Dental Tribune India

Lancet faces severe criticism from scientific community: Hydroxychloroquine study is hiding data

By Rajeev Chitguppi, Dental Tribune South Asia
May 30, 2020

More than 100 scientists and clinicians have sent an open letter to The Lancet's editor, Richard Horton, and the paper's authors asking them many uncomfortable questions, but have failed to receive convincing answers from the authors. How can a drug like Hydroxychloroquine produced in such huge quantities for a country as populous as India, safely consumed by millions & millions of chronic users for so many decades without any adverse effects, suddenly get a negative report in 2020 when it's most needed for a pandemic such as COVID -19?

A study of 96,000 hospitalized coronavirus patients
Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis published in The Lancet found that those who received hydroxychloroquine (HCQ) had a significantly higher risk of death compared with those who did not. The study concluded that individuals treated with HCQ (or the closely related drug chloroquine) were also more prone to develop arrhythmia, that can lead to sudden cardiac death.

After the publication of this controversial article, the World Health Organisation's (WHO) advisory suspended the use of hydroxychloroquine (HCQ) in COVID-19 patients. This came as a big shock to India, the second most populated country in the world, where HCQ is produced in large quantities to meet the demand of treating a large number of Malaria patients. The disappointment was huge because The Lancet study showed distinct harm, apart from no real benefit to the COVID- 19 patients. A negative report against HCQ in times when the drug is needed all over the globe urgently appeared unbelievable to the Indian health authorities who have witnessed the long use of HCQ, safely consumed by millions & millions of Indians without any adverse effects for so many decades. 

Indian authorities quickly swung into action. First, it was the Union Health Ministry of India that expressed reservations about the  WHO's advisory to suspend the use of HCQ in COVID-19 patients. Now, it's the Indian Council of Medical Research (ICMR) that has written to the WHO citing the differences they have found in dosage standards between Indian and international trials. This is a significant finding that could explain the HCQ efficacy issues in treating COVID-19 patients.

Currently, the Indian protocols to treat severe coronavirus patients in ICU, recommend a 5- day course. First, a heavy dose of 400mg HCQ (morning & night) on the first day, followed by 200 mg HCQ (morning & night) for the next four days. The total dosage of 2400 mg administered to a patient in 5 days.

Indian officials disagreeing with the WHO's advisory believe that the dosage levels given in the international trials are massive- 800 mg x 2 loading doses 6 hours apart followed by 400 mg x 2 doses per day for 10 days. This makes the total dosage - 9600 mg given over 11 days -about four times higher than the one given in Indian patients.

ICMR officials have found their low dose HCQ protocol to be efficacious enough that has helped the COVID- 19 patients in India to recover quickly.  They are of the opinion that there was no reason for the WHO to suspend the trial for safety concern.

The hydroxychloroquine (HCQ) efficacy issue has generated a lot of debate globally as well. The Lancet study is now under severe criticism from more than 180 scientists worldwide for not releasing the data for an independent analysis outside.

The scientific community is furious seeing a poorly written and poorly executed study published in The Lancet that has not only received huge underserved publicity but also created a massive negative impact on the other judiciously planned clinical trials being conducted around the world. More than 100 scientists and clinicians have sent an open letter to The Lancet's editor, Richard Horton, and the paper's authors asking them many uncomfortable questions, but have failed to receive convincing answers from the authors.

Read the open letter here

The letter alleges that

  1. the authors have not adhered to the standard practices of the scientific community
  2. the authors have not disclosed the data or the code.
  3. the study has not gone through the mandatory ethical review
  4. the authors have not mentioned the locations (countries/ hospitals) that have contributed to the data.
  5. plus many more unscientific, unethical and questionable standards applied.

Meanwhile, Professor Harvey Risch, MD, Epidemiologist from Yale University has recommended an early therapy with Hydroxychloroquine & Azithromycin in the early therapy for COVID-19. His study Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis has been published by Oxford University Press, on behalf of the Johns Hopkins Bloomberg School of Public Health.

Brazil health ministry questions the Lancet study on HCQ, stands by Hydroxychloroquine and continues to support the use of HCQ.

