devices that do not restrict EM leakage, such as Bluetooth or other WBAN devices, the signal can be picked up by an attacking device with an antenna within 5–10 m of the user. The human figures were created using the open-source software ‘MakeHuman’12.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902665/
The weaponization of artificial intelligence: What the public needs to be aware of
Technological progress has brought about the emergence of machines that have the capacity to take human lives without human control. These represent an unprecedented threat to humankind. This paper starts from the example of chemical weapons, now banned worldwide by the Geneva protocol, to illustrate how technological development initially aimed at the benefit of humankind has, ultimately, produced what is now called the “Weaponization of Artificial Intelligence (AI)”. Autonomous Weapon Systems (AWS) fail the so-called discrimination principle, yet, the wider public is largely unaware of this problem. Given that ongoing scientific research on AWS, performed in the military sector, is generally not made available to the public domain, many of the viewpoints on this subject, expressed across different media, invoke common sense rather than scientific evidence. Yet, the implications of a potential weaponization of our work as scientists, especially in the field of AI, are reaching further than some may think. The potential consequences of a deployment of AWS for citizen stakeholders are incommensurable, and it is time to raise awareness in the public domain of the kind of potential threats identified, and to encourage legal policies ensuring that these threats will not materialize.
Vaccine as a Platform (VaaP): Why the future of disease eradication needs to be data driven
As COVID-19 sweeps the world in 2020, it is interesting to note that the recent decade is termed the Decade of Vaccines (DoV) Collaboration [1]. The Global Vaccine Action Plan (GVAP)—endorsed by 194 Member States of the World Health Assembly—is a framework to prevent millions of deaths through more equitable access to existing vaccines for diverse communities by 2020.
GVAP, an unprecedented effort is the product of the DoV Collaboration. Numerous agencies are committed to achieving the goals of GVAP to stimulate discovery, development, and delivery of lifesaving vaccines. The plan is founded on the previous success of transforming how vaccines move from formulation to factory, families, and individuals.
In 2019, the WHO identified Vaccine Hesitancy (VH) as one of the top ten global health threats [2]. This is paradoxical because it occurred while access to data-centered technology detecting cancer driver-gene events specific to tumors and tissues of origin is becoming available [3].
2. Mass vaccination vs Person-Centric vaccination
Though the GVAP of 2011–2020 was an ambitious effort, it was not a “data-centric” approach [1]. Therefore, GVAP could never be “person-centric” in its execution.
At this juncture, in order of us to understand the term person centric, there is an opportunity to tap in to the wisdom of Peter F. Drucker. Widely considered to be the world’s and foremost pioneer of management theory, in his book, The Five Most Important Questions – You Will Ever Ask About Your Organization [15], Drucker prompts organizations to pose five questions. Through these purposeful questions, organizations are primed to act:
- What Is Our Mission?
- Who Is Our Customer?
- What Does the Customer Value?
- What Are Our Results?
- What Is Our Plan?
If we drill down into the details of these five questions, you will discover that there are not one or two individuals or groups but rather a network of inter-connected and distinct individuals. All with very distinct perspectives, objectives, values, beliefs, purpose, needs, strengths, limitations, vulnerabilities and everythng else, that makes them human. While there is an individual on both the supply side as well as the demand side of the vaccination process, the success of the vaccination process is dependent on all involved persons, without exceptions. From a marketing perspective, given that the demand side dictates the supply, in this context, we will focus on the specific perspective of the person, on the demand-side, the person receiving the vaccine, through the vaccination process. Whilst, acknowledging that the person(s) on the supply side are as important and critical, to the success of the vaccination goals but whose perspectives and objectives are different.
Specifically, in a “Mass Vaccination” process, numerous generalizations are made, pertaining to vaccine dispensation. Most of the generalizations are based on the target “herd” to be vaccinated. Some, generalizations could include age, ethnicity, and other demographic characteristics. However, certain precise information requirements are compromised. The focus on “the person” is compromised. Perhaps because of the perceived costs involved.
