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A new study, led by researchers at the Infectious Diseases Data Observatory (IDDO) and the Mahidol Oxford Tropical Medicine Research Unit (MORU) at NDM, found that a large number of national guidelines recommend at least one treatment proven not to work.

Ward in Madagascar © World Bank

National clinical guidelines for the treatment of COVID-19 vary significantly around the world, with under-resourced countries the most likely to diverge from World Health Organisation (WHO) treatment recommendations, finds a new publication in the journal BMJ Global Health.

Professor Philippe Guerin, Director of IDDO and one of the study leads, said: ‘There is clearly more variation in national guidelines for COVID-19 therapeutics than there should be to ensure optimum treatment. In the fog of war on COVID-19, countries clearly felt the need to do something, even if it was based on very little evidence, and the WHO treatment guidelines were not systematically used and disseminated. But why many of these unproven remedies continued to be recommended as evidence of their ineffectiveness accrued is much less clear.’

Professor Nick White, Professor of Tropical Medicine at MORU, and also the co-lead of the study said: ‘The formalisation of processes in the development of national guidelines for COVID-19 and other infectious diseases is essential for ensuring that these guidelines are grounded in the best available evidence. A systematic and structured approach would not only enhance the credibility of the guidelines but could also contribute to their effectiveness in guiding public health interventions, especially in a pandemic setting.’

Significant variations in national COVID-19 treatment recommendations have been suspected since the advent of the pandemic, but these haven’t been formally quantified or studied in depth, note the researchers.

While COVID-19 infection is no longer taking the toll on lives and health that it once did, the virus is still evolving and active around the globe with significant mortality for the most vulnerable populations without adequate treatment, with the WHO declaring it to no longer public health emergency only in April 2023.

To assess how well national clinical practice followed WHO recommendations (regarded as the gold standard) for COVID-19 treatment, the researchers analysed all 194 WHO member states’ most recent and available national guidelines at the end of 2022.

They scored each set of guidelines according to how closely they aligned with the WHO recommendations, with extra points awarded for those that were updated within the last 6 months, those that made recommendations in line with the strength of evidence, and those that included assessments of the effectiveness of treatments and their side effects.

The wealth and resources of each country were then compared using per capita World Bank gross domestic product (GDP) in US dollars for 2021, the Human Development Index 2021, and the Global Health Security Index (GHSI) 2021.

Of the 194 countries, 72 guidelines could not be retrieved. Of the remaining 122, 9 had no formal guidelines or guidelines couldn’t be accessed, and a further 4 didn’t recommend any treatments. These were therefore excluded, leaving a total of 109 analysable guidelines.

The countries for which guidelines weren’t obtained had, on average, smaller populations, lower GDP per head, and a lower GHSI, indicative of greater economic challenges and less ability to respond to health emergencies.

Inconsistent definition of disease severity: the 11th iteration of the WHO guidelines categorises disease severity, but most of the reviewed guidelines (84%;92) didn’t define COVID-19 severity in the same way, and some didn’t define severity at all (6.5%;7). Only 10 guidelines (9%;10) used disease severity definitions that were comparable with those of the WHO.

No assessment of certainty of therapeutic recommendations: most (77%; 84) national guidelines didn’t include an assessment of the strength or certainty of the therapeutic recommendation.

A wider range of recommended drugs: the range of recommended drugs, irrespective of severity, varied from 1 to 22. The WHO guidelines recommend a total of 10.

Mismatch with WHO guidance: in all, 105 guidelines included at least one treatment recommended by the WHO, but 4 didn’t recommend any.  Countries in the African region had a significantly lower proportion of therapies recommended by the WHO, compared with countries in Europe and South East Asia.

The full story is available on the IDDO website

Read the publication 'Comparison of WHO versus national COVID-19 therapeutic guidelines across the world: not exactly a perfect match' on the BMJ Global Health website