54 Comments

  • Amol Thorat says:

    To good a review. Of late, it has been observed that the credibility of Lancet as well as WHO is on a decline

  • Dr SK Gupta says:

    Richard Horton, Editor Lancet is Plagued by Anti India sentiment and in his frenzy he is playing with lives of millions of people by eroding their confidence in Safe Effective and time tested drug HCQ.

  • Narayan Rao Damera says:

    ICMR the nodal agency for medical research in India has upgraded the use of HCQS as a prophylaxis against Covid19. Now all the frontline workers like police, sanitation workers etc. are also advised to take HCQS as a prophylaxis. Prior to this only healthcare providers were advised to use HCQS as a prophylaxis. The protection offered is phenomenal. Good call from ICMR.

  • DR. M. K. SUDARSHAN says:

    WHO is an ivory tower ,much glorified by some for reasons other than science. WHO has staff and scientists and and like any other humans do err, some times by chance and some times by choice. Let us have self belief and trust Government of India, ICMR and some times even local experts in the states

  • Nita says:

    HCQ needs more research for efficacy and safety profile

  • George Paul says:

    I cannot believe that a drug that has been extensively used as an anti malarial drug in South Asia and Africa with no alarming side effects for decades is suddenly seen as a great danger because it is not a readily available in the West and they have to depend on countries like India. I have no solid reason to believe that it might help significantly but it certainly is not a terrible risk as it is made out to be. The important test is to pit perceived risk vs benefit.

  • Prakash Sanzgiri says:

    An Orphan, cheap drug without Godfathers, and no benefit to Pharma corporates is no competition to a Richie-rich molecule like Remdesivir from Gilead.

    WHO is an inconsequential organization which deserves a COVID burial in an unmarked grave.

    SARS COV 2 virus has taught us a lot. It’s presentation is varied, depending upon VIRUS LOAD , IMMUNE RESPONSE , HYPER-REACTIVITY OF IMMUNE SYSTEM

    Investigations play big role in mangement. Unfortunately most desired tests are unavailable in smaller centers, and often doctors are unaware of those tests. Drugs for cytokine storm are costly and unavailable.

  • Fariduddin Shaikh says:

    Sir with due respect to all the medical practitioners around the world I would like to add doctors in india are really very hard working and updated. When such studies come in circulation it should be verified independently and than a relevant conclusion should be presented. These guys mis guided millions and this is a big blunder. WHO needs new recruitment as it is full of exhausted guys. We follow one principle in our practice if you are not sure keep your mouth shut. Extremely sorry if I offended someone

  • Lancet journal has lost its credibility and is making fool of scientific community. It is playing with millions of lives just for money given by some vested countries and people .

  • Shyamapada Mandal says:

    CQ/HCQ is a drug of choice for malaria since long time, now also giving life protection from COVID-19. AntiIndia feeling by the lancet editor supporting publication of paper with poorly studied data will mislead the ethics of Indian Medical Science standards. More research is needed for effective conclusion and global information.

  • Chloroquine and Hydroxychloroquine are best started on exoposure to COVID19 positive case and continue for atleast 8_12 weeks.
    Also very effective in early stage with in 8_19 days of exposure.
    May not be very effective when started after clinically SARI presentation.

  • M.Narayana Reddy says:

    HydroxyChlroquineSo4 should be reconsidered in management of Covid-19 as propylaxis and as curativr

  • Dr Anil Mehndiratta says:

    I have been using HCQS extensively for years in Various connective tissue disorders without any side effects. How can lancet suddenly say that it’s a very toxic drug.? Even it has side effects, in this kind of pandemic one should see what benefits it has over the minimal side effects and how much it can help to save lives.

  • Ila singh says:

    Sinister role of Lancet and WHO in collaboration with drug companies. I mean it’s a common sense how they affect a market. Lancet and WHO shouldn’t spoil there reputation.

  • Dr Prabhat Gupta says:

    We have never seen trials being halted like this.Trials are truncated midway only when there is overwhelming evidence that continuing trial of a particular drug can be dangerous to the life of participants. Did interim results of HCQ in solidarity trial show any such evidence? Why should WHO take cognizance of a report in Lancet when it’s own trial is continuing..

    Director WHO Dr Tedros seems to be under pressure of US Pharma giants pushing their products.

