Evidence-based decision-making has become a global standard for health interventions, policy, and programs. In the human immunodeficiency virus (HIV) arena, this methodology has been a welcome trend. While randomized controlled trials (RCTs) with HIV endpoints are encouraged for public health interventions, there are limitations with using RCT as the gold standard of evidence for HIV interventions.1–3
These limitations include the very high cost of efficacy trials, the relative scarcity of populations with sufficient incidence in which to mount trials, and the ethical imperative to compare experimental treatments with ever more potent control conditions, which can mitigate the ability to assess efficacy. In addition, some interventions have never been formally evaluated with RCTs but have demonstrated significant impact from implementation and observational research, making RCTs now either unfeasible or ethically challenging. An example of this limitation is the use of needle and syringe exchange programs for injecting drug users (IDUs), for which many would argue the window of opportunity to conduct an RCT has long passed.4
Within the realm of clinical medicine, evidence-based medicine (EBM) is now considered the basis by which to define standards of clinical care. Defining packages of clinical services has been predicated on systematic reviews of individually randomized double-blinded placebo-controlled trials of medications and/or services for patients with varying clinical conditions. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system has been widely endorsed as the most effective method with which to grade the current state of evidence for a variety of clinical interventions.5,6
The GRADE system was designed for individual-level clinical interventions in which the traditional hierarchy of evidence is applied. Specifically, the highest-quality evidence is derived from double-blinded placebo-controlled RCTs, followed by unblinded RCTs, prospective cohort studies, case-control studies, clinical case series, and consensus among experts. Additional weight is given to appropriately executed systematic reviews and meta-analyses of studies with little heterogeneity among participants, methods, and results.
To further standardize the presentation of evidence in clinical interventions and meta-analyses, criteria including the Consolidated Standards of Reporting Trials (CONSORT) and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were developed, which have facilitated the grading of evidence.7,8
Given the nature of individual-level clinical interventions, the GRADE system has facilitated the development of clinical practice guidelines and other clinical practice tools to promote the practice of EBM.9
The GRADE system is also relevant, as it integrates the potential for a separation between quality of evidence and strength of recommendations based on extenuating circumstances, such as cost-efficacy, risk-benefit, and contextual factors.10
While there is general acceptance of the use of the GRADE system in clinical medicine, there has been no widely accepted standard for grading public health interventions, although a series of different algorithms and hierarchies of evidence have been proposed.1,11–13
Varying algorithms of evaluating public health interventions are also in use by the International Agency for Research on Cancer, the United States Preventive Services Task Force (USPSTF), the newly revived Canadian Task Force on Preventive Health Care (CTFPHC), and the National Institute for Health and Clinical Excellence in the United Kingdom, among others. While Hill's criteria for causality, including strength of the relationship, dose-response, temporality, experimental evidence, analogy, and biologic plausibility, still apply to public health interventions, it is more difficult to demonstrate efficacy using traditional evaluation strategies.14
One reason for this difficulty is that public health interventions tend to be context-specific, including geographic and socioeconomic contexts, and are generally multifaceted. Moreover, primary prevention strategies targeting at-risk populations may be subject to the prevention paradox first described by Rose.15
The prevention paradox describes a situation in which an effective population-level public health intervention may provide only little benefit at the individual level while being significant at the population level, thereby complicating the measurement of effectiveness or efficacy.16
There is an emerging awareness of the significant roles the key or most-at-risk populations (MARPS) may play in HIV epidemics. Many country epidemics began as concentrated epidemics among MARPS including gay men and other men who have sex men (MSM), sex workers, and IDUs, and then transitioned to more generalized epidemics. The role of MARPS in concentrated epidemics is relatively uncontroversial. However, in generalized epidemic settings, the initial presentation of numerous HIV epidemics was among MSM.3,4
With the emergence of generalized epidemics, the role of these three MARPS and other country-specific MARPS, such as truckers, internally displaced people, and victims of gender-based violence, has been given less attention. However, there is a growing evidence base of disproportionate risk among MARPS including sex workers, MSM, and IDUs in these settings.17,18
Recent assessments of global HIV prevention suggest that few HIV/acquired immunodeficiency syndrome (AIDS) prevention, treatment, and care programs include targeted programming for these populations.19
Given this lack of funding, infections continue to increase in the context of slowing epidemics in the general population and, with the exception of IDUs, there has been limited progress in defining the optimal package of services for MARPS in low- and middle-income settings.
In response to this lack of progress, our multi-disciplinary team worked to develop a novel system of evaluating evidence for HIV interventions targeting decreasing HIV risk specifically among MSM. We propose the use of the term the “Highest Attainable Standard of Evidence” (HASTE). HASTE was initially used to define a package of services for preventing HIV infection among MSM in low- and middle-income countries (LMIC). Other derivatives of the GRADE system have been suggested, including by Tang et al.13
When stigma affecting MARPS is compounded with the difficulties and limitations of RCTs evaluating public health intervention with biological endpoints, the evidence base for any HIV intervention supporting these vulnerable populations is limited. Thus, while our initial intent was to use the GRADE methodology to evaluate individual interventions, it became clear that the system required modifications to include assessment of what we termed HASTE. HASTE deliberately echoes the language of human rights conventions on the right to health, which accept that what can realistically be attained in resource-constrained environments can still serve as life-saving aspirational goals.20,21
The aspiration was to develop a system that balances scientific integrity with the need to make recommendations for prevention programming and policies for an understudied and underserved population.