Surrogate endpoints in global health research

Surrogate endpoints in global health research: still searching for killer apps and silver bullets?March 2018

In clinical research, there is widespread acceptance that surrogate endpoints may not translate to long-term benefits.

Clinical epidemiologists highlight the hazards of surrogate measures (eg, biomarkers, laboratory test results and short-term improvements in health) that substitute for outcomes which are important for patients (eg, avoiding premature death or severe disability).

For example, in cardiovascular research, improvements in parameters such as blood pressure or cholesterol may not improve outcomes such as deaths.  

Improvements in surrogate endpoints may not correlate with real outcomes of interest (and may even increase the risk of death, in some cases). And there are many examples and case studies in the literature that illustrate the hazards of using surrogates in clinical epidemiology

In comparison, in global health, we are often stunned when interventions that showed improvements in surrogate endpoints do not lead to lives being saved.

given the weak health systems in many low-income and middle-income countries, it is surprising that global health researchers and journalists have great expectations that new tools, widgets, drones and checklists will save lives and are then stunned and disappointed when they do not.

These ‘technological’ innovations often improve surrogate endpoints but may fail to meaningfully improve clinical outcomes in part because such outcomes improve only when a series of causal events are improved or completed.

Often, the entire cascade of events in healthcare needs to improve; merely improving one or two steps (eg, diagnosis or process of care) may not lead to improvements in overall outcomes or result in sustained benefit.

For example, while a patient’s health may not improve simply because they are able to consult their general practitioner via Skype, such innovations may make the process and experience of care more convenient, save the costs of travel and forfeited work and reduce care-seeking delays.

It is important that global health researchers are realistic when choosing indicators of effectiveness—an innovation designed to reduce costs or improve convenience should be evaluated primarily based on those indicators. 

We need to be more strategic about using surrogate endpoints in global health.

  • First, because some innovations are developed essentially to influence such surrogate endpoints;
  • second, because health system factors may predictably intervene in the care cascade and
  • third because waiting for long-term outcomes could delay the introduction of useful innovations

On the other hand, we must not use surrogate endpoints naively, given the dangers inherent in such endpoints. We must learn from clinical epidemiologists who argue that,

  • ‘researchers should avoid surrogate endpoints unless they have been validated’ and caution us that
  • the use of surrogate outcomes should be limited to situations where a surrogate has demonstrated robust ability to predict meaningful benefits’

Global health researchers should design innovative studies to show if and how surrogate endpoints alter subsequent causal events or influence patient outcomes.

RCTs may have little value in evaluating innovations such as the WHO Childbirth Checklist for which there is already strong and widely accepted evidence for the effectiveness of each of their component interventions.

Even if an RCT were to show improved maternal and neonatal outcomes in one setting, it is unclear that the intervention would have had a similar effect elsewhere, given that implementation and health system context vary significantly.

Indeed, causal pathways in public health interventions are often long and complex, and RCT results are subject to effect modification. 

Unfortunately, when such positive effects are found in RCTs, the result is often promoted as though the findings of the study would be applicable everywhere

We therefore propose two ways forward.

  1. First, map out the exact point in the cascade of care pathway in which an innovation is inserted and theorise how it may make a difference and what barriers may impede its effects on health outcomes.
  2. Second, use theory-driven heath systems and implementation research on the adoption of innovations to confirm or refute assumptions of how an innovation might work along the mapped-out care pathway and examine the impact of innovations on the surrogate endpoints along the care cascade.

We need to explicitly lower unreasonable expectations of the impact of innovations, when surrogate endpoints are used, and when findings (including of RCTs) may not be transferable beyond specific and similar context.

We need to explain the difference between surrogate endpoints and patient outcomes to policymakers and also to journalists to make sure their reporting is factual and honest.

New tools have their place and are urgently needed in global health. Searching for silver bullets and killer apps are worthwhile endeavours, but we must not expect them to be ‘silver’ or ‘killer’ when introduced into systems that are suboptimal.

If we care about making a real difference in global health, we also need to work on strengthening health systems to ensure holistic, effective and long-lasting solutions for patients and communities.

Original article: Surrogate endpoints in global health research

I found this use of meaningless, and even misleading, surrogate endpoints in almost all studies of opioids: Opioids Blamed for Side-Effects of Chronic Pain

3 thoughts on “Surrogate endpoints in global health research

  1. Kathy C

    Our Policy Makers are so out of touch, that explaining any of this, even by actual accredited Scientists, is virtually impossible. They tend to believe only what is hyped by our Media, or whatever cherry picked Industry funded “Science” Lobbyists present them with. These “Studies” are often presented as the last word, by a calculated and targeted Marketing and public relations machine.
    There is a bubble of misinformation around everything. The news about the Facebook Data, and the incredible violation of privacy, was not only to undermine our Democracy, even worse they did psychological experiments on the users. They sold the data from patient groups to industry interests, who cleverly undermined and infiltrated these groups. They were also able to monitor how well the health related, “News’ articles either went viral or lost people interest. That recent discussion of Doctor Beth Darnell’s Public Relations and marketing scheme, This was calculated misinformation, tied to the failure of the Opiate Guidelines. Coincidentally this biased “researcher” tied her Marketing to this Advertorial.


  2. Pingback: Those 2-Minute Walk Breaks? They Add Up | EDS and Chronic Pain News & Info

  3. Pingback: The Problem with Surrogate Endpoints | EDS and Chronic Pain News & Info

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