  • Dr Jayanta Kumar Saha says:

    From the very beginning of covid 19 in India myself and many other doctors and heath personals are taking Hydroxychloroquine as prophylaxis apart from therapeutic trials ongoing in India. And it is being used for so many years in Rheumatoid arthritis for years togethe. No questions about safety is arisen so far.WHO is fearing business loss of their western ‘Lords ‘ .. perhap. And losing It’s credibility as scientific body.
    India should continue ongoing trials of this drug as prophylaxis and therapeutic for covid 19.

  • Dr Kiran Belsare says:

    I never believed this study….have been using this drug since more than 25 years in patients of arthritis and in diabetics since the last couple of years with no significant side effects…..how can the trust built up over years with experience be set aside by just one study….this being a low cost drug was expected to be booed by the west

  • Prof Dr Vivek GUPTA says:

    I completely agree for the moment HydroxyChloroquin is the best bet in both prophylaxis and treatment

  • Dr surendra shantilal shah says:

    Pl can i get information .
    As of completing prophylactic dosage of 7 weeks.
    What Will be next schedule as an prophylactic

  • Ramesh Dargad says:

    We are using hydroxychloroquin regularly for type 2 diabetes as new approved indication in india for thousands of patients many elderly without any cardiac side effects

  • Suresh Vasistha says:

    Lancet and WHO (CHO -China Health Organization) are sold out. The Journal is behaving like paid media. It transgressed it’s domain earlier by commenting on Article 370 in Kashmir and again on Lockdown and migrant labour showing typical colonial attitude and bias towards India.

  • chris camus says:

    the lancet study is using a database that never existed : you can hardly have 20 hospital contributing to such a program , how could they have 600 hospitals from different countries = this lancet article is pure fiction ,
    the only explaination would be that the remdesivir money arranged the whole story, possibly with some melinda and william gaites dollars to convince Mr Lancet

  • ASHOK KUMAR PANDEY says:

    Let us be rational not emotional. I have many of my patients taking HCQ continuously for months in connective tissue disorders, except for a very few who needed disconuation for the well known adverse effect of retinopathy hence we advise annual opthalamoscopy
    Let’s give Lancet the benefit of doubt. As we know COVID 19 is not a homogeneous disorder.It appears to be affecting every system of the body acute cardiac injury one of them hence it may be that in COVID 19 cases the drugs may be behaving in a different way; may be toxic to more than usual number of patients seen hitherto.
    Seeing the magnamity of COVID 19 Let LANCET publish the details of it findings .
    But anyway it’s quite unlikely that HCQ which has millions of patients years history would be harmful if given at the beginning of Symptoms.

  • Dr. Lalit kumar says:

    It’s very painful to see such a callous attitude by Lancet. This is seriously going to erode its reputation and credibility. India is doing exceptionally good at this time of COVID-19, however just opposite is reflected in few articles published by Lancet.

  • M.V. Kumar says:

    Richard Horton has behaved like a novice editor with clear biases paid or otherwise in this instance. How can such an article with clear research flaws be accepted for publication. Shame on you for bringing disrepute to research articles.

  • Dr Manish Badkur says:

    Excellent explanation ,I think west studies are influenced by sponcers to sale there costly medicines.they cant except cheap treatment, as in west cost is no bar due insurance coverage.

  • Satish Mocherla says:

    I am surprised that all want to bash Lancet but no one wants to say any thing about the ICMR study which is not randomized, non placebo controlled for prophylaxis …

  • Major General Harinder Singh says:

    Major General Harinder Singh
    l have used chloroquine extensively forchemoprophylaxis against malaria amongst all our troops posted in endemic North Eastern region. There was not a single case of severe side affect warrenting discontinuation of treatment protocol.

  • Dr B P Chattopadhyay says:

    Any recommendation from WHO and any publication in Lancet is respected worldwide.However both the esteemed institutions have been plagued by heads negligent of responsibility of ensuring the ethical and moral standards of research based recommendations/publications paving the ways of speculating unethical compromises on their behalf.

  • Dr Jose chacko Cherackal says:

    The Lancet report is hurriedly compiled one. A 35% increase in mortality due to HCQS should have reflected in other studies of the same drug being used in rheumatology for much higher cumulative dose. There seems to be a hurry in discrediting HCQS . The cardiac toxicity is rather exaggerated.