Thankfully, a “data-centric” approach on the other hand has the capabilities to narrow down a “herd” to a “person”, an individual. And this “person-centric” approach has the potential to create opportunities for precision. And this could potentially be a game changer for disease eradication. An example of such precision could include but not limited to the utilization of DNA data as a reference for necessary actions, more precisely addressing the very specific and precise needs of a specific individual. Simultaneously, on the supply side, other involved parties in the vaccination process also become important in the vaccine value chain. And, “who” needs “what” information, “when”, “where” and “how” are precisely understood, designed and orchestrated, so that every person in all the involved processes have the precise information needed to make the best possible decisions, in order to execute the best available action, for delivering the best possible outcome – a total eradication of a given disease.
In a very person-centric vaccination process, all involved parties benefit. In this panorama, the person receiving the vaccine benefits as well as persons who are accountable for delivering wider public health results. But, this can only be possible through the best use of all available data. Thus, in the digital age, to be data-centric is also to be person- centric. And this is true to any sector or industry.[4]
While there is little debate that vaccination is one of the greatest achievements of public health [5]and remains a widely accepted public health measure [6], a data-centric execution can reduce or eliminate VH. This point is made twofold, as the associated complexity in the vaccination process can only be addressed by a person-centric approach. Prior to the internet, there were no alternative options beyond a mass approach.
3. The Myopia: What business is vaccination in?
In 2012, the SAGE Working Group on Vaccine Hesitancy [7] was established. Its first task involved proposing a definition of Vaccine Hesitancy† and defining its scope to develop a model that categorized factors that influenced behavioral decisions in accepting vaccines.
†The group accomplished this through robust discussion of the use of the term that reviewed models of VH. This included: a commissioned systematic review of determinants of VH; field reports and personal observations from different organizations on hesitancy factors; and commissioned immunization managers’ survey of VH, and personal observations and experiences of Working Group members.
The working group presented their approach that focused on defining VH, its determinants, causes, expression, and impact. It also pursued the suggestion of indicator(s) of VH that could be used in monitoring progress within the DoV GVAP. Thus, organizational analysis and prioritizations based on identified strategies with their potential impact was performed. The role of WHO in addressing VH was outlined with specific roles of advisory committees [7].
While the approach focused on VH as the main issue, the Working Group was weakened by lacking a person-centric view of the problem. The focus was the vaccination process and execution rather than the vaccine consumer. At this juncture, one may compare the vaccine and the vaccination administration process through a lens of marketing scholarship that champions a product or service. Thus, new approaches to alleviate VH become clear.
One of the most influential ideas in marketing, introduced by Harvard Business School marketing professor Theodore Levitt, is marketing myopia—a nearsighted focus on selling products and services, rather than seeing the big picture of what consumers truly desire. An industry begins with the customer’s needs, not with a patent, raw material, or selling skill [8]. Levitt describes a lack of insight into what businesses do for their customers, effectively originating from the people who define the “why” of the product itself. Levitt cites an example of the train industry, arguing that railroad lines sharply declined because they saw themselves in the train business, rather than the transportation business. If leaders viewed themselves as helping customers travel, they could have expanded their business into other forms of transportation (buses or airplanes). Unfortunately, overlooking such potential allowed other companies to seize those opportunities and steal their lifeblood—passengers [9].
Medical sciences, broader healthcare, and public health industries are not immune from this same myopia. When troubled by the threat of VH, what are we threatened by? Its triumph in decreasing incidences of transmittable diseases, or by the loss of vaccines’ providing solutions for well-being? In Levitt’s words, “what business is the vaccine industry in?” One would hope they are in the business of “good health,” versus “vaccination.”
