Trials Of Public Health Interventions Research Articles

The Ethical Obligation for Research During Public Health Emergencies: Insights From the COVID-19 Pandemic

In times of crises, public health leaders may claim that trials of public health interventions are unethical. One reason for this claim can be that equipoise—i.e. a situation of uncertainty and/or disagreement among experts about the evidence regarding an intervention—has been disturbed by a change of collective expert views. Some might claim that equipoise is disturbed if the majority of experts believe that emergency public health interventions are likely to be more beneficial than harmful. However, such beliefs are not always justified: where high quality research has not been conducted, there is often considerable residual uncertainty about whether interventions offer net benefits. In this essay we argue that high-quality research, namely by means of well-designed randomized trials, is ethically obligatory before, during, and after implementing policies in public health emergencies (PHEs). We contend that this standard applies to both pharmaceutical and non-pharmaceutical interventions, and we elaborate an account of equipoise that captures key features of debates in the recent pandemic. We build our case by analyzing research strategies employed during the COVID-19 pandemic regarding drugs, vaccines, and non-pharmaceutical interventions; and by providing responses to possible objections. Finally, we propose a public health policy reform: whenever a policy implemented during a PHE is not grounded in high-quality evidence that expected benefits outweigh harms, there should be a planned approach to generate high-quality evidence, with review of emerging data at preset time points. These preset timepoints guarantee that policymakers pause to review emerging evidence and consider ceasing ineffective or even harmful policies, thereby improving transparency and accountability, as well as permitting the redirection of resources to more effective or beneficial interventions.

Leveraging technology to personalize cognitive enhancement methods in aging.

As population aging advances at an increasing rate, efforts to help people maintain or improve cognitive function late in life are critical. Although some studies have shown promise, the question of whether cognitive training is an effective tool for improving general cognitive ability remains incompletely explored, and study results to date have been inconsistent. Most approaches to cognitive enhancement in older adults have taken a 'one size fits all' tack, as opposed to tailoring interventions to the specific needs of individuals. In this Perspective, we argue that modern technology has the potential to enable large-scale trials of public health interventions to enhance cognition in older adults in a personalized manner. Technology-based cognitive interventions that rely on closed-loop systems can be tailored to individuals in real time and have the potential for global testing, extending their reach to large and diverse populations of older adults. We propose that the future of cognitive enhancement in older adults will rely on harnessing new technologies in scientifically informed ways.

Comparison of registered and published intervention fidelity assessment in cluster randomised trials of public health interventions in low- and middle-income countries: systematic review

BackgroundCluster randomised trials (CRTs) are a key instrument to evaluate public health interventions. Fidelity assessment examines study processes to gauge whether an intervention was delivered as initially planned. Evaluation of implementation fidelity (IF) is required to establish whether the measured effects of a trial are due to the intervention itself and may be particularly important for CRTs of complex interventions conducted in low- and middle-income countries (LMICs). However, current CRT reporting guidelines offer no guidance on IF assessment. The objective of this review was to study current practices concerning the assessment of IF in CRTs of public health interventions in LMICs.MethodsCRTs of public health interventions in LMICs that planned or reported IF assessment in either the trial protocol or the main trial report were included. The MEDLINE/PubMed, CINAHL and EMBASE databases were queried from January 2012 to May 2016. To ensure availability of a study protocol, CRTs reporting a registration number in the abstract were included. Relevant data were extracted from each study protocol and trial report by two researchers using a predefined screening sheet. Risk of bias for individual studies was assessed.ResultsWe identified 90 CRTs of public health interventions in LMICs with a study protocol in a publicly available trial registry published from January 2012 to May 2016. Among these 90 studies, 25 (28%) did not plan or report assessing IF; the remaining 65 studies (72%) addressed at least one IF dimension. IF assessment was planned in 40% (36/90) of trial protocols and reported in 71.1% (64/90) of trial reports. The proportion of overall agreement between the trial protocol and trial report concerning occurrence of IF assessment was 66.7% (60/90). Most studies had low to moderate risk of bias.ConclusionsIF assessment is not currently a systematic practice in CRTs of public health interventions carried out in LMICs. In the absence of IF assessment, it may be difficult to determine if CRT results are due to the intervention design, to its implementation, or to unknown or external factors that may influence results. CRT reporting guidelines should promote IF assessment.Trial RegistrationProtocol published and available at: https://doi.org/10.1186/s13643-016-0351-0

Trials and tribulations: cross-learning from the practices of epidemiologists and economists in the evaluation of public health interventions.