  • Sunita Prakash says:

    I suggest a counter article in lancet by ICMR with relevant data & eleminating the flaws of lancet study at the earliest to enable us to continue use of HCQ without bias

  • Srinivas says:

    I wrote a few days ago in YouTube videos regarding how the HCQ trials “were made to fail”.
    More than any negativism towards HCQ arising from anti India (since it produces the largest quantity of HCQ in the world) prejudice, the overwhelming prejudice (In my opinion) has arisen from anti Trump sentiments within the media and other quarters. The day Trump said HCQ was a “Game Changer” He drew ridicule and contempt.
    To prove that Trump shot his mouth off they decided HCQ must fail. That’s what the trials show.
    Had Trump said that Remdesivir was a “Game Changer” I wonder if they would have done the same thing. In fact Remdesivir was made to succeed despite its minimal benefit on mortality and enormous cost and difficult scalability. These kind of politics and dirty games unfortunately derail the treatment course and take lives. I congratulate the ICMR for having the gall to take on WHO and the authors of the lancet study by pointing out their mistakes.

  • Rajesh says:

    Anything that cannot be patented is not kosher. Lots of studies are advocating statins, anti dia drugs, weight loss, calorie restrictions…. However, very few are making waves. The news is clogged with new vaccines. News about trials with BCG are nowhere to be seen. Again, the common denominator is off patent, cheap BCG does not stand a chance. Science and health are hostage to patent laws and greed.

    Finally, we need new patent laws for off label uses of old medicines. A treasure trove waiting to be exploited.

  • Dr Nitesh bauddh says:

    Ok..
    I agree that the side effects were over emphasised and may not be true….
    But till now we do not have any good evidence to show that this drug is iseful in prophylaxis. Also there have been few negative trials showing no benifit of hcqs on covid outcomes…
    So may be its not harming as much as what lancet told…but weather its helping needs to be proven yet.

  • Subramanyam Bhupindra says:

    I wouldn’t worry too much. We know HCQ helps reduction in viral load and possible prevents mild turning into severe covid. Cambridge and Brighton school have started HCQ trial for prophylaxis use. We should start our own trial and share data. Of course there’s lot of conflict of interest as HCQ is generic and costs pennies compared to novel antivirals.

  • K.G.Bhat says:

    I have no opinion with WHO or the journal.
    We in India have been using HCQS for rheumatoid arthritis day in and day out.It is been tried even for the chikun gunea arthritis.
    I have found it to cause gastritis in some and no cardiac problems.

  • Dr G Sampath says:

    ICMR has rightly supported the use of HCQ in the prophylaxis and treatment of Covid 19
    Chloroquine and HCQ have been successfully used in India for other conditions for the past many years
    The editorial board of Lancet seems to be biased against India

  • SRRAMASWAMI MD OCALA FL says:

    The following inference one might say can be obtained from review of literature originating from Australia, Brazil, China, England, France, India, S.Korea, Spain, Thailand USA and elsewhere.
    We are all aware of paramount confusion obtained from review of this literature from different parts of the world.
    I might say the following might clear up some of the confusion. We need to classify COVID 19 into three categories based on epidemiological review of the disease.It seems the the more the clustering of people the more the incidence, prevalence, morbidity and mortality of this virus. Various factors can be attributed to this condition, such as underlying natural resistance due to the populations prior exposure to multiple previous illnesses, environmental climate, social distancing, self isolation and so forth. All these conditions might lead to viral load, I am proposing!
    Following the above criteria the classification are as follows:
    1. Prior to exposure to the virus.
    2. Early exposure to the virus with low viral load.
    3. Late exposure with high virus load.
    1. I consider that the prophylaxis prior to exposure to virus might the most useful, similar to a person entering a malaria endemic area. Literature suggests that Hydroxychloroquine can be be used for 5.5 yrs without complications and chloroquine can be used for app. 3 yrs without problems. that is once a wk dosing for example HCQ 400 mg Qwk with Zinc 30 mg QD. May be Ivermecitin can be added once every 6 months dosing. You might mostly use HCQ due to lower dose usage, more effectiveness and less side effects.
    2. The current protocol of higher doses of HCQ 400 mg BID x day followed by 400 QD x 6 days probably is beneficial in early days of phase with lower viral load resulting good results in moderate no of cases.
    3. In case of later administration of above protocol might not yield good results.