4. Lessons Learned–Data is key for success
The GVAP Review and Lessons Learned Reports confirm that VH presented major challenges during the past decade [10]. The report’s recommendation states the desire to “promote use of data to stimulate and guide action and to inform decision-making” [10]. This elaborates the next decades need for data collection; data-driven action; capacity to collect and use data; data transparency and sharing; flexibility to use data based on relative value; inclusion of qualitative data; integration with infectious disease surveillance data systems; preparing for transformative implementation of new technologies; collaborating with data scientists and informatics experts to ensure effective data use; and ensuring lessons are learned from Sustainable Development Goals and Universal Health Coverage/Primary Healthcare management strategies and data collection experiences [10].
When vaccines were first developed, data on vaccine failure was scarce, especially in vulnerable populations [11]. However, knowing the potential of applying data sciences, machine learning, or artificial intelligence, it’s plausible to better characterize vulnerable populations, which can be integrated to generate bioinformatic models for early identification of nonresponders. But, one non-biological risk persists–data non-use.
5. The disease of data non-use & the pursuit of wisdom
Data non-use poses even more risk than data misuse. It can be problematic with serious consequences [12]. The most effective initiatives to address specific contexts of data non-use include understanding the pertinent sources and reasons for data non-use to create appropriate incentives and repercussions; and awareness of multiple aspects underlaying this issue in other domains to keep benefits and limitations in perspective and move towards socially responsible reuse of data, thereby becoming the norm in saving lives and resources [12].
But what happens when people transform health and wellness experiences into data through tracking devices [13]? Our world is flooded with data from these devices—including those that log health data. Just as big data has the potential to rebuild America’s aging infrastructure [4], when sensor data is fully deployed to the frontlines, health data can meet the GVAP goals of the next decade. However, the health industry needs to embrace that health professionals cannot do this alone. Data comes from computers and from multiple sources . From a practitioner’s perspective, ALL the involved persons in the vaccination process, need to be able to answer ALL the specific questions posed, from all very specific individual perspectives – who, what, how, when, where and why. Only when these very specific personalized questions are answered in a very timely and accurate manner can we claim that our use of data has evolved.
In the case of the Immunization Information System (IIS)2 an expert system involved in administering vaccinations, it appears that it has not found its ‘why’ and this problem seems to manifest itself as the issue of vaccine hesitancy.
6. Vaccine as a Platform (VaaP)
The limited success in applying the IIS is partially due to capability limitations. Vaccinations as a social issue—including socio-techno-political-economic complexities—is best addressed from a “platform”3 viewpoint. Further scholarship is necessary to evaluate the IIS as a platform—Vaccine as a Platform (VaaP). This facilitates eliminating the myopia that Levitt identified. What’s certain: data must be understood as a capability and managed as such. Thus, a data strategy must be followed.
7. The data strategy for realizing VaaP
The data strategy blueprint [14] is a simple, strategy for decision makers to implement data use. It identifies data use as: data serves the purpose; data as a capability; and data as an asset. Fig. 1.
8. Conclusion: OMICs data & “Precision Vaccines”
Person-centric data is a key capability in VaaP, and critical factor for success for the GVAP. A potent idea that forms the basis for future development is predicting vaccine’s preventable disease with a great deal of precision [11] For this ambition to be fulfilled, we have OMICs data and its most recent success.
Combining OMICs data on vaccine immunity in groups with special vaccination needs, and screening and development, can increase knowledge on mechanisms of vaccine hyporesponsiveness. OMIC’s data can be used to design bioinformatic tools, predicting vaccination outcomes and providing genetic and molecular “signatures” of protective immune response. It may enable signature identification of vaccine safety, immunogenicity, and efficacy/protection, informing vaccine interventions in vulnerable populations [11].
This capability, when made available with the VaaP, could form future development and research in predicting vaccine preventable disease with precision vaccines, as a “one size fits all” intervention is impractical [6].
When such precision vaccines are delivered through a person-centric and data-driven vaccination process, a new societal solution unfolds. With the resulting elimination of data non-use, we may see the eradication of VH with the hope of adding to the list of eradicated diseases beyond small-pox.