The randomized controlled trial is commonly used by both epidemiologists and economists to test the effectiveness of public health interventions. Yet we have noticed differences in practice between the two disciplines. In this article, we propose that there are some underlying differences between the disciplines in the way trials are used, how they are conducted and how results from trials are reported and disseminated. We hypothesize that evidence-based public health could be strengthened by understanding these differences, harvesting best-practice across the disciplines and breaking down communication barriers between economists and epidemiologists who conduct trials of public health interventions.

Comparison of registered and published intervention fidelity assessment in cluster randomised trials of public health interventions in low- and middle-income countries: systematic review protocol.

BackgroundCluster randomised trials (CRTs) are a key instrument to evaluate public health interventions, particularly in low- and middle-income countries (LMICs). Fidelity assessment examines study processes to gauge whether an intervention was delivered as initially planned. Evaluation of implementation fidelity (IF) is required to establish whether the measured effects of a trial are due to the intervention itself and may be particularly important for CRTs of complex interventions. Current CRT reporting guidelines offer no guidance on IF assessment. We will systematically review the scientific literature to study current practices concerning the assessment of IF in CRTs of public health interventions in LMICs.MethodsWe will include CRTs of public health interventions in LMICs that planned or assessed IF in either the trial protocol or the main trial report (or an associated document). Search strategies use Medical Subject Headings (MESH) and text words related to CRTs, developing countries, and public health interventions. The electronic database search was developed first for MEDLINE and adapted for the following databases: EMBASE, CINAHL, PubMed, and EMB Reviews, to identify CRT reports in English, Spanish, or French published on or after January 1, 2012. To ensure availability of a study protocol, we will include CRTs reporting a registration number in the abstract. For each included study, we will compare planned versus reported assessment of IF, and consider the dimensions of IF studied, and data collection methods used to evaluate each dimension. Data will be synthesised using quantitative and narrative techniques. Risk of bias for individual studies will be assessed using the Cochrane Collaboration Risk of Bias Tool criteria and additional criteria related to CRT methods. We will investigate possible sources of heterogeneity by performing subgroup analysis. This review was not eligible for inclusion in the PROSPERO registry.DiscussionFidelity assessment may be a key tool for making studies more reliable, internally valid, and externally generalizable. This review will provide a portrait of current practices related to the assessment of intervention fidelity in CRTs and offer suggestions for improvement. Results will be relevant to researchers, those who finance health interventions, and for decision-makers who seek the best evidence on public health interventions.Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-016-0351-0) contains supplementary material, which is available to authorized users.

Collecting and analysing cost data for complex public health trials: reflections on practice

BackgroundCurrent guidelines for the conduct of cost-effectiveness analysis (CEA) are mainly applicable to facility-based interventions in high-income settings. Differences in the unit of analysis and the high cost of data collection can make these guidelines challenging to follow within public health trials in low- and middle- income settings.ObjectiveThis paper reflects on the challenges experienced within our own work and proposes solutions that may be useful to others attempting to collect, analyse, and compare cost data between public health research sites in low- and middle-income countries.DesignWe describe the generally accepted methods (norms) for collecting and analysing cost data in a single-site trial from the provider perspective. We then describe our own experience applying these methods within eight comparable cluster randomised, controlled, trials. We describe the strategies used to maximise adherence to the norm, highlight ways in which we deviated from the norm, and reflect on the learning and limitations that resulted.ResultsWhen the expenses incurred by a number of small research sites are used to estimate the cost-effectiveness of delivering an intervention on a national scale, then deciding which expenses constitute ‘start-up’ costs will be a nontrivial decision that may differ among sites. Similarly, the decision to include or exclude research or monitoring and evaluation costs can have a significant impact on the findings. We separated out research costs and argued that monitoring and evaluation costs should be reported as part of the total trial cost. The human resource constraints that we experienced are also likely to be common to other trials. As we did not have an economist in each site, we collaborated with key personnel at each site who were trained to use a standardised cost collection tool. This approach both accommodated our resource constraints and served as a knowledge sharing and capacity building process within the research teams.ConclusionsGiven the practical reality of conducting randomised, controlled trials of public health interventions in low- and middle- income countries, it is not always possible to adhere to prescribed guidelines for the analysis of cost effectiveness. Compromises are frequently required as researchers seek a pragmatic balance between rigor and feasibility. There is no single solution to this tension but researchers are encouraged to be mindful of the limitations that accompany compromise, whilst being reassured that meaningful analyses can still be conducted with the resulting data.

