A box of Plaquenil (hydroxychloroquine) is seen at a drugstore in Paris, France, April 29, 2020. (Photo by Aurelien Morissard/Xinhua)

The medical journal has issued an "expression of concern" over a large-scale study of hydroxychloroquine and chloroquine that led to the World Health Organization (WHO) to pause clinical trials of the former as a potential treatment for COVID-19.

The WHO said hydroxychloroquine trials would restart after a safety review found there was no reason to modify the trial.

The Lancet acknowledged "important" questions over the research into the anti-viral drugs, after dozens of scientists issued an open letter raising concerns about its methodology and the underlying data, which was provided by the US-based firm Surgisphere.

"Although an independent audit of the provenance and validity of the data has been commissioned by the authors not affiliated with Surgisphere and is ongoing, with results expected very shortly, we are issuing an Expression of Concern to alert readers to the fact that serious scientific questions have been brought to our attention," The Lancet said on Tuesday. 

While an expression of concern is not as severe as a journal withdrawing a published study, it signifies that the research is potentially problematic.   

The observational study looked at records for 96,000 patients and concluded that treatment with hydroxychloroquine, which is normally used to treat arthritis, and chloroquine, an anti-malarial, showed no benefit in the treatment of COVID-19 and even increased the likelihood of patients dying in hospital.

"We are now fairly confident, not having seen any differences in mortality, that the data safety monitoring committees of both solidarity and recovery have recommended that the trial can continue," the WHO's Soumya Swaminathan told a press briefing on Wednesday.

France was among the countries to also halt COVID-19 treatment with hydroxychloroquine. 

The study whipped up fresh controversy over hydroxychloroquine, which has been endorsed by public figures - including US President Donald Trump - despite concerns over side effects and a lack of evidence that it is effective.  

The study's authors, led by Mandeep Mehra of the Brigham and Women's Hospital in the US, looked at data from hundreds of hospitals between December 2019 and April and compared those who received either of the two drugs - with or without an antibiotic - with a control group.

It followed numerous smaller studies that suggested hydroxychloroquine is ineffective in treating COVID-19. However, in an open letter on May 29, a group of scientists raised "both methodological and data integrity concerns" about it. These included a lack of information about the countries and hospitals.