The author attests meeting ICMJE criteria for authorship. There are no conflicts of interest to declare. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Recommended articles
References
- [1]WHO. Global vaccine action plan [2011–2020]. 2020. https://www.who.int/immunization/global_vaccine_action_plan/GVAP_doc_2011_2020/en [accessed 13 January 2020].Google Scholar
- [2]WHO. Ten threats to global health. 2019. https://www.who.int/emergencies/ten-threats-to-global-health-in-2019 [accessed 13 January 2020].Google Scholar
- [3]A. Calaprico, C. Olsen, M.H. Bailey, G.J. Odom, T.Terkelsen, T.C. Silva, et al.Interpreting pathways to discover cancer driver genes with MoonlightNat Commun, 11 (1) (2020), p. 69, 10.1038/s41467-019-13803-0 View PDF Google Scholar
- [4]Justhy DP. Scientific American [web blog]. How big data can help rebuild America’s aging infrastructure. 2017 January 17 – [cited 13 January 2020]. Available from: https://blogs.scientificamerican.com/observations/how-big-data-can-help-rebuild-americas-aging-infrastructure.Google Scholar
- [5]E. Dubé, C. Laberge, M. Guay, P. Bramadat, R. Roy, J. BettingerVaccine hesitancy: an overviewHum Vaccin, 9 (8) (2013), pp. 1763-1773, 10.4161/hv.24657View article View in ScopusGoogle Scholar
- [6]E. Dubé, D. Gagnona, N.E. MacDonaldSAGE Working Group on Vaccine Hesitancy. Strategies intended to address vaccine hesitancy: review of published reviewsVaccine, 33 (34) (2015), pp. 4191-4203, 10.1016/j.vaccine.2015.04.041View PDFView articleView in ScopusGoogle Scholar
- [7]WHO SAGE working group dealing with vaccine hesitancy. In: Strategies for addressing vaccine hesitancy – a systematic review. 2014. https://www.who.int/immunization/sage/sage_wg_vaccine_hesitancy_apr12/en[accessed January 13, 2020].Google Scholar
- [8]Levitt T. Marketing myopia. Harvard Business Review 2004 July 1;1–15. [accessed 22 January 2020]. https://store.hbr.org/product/marketing-myopia-hbr-bestseller/r0407l?sku=R0407L-PDF-ENG.Google Scholar
- [9]Gallo, A. A refresher on marketing myopia. Harvard Business Review [web blog]. 22 August 2016 – [accessed 13 January 2020]. Available from: https://hbr.org/2016/08/a-refresher-on-marketing-myopia.Google Scholar
- [10]WHO. Global vaccine action plan and decade of vaccines review and lessons learned reports. 2019. [accessed 13 January 2020]. https://www.who.int/immunization/global_vaccine_action_plan/GVAP_review_lessons_learned/en.Google Scholar
- [11]N. Cotugno, A. Ruggiero, V. Santilli, E. Concetta Manno, S. Rocca, S. Zicari, et al.OMIC technologies and vaccine development: from the identification of vulnerable individuals to the formulation of invulnerable vaccinesJ. Immunol. Res., 1–10 (2019), 10.1155/2019/8732191View article Google Scholar
- [12]K.H. Jones, L. Graeme, C. Stevens, D. Dobbs, D.V. Ford, N. Lea The other side of the coin: harm due to the non-use of health-related data Int. J. Med. Inform, 97 (2017), pp. 43-51, 10.1016/j.ijmedinf.2016.09.010View PDFView articleGoogle Scholar
- [13]G. Neff, D. Nafus Self-tracking MIT Press, Cambridge (2016)Google Scholar
- [14]D.P. Justhy The billion dollar byte: turn big data into good profits, the datapreneur way Morgan James Publishing, New York (2018)Google Scholar
- [15]P.F. Drucker The five most important questions you will ever ask about your organizationJohn Wiley & Sons (2011)Google Scholar
https://www.frontiersin.org/articles/10.3389/frai.2023.1154184/full#B19
JULIMINATION 
Hinterlasse einen Kommentar