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Table 4 Solutions to PEARLES challenges encountered

From: Addressing challenges for clinical research responses to emerging epidemics and pandemics: a scoping review

Political and economic solutions identifiedChallenges encountered
Strengthen global collaborations and coalitions
  -Ensure global political awareness of infectious disease threats.
  -Strengthen collaborations between international organisations, national leaders, public, private and local stakeholders.
  -WHO to set out overarching research governance framework for research in outbreaks.
  -Integrate research in international outbreak response.
  -Ensure interventions are supported by all stakeholders, including national and local stakeholders.
  -Close collaboration between local and international researchers from research inception, tied to capacity building and be genuinely collaborative.
  -Research led by national teams.
  -Invest in national public health research institutes globally, targeting epidemic-prone regions.
Geopolitical
  -Ineffective global coordination and collaboration.
  -Research not integrated into national outbreak response.
  -Establishing outbreak as international concern may depend on the ability of LMICs to raise international interest.
  -Lack of compliance with WHO core capacities to detect, assess, report and respond.
  -Need for political approval.
  -Political unrest.
  -Research priorities dictated by funding bodies.
  -Lack of communication and engagement between stakeholders.
Funding
  -Establish dedicated funding sources in inter-epidemic times.
  -Establish international agreements on financial mechanisms for rapid release of funding and for addressing clinical trial liability coverage.
  -National governments to strengthen investments in preparedness and response.
  -Coordinate funding to ensure it is rapid and sufficient by using international coalitions and economies of scale.
  -Ensure sufficient, specific and flexible funding for research staff to avoid healthcare opportunity costs.
  -Explore industry funding to complement public funding.
  -Provide appropriate compensation for participation in research.
Funding
  -Insufficient funding resources.
  -Delays in identifying funding.
  -Weak funding mechanism and implementation for research in emergencies and neglected and tropical disease.
  -Funding not mobilisable at sufficient pace.
  -Limited national health budgets dedicated to research response efforts.
  -Opportunity costs and competing interests.
  -Over-reliance on unpaid staff doing research in addition to normal duties, with risk to care, staff and research.
Health systems and infrastructure
  -Strengthen health systems and research capacity.
  -Strengthen supporting infrastructure, targeting regions vulnerable to epidemics.
  -Expand critical care resources.
  -Develop clinical research facilities in predicted ‘hot spot’ regions.
Health systems and infrastructure
  -Limited healthcare systems.
  -Limited supporting infrastructure, electricity and water supply and technical resources.
  -Lack of national health research institutes.
  -Competing interests of resources.
Administrative, regulatory and logistic solutions identifiedChallenges encountered
Human resources and research capacity
  -Ensure capacity to respond to outbreaks across departments, particularly in predictable epidemic-prone regions.
  -Ensure sufficient support for ethics review boards.
  -Identify and utilise existing skills and talents, re-deploy existing research staff.
  -Fund dedicated study teams to avoid additional burden on other staff.
  -Ensure adequate, sustained research training for staff, particularly during stable periods.
  -Establish clinical research networks that are incentivised and prepared to respond to outbreaks and politically supported.
  -Form research response teams, with dedicated research coordinators.
  -Recruit additional staff from outside of the epidemic area to reduce strain.
  -Set up mobile research teams to reach large areas.
  -Improve staff perception of research as a core role of healthcare professionals.
Human resources and research capacity
  -Limited number of staff.
  -Risk of already scarce staff becoming overwhelmed and additional burden of research activities across services.
  -Training of staff in research not seen as a priority.
  -Lack of research coordinators.
  -Increased workload from study protocol risk negatively affecting patient care.
  -Difficulties in deploying staff internationally sufficiently rapidly in the context of an outbreak.
Communication
  -Establish direct stakeholder communication channels.
  -Develop harmonised, coordinated communication activities with shared oversight structures and joint management.
  -Establish detailed communication and dissemination plans and templates.
  -Provide continuous updates on research activity to stakeholders as appropriate through a variety of channels.
  -Set up ‘pandemic champions’ to establish links with sites, to facilitate coordination and to raise awareness.
Communication
  -Data stored in countries other than that affected, disempowers the national team.
  -LMICs unable to access trial results after the study is completed.
  -Challenges for LMICs to gain international interest from study results.
  -Challenging to control the interpretation of research output by the media and political leaders.
Frameworks
  -Establish a normative framework for research and development.
  -Create frameworks and governance charts for clear decision-making procedures, standard operational procedures and administrative infrastructures.
  -Prioritise research questions, pre-design study protocols and training materials in advance, ready to be deployed.
Frameworks
  -Lengthy process of planning, formalising and gaining approval of study protocol.
  -Lack of integrated standards for data collection and infrastructure for data sharing.
  -Delays in obtaining inter-institutional data sharing agreements.
  -Time lag for distant reference lab results.
  -No apparent benefit to those affected to share data.
  -Delayed data sharing due to academic competition culture.
Data and sample sharing
  -International agencies (e.g. WHO) to establish international data sharing frameworks.
  -Refinement of international agreements, such as the Declaration of Helsinki to include instructions on how to handle benefit sharing for sponsor and host countries.
  -Develop templates and platforms for data and sample sharing.
  -Enhance the value of research output dissemination to all stakeholders through long-term collaboration and health system improvements.
  -Funding approvals to incorporate agreement on data dissemination.
  -Establish data sharing ahead of emergencies.
  -Develop a mechanism to manage intellectual property and data governance.