Public health economics of body and mind: a health economist's perspective

BackgroundIf public health is the science and art of how society collectively aims to improve health, and reduce inequalities in health, then public health economics is the science and art of how we choose to do this with limited resources. The spectrum of public health activities is broad; for example, environmental policy, infectious disease control, individual behaviour change, and informing government legislation. I draw together key methodological considerations for the design, undertaking, and analysis of economic assessment alongside trials of public health interventions spanning environmental change and behaviour change relating to the body and mind. The discipline of health economics has grown up alongside a medical model of health. Many public health practitioners and health economists interested in public health are realising that emphasis is shifting from traditional behaviour-change interventions towards interventions that aim to change physical environments and social norms and that might need government legislation. This shift means that health economists need to approach the economic assessment of the broad spectrum of public health interventions in a more creative way. Quality-adjusted life-years may not fully capture diverse benefits of public health interventions but are useful for benchmarking the cost effectiveness of public health against clinical services. Health economists who have focussed on notions of efficiency need now to think more about equity, in view of public health goals of reducing inequalities in health. The aim is to convey to a public health science audience the challenges and opportunities facing health economists interested in public health today. MethodsI show these challenges and suggest solutions by drawing on recent published and ongoing trials of public health interventions with a health economics component. Changing the environment was investigated in the CHARISMA trial by improvement of heating and ventilation in homes of children with asthma. Changing individual physical behaviour was investigated by assessment of a national exercise referral scheme in the NERS trial. Changing individual mental behaviour was assessed by bringing mindfulness into the workplace in the Gwynedd trial. FindingsEmerging lessons include (1) the need to think about how evidence of cost effectiveness is going to be used by government and local commissioners of services, within what time horizon, and what the expected interplay may be between stakeholders; (2) mounting evidence that the government needs to focus on altering physical environments (eg, local planning laws, speed limits) and social environments (eg, school and workplace culture); and (3) a readiness to recognise where behaviour change has proved successful in the commercial sector, delivered in groups or online (eg, Slimming World). These three examples of economic analysis highlight thinking on design of economic assessment, power calculation issues relating to economic analysis, micro-costing techniques, and choice and range of outcome measures. InterpretationFaced with real public health challenges, we are beginning to learn how to design, undertake, and analyse economic assessments of public health interventions. We are learning how to provide clear evidence-based information to policy makers. Concrete recommendations to ensure funding streams for health economists, such as through the public health research programme, will help to support a methodological advancement in this field. FundingPublic Health Wales.

Sample size calculation in trials of public health interventions: a discussion of implications for health economists

BackgroundStatistical analysis enables ascertainment of whether or not there are interesting differences in effects between two or more groups and allows inferences to be made about the population from which a sample comes. For those of us interested in these differences, to be able to report on their statistical significance is useful to help us remark on the confidence we have in our results. However, careful consideration should be given to the choice of sample size. We investigated recent developments in the methodological considerations surrounding issues of identification of an appropriate sample size for a study, investigating first the issue in the context of clinical trials before going on to discuss the issue in terms of public health. MethodsIn this discussion piece, we highlight recent developments in the area of sample size calculation. We then offer two case studies that provide examples of sample size estimation under different scenarios: when no power or sample size calculations have been mentioned and when power or sample size calculations have been done properly. The first was done by the UK prospective diabetes study group (1998) in which the sample size was 1148, although there was no explicit mention of how this sample size was calculated. The second case study was an example by Briggs and Gray (1998) on the study of intracranial aneurysms. They plotted the sample size requirements as a function of the maximum cost-effectiveness ratio. One can then, for a given level of cost effectiveness, work out the sample size needed for different levels of power. FindingsAlthough clinical trials calculate sample sizes on the basis of clinical outcomes, we show that these sample sizes might not provide enough power for any economic assessment we might want to undertake, because economic assessments deal with both costs and treatment effects. Usually, economic assessment relates to estimation rather than hypothesis testing. Therefore, calculations of power and sample size in economic assessment are done in relation to some value of maximum willingness to pay (WTP) for a unit of treatment effect. The upper confidence limit of the incremental cost-effectiveness ratio of a cost-effective treatment must fall below the value of the maximum WTP and the sample size must provide enough power for this to be possible. Further, in economic assessment of public health interventions, the effective sample size might be less than the actual sample size used because of intra-cluster correlation and so the sample size must be corrected for this factor. InterpretationWe argue that a systematic review of the published work is needed to highlight the state of play with regard to sample size estimation, especially in economic assessment of public health interventions. By methodically collating the available evidence, the case for best practice in choosing the appropriate sample size can be put forward and progress can be made in increasing the number of studies that are sufficiently powered. FundingNone.