    All of this probably mostly related to viral load thus resulting in different results in different groups and causing confusion.

  • Vishnu Kalidindi says:

    The editor of Lancet should come out and explain more. The reputation of Lancet is slowly deteriorating. Earlier also they published anti India articles without any substantiation

  • Dr Renu Dixit says:

    How can lancet publish such article without really working on it. We in india hv been using HCQ from years. I myself has taken chloroquine for 14 days regularly morning n evening injectable when my condition was very bad n Without any side effect except nausea. I survived today to write this just bcoz of this drug. Pl check ur data don’t be puppet in the hands of Pharma mafia. Just give the right picture. In india most of the doctors who are frontliners in covid are taking it as prophylactic. Rethink. Save the lives of people with simple drug.

  • kailash singhal says:

    We are using Hcqs in different indications since yrs together without any major side effect.lacet report article seems to be biased as India is the mazer menufrcturer of the drug

  • Prof Alade Akintonwa says:

    Chloroquine is a popular antimalarial agent with a known side effect as pruritus which can be relieveved by giving antihistamine. In Nigeria,we have usrd thr driug for malaria for over 40yrs. I have pulished several report on it and nrver exprrienced any cstdoac repory. Thr lancey repott fail yo detetmine the plasma leveld at each dosage level most expecially at 800mg. The only reason for discontinustion pf oys use is die development of resistance by plasmodium It is unfortunate that the who interupted its own stidy based on yhr inverified report from 600 hospitalkind of doubtful
    . However Nigeria is continuing with its trial.
    Alade Akintonwa.Toxicology Rrsearch Lab.Lagos Nigeria.

  • Antonio Rohrbacher says:

    I always thought that The Lancet was a serious publication.
    After reading this study, I got the impression It is just a medical The Guardian…

  • STEPHANE says:

    Seems the Lancet is no longer working for the promotion of best medicine but for hidden agendas.
    Sad. For science and mostly for patients.
    At this stage the science is very compelling that HCQ, azythromycin and zinc taken together at the onset of symptoms have a wonderful effect on the course of the disease, its complications, intubation, and mortality.

  • Anju Sinha says:

    WHO should continue the trial with the HCQ arm. Data from a prospectively conducted trial would be scientifically more valid as compared to the retrospective analysis from a registry claiming large sample size.
    We need more evidence to disprove the claims of Lancet publication

  • Dr. Vijayaraghavan says:

    It is really a surprise that such a reputed and highly resected medical journal made such an error of judgement. It would have been perhaps justified to publish the article, with comments by the Editor, cautioning about the conclusions as much higher dose of hydroxychloroquine was used in the study. What is even more startling is the haste with which the WHO stepped in. Was Trump’s assessment of the WHO justified, in view of this action of the WHO?

  • Sharad G says:

    It’s all about Pharma lobby.
    And hydroxy chloroquine was never used as antimalarial as per government of India’s guidelines.
    Most shocking was use of bedaqualine by India under supreme court’s order, not approved by FDC in World is used 1st line medicine in drug resistance tuberculosis.

  • Dr Gajanan Gaude says:

    It’s all Pharma lobby of the rival company . Let there be a randomised trial comparing large no pf pts. Then we can have good comparison data of whether it works or not in covid19.

  • Dr Kunal Chatterjee says:

    We in the Indian Armed Forces have vast experience in the past of using Chloroquine and hydroxy chloroquine. Our soldiers have been placed in areas where malaria is endemic. And these drugs have been extensively used for prophylaxis and treatment. Prophylaxis was peculiar to military use and treatment was as per National guidelines. No major drug related reactions have been reported and it was the drug if choice. Hence the report of Lancet and response of WHO in stopping trials are baseless and over-the-top, without scientific basis.

  • Dr A K Bera says:

    To ban HCQ is a biased study,adverse effect for which it was banned is not found over several decades of its use in personal practice. Lancet has lost its credential by publication of such a baseless paper.

  • Dr A K Bera says:

    To ban HCQ is a biased study,adverse effect for which it was banned is not found over several decades of its use in personal practice. Lancet has lost its credential by publication of such a baseless paper. With this new information, we’re really thankful.

  • I don’t believe that HCQ is as toxic as it is portrayed in the LANCET study, by