  -Establish standard to reduce uncredited secondary analysis to facilitate data sharing.
  -Ensure global sharing of data with fair distribution.
  -Enhance the value of the research to each beneficiary through fair dissemination of knowledge, product development, long-term research collaboration, and/or health system improvements.
Data and sample sharing
  -Data collection and sharing on paper records sometimes not possible due to infection control and confidentiality issues.
  -Loss of control and ownership of data following dissemination.
  -Data not made available during outbreaks and long delays in publishing data after outbreaks.
  -Issues around maintaining participant confidentiality when sharing data.
  -Lack of control of communication.
  -Confidentiality requirements imposed by commercial entities.
Publication standards
  -Agree open data sharing and publication standards.
  -A shift in paradigm to a common goal of data sharing rather than publication.
  -Ensure pre-prints of novel data are available prior to publication.
  -Develop and use an ‘emergency research pledge’ by journals.
  -Ensure researchers, including local collaborators, are credited for their work.
Traditional publication process
  -Traditional journal review processes are too slow to inform emergency outbreak response strategies.
  -Publication authorship imbalances.
Pathways for regulatory and ethics approvals
  -Establish accelerated regulatory pathways and expedited ethical review processes for emergencies.
  -Establish institutional review boards in epidemic ‘hot spot’ regions.
  -Enable single portals for applications.
  -Establish joint ethics review committees.
  -Enable parallel submission of ethical, financial and scientific approvals.
  -Develop pre-approved study protocols with agreed acceptable study design modifications.
  -Develop pre-approved site agreements, between multiple sites and organisations, in geographically strategic regions.
  -Consideration of the management of bio-samples should be part of the ethical and protocol review.
Pathways for regulatory and ethics approvals
-Delays caused by existing ethical frameworks.
  -Complex ethic committee forms and inconsistencies between forms.
  -Variation in REB responses to the same study.
  -Lack of framework to fast-track vaccine trials or drug testing.
  -Existing frameworks not fit for emergency research.
  -Lengthy time taken to gain research approvals during epidemics and pandemics.
  -Requirement of approval from multiple entities (including political) and variations between countries.
  -Reluctance from national officials to approve trials.
Drug and vaccine licencing and access
  -Form Joint Scientific Advisory and Data Safety Review Committees for all studies linked to a specific intervention or group of interventions.
  -Global regulatory agencies should collaborate to ensure accelerated licensure strategy.
  -Contracts with multiple manufacturing and distribution units to improve resilience in the supply of medicines to participating trial site.
  -Primary role of authorising use of investigational vaccines and drugs should be given to the affected countries.
Drug and vaccine licencing and access
  -Length of time for drugs and vaccines to be approved.
  -Lack of framework to fast-track vaccine trials and drug testing.
Research support systems
  -Provide sufficient funds for the renovation of study facilities and provide supportive infrastructure.
  -Strengthen satellite and wireless internet access in epidemic-prone regions.
  -Use existing infrastructure, e.g. from other disease programmes.
  -Set up logistical support platforms.
  -Ensure flexible solutions that can be readily adaptable depending on the context.
Research support systems
  -Rudimentary and overwhelmed healthcare facilities.
  -Technical resource limitations.
  -Limited access to freezer storage facilities.
  -Difficulty reaching remote field sites.
  -Lack of effective personal protective equipment
  -Poor safety for staff and participants.
Ethical and social solutions identifiedChallenges encountered
Standards
  -Develop standards for the conduct of research in emergencies, including frameworks for the inclusion of vulnerable groups and appropriate study designs.
  -Ensure equitable access to best available evidence-based care for all patients, regardless of consent to participate.
  -Ensure appropriate compensation for participation in research.
Standards
  -Lack of uniform standards for research ethics committees.
  -Lack of international consensus about research groups’ obligations to provide trial participants health benefits.
  -Non-transparent ethical approval processes.
  -Exclusion of pregnant women and children from trials.
  -Expedited review might pose a risk to patients.
  -Research perceived as the only way to access care/treatment.
  -Lack of agreement on appropriate study designs for emergencies.
Consent methods
  -Evaluate alternative consent methods proposed during emergencies.
  -Ensure consent methods are culturally appropriate.
Consent methods
  -Obtaining complex informed consent, from severely ill patients and from relatives.
  -Verbal proxy consent contested at later date.
Community engagement
  -Invest in community engagement from inception.
  -Explore outbreak and community context, and use the findings to inform the study design, set-up, delivery and dissemination.
  -Ensure protocol and consent forms are consistent with community values and internationally accepted ethical principles.
  -Build trust through understanding and respect of different cultures.
  -Ensure study design meets cultural needs.
  -Manage expectations of all stakeholders.
  -Facilitate community empowerment.
  -Provide outreach community information sessions.
  -Establish community advisory boards.
  -Use social messaging and informational materials to improve the knowledge and perception of the study and disease and to address rumours.
  -Ensure effective consultation and communication with affected or at-risk communities, for example, through community liaison teams.
  -Involve social scientists and medical anthropologists to help understand the concerns and needs of the community.
  -Translate social science research into practice.
  -Facilitate relationships between groups with cultural differences.
Community engagement
  -Mistrust, suspicion and rumours around clinical trials, national and international response, sometimes due to local media and other sources.
  -Poor understanding of how to address rumours.
  -Fear of the disease.
  -Cultural perceptions of tissue and blood sampling.
  -Poor understanding of how to respect different cultures.
  -Lack of community engagement and poor perception of power dynamics.
  -Perception of research being unfair.