Pragmatic trials of non-NHS interventions: experiences from a Randomised Controlled Trial of the Strengthening Families 10-14 UK Programme (SFP10-14 UK)

Background: Pragmatic trials of public health interventions outside the NHS are relatively scarce, much needed and face particular challenges. These include funding, of intervention costs in particular; trial implementation in professional and organisational cultures unused to randomised trial procedures, including randomisation, maintaining the counterfactual, recruitment; and relevance of findings for and translation into policy and practice. Objectives: The current NPRI funded trial of SFP 10-14 UK is presented as a case study to discuss these issues, solutions and remaining barriers. The SFP 10-14 UK programme aims to strengthen areas of family life that protect against substance misuse, for example, parenting, communication, and young people’s resilience skills. The SFP 10-14 UK is being delivered by statutory and voluntary agencies in six local authority areas across Wales, and is offered to mixed groups comprised of families from the general population, and families who may experience/present challenges within a group setting. Methods: The trial aims to recruit 748 families, 374 of whom will be randomised to receive the usual services available to families within their local area. 374 families will receive the SFP 10-14 UK in addition to usual care. Families are identified by staff employed within the statutory services and voluntary sectors and referred to embedded research staff for recruitment. Results: Challenges encountered related to a lack of awareness of the randomised trial as a research paradigm among staff and key referring agencies, related concerns about the ethics of randomisation and the maintenance of the counterfactual among the usual care group, and challenges regarding the maintenance of recruitment and intervention fidelity. Whilst a challenge in itself, partnership working with delivery agencies, programme trainers, and the Welsh Assembly Government at all stages of the development, funding and conduct of the trial has proved an important strategy to overcome these issues. Conclusions: This trial seeks to generate evidence on the effectiveness and cost effectiveness of the SFP10-14 UK which is of direct relevance to policy makers, commissioners and practitioners. The trial highlights that strategic partnership working, the winning of ‘hearts and minds’ regarding the ethics and operationalisation of randomisation, and maintaining the balance between internal and external validity are key areas of focus for the successful conduct of pragmatic trials in non-NHS settings. The lessons learnt from its implementation will be important for future multi-sector/agency policy trials and for role out of the intervention if found to be efficacious.

Reporting Implementation in Randomized Trials: Proposed Additions to the Consolidated Standards of Reporting Trials Statement

Randomized controlled trials of public health interventions are often complex: practitioners may not deliver interventions as researchers intended, participants may not initiate interventions and may not behave as expected, and interventions and their effects may vary with environmental and social context. Reports of randomized controlled trials can be misleading when they omit information about the implementation of interventions, yet such data are frequently absent in trial reports, even in journals that endorse current reporting guidelines. Particularly for complex interventions, the Consolidated Standards of Reporting Trials (CONSORT) statement does not include all types of information needed to understand the results of randomized controlled trials. CONSORT should be expanded to include more information about the implementation of interventions in all trial arms.

Controversies in the public health approach to keratinocyte carcinomas

Keratinocyte carcinomas are very common cancers in fair-skinned populations throughout the world. The term 'keratinocyte carcinoma' includes basal and squamous cell carcinoma of the skin, but not other cancers that may be included under the more ambiguous term 'nonmelanoma skin cancer'. Incidence and mortality are important for assessing impact and recent research suggests that these cancers are increasing in incidence in young adults. There is evidence to suggest that this trend may be due, in part, to the popularity of ultraviolet exposures in commercial tanning facilities. Mortality from keratinocyte carcinoma reveals distinct patterns suggestive of an important role of human papilloma virus infection. Ultimately, our aim is to reduce mortality and morbidity from these cancers, and to that end several large-scale trials of public health interventions have been conducted that may help point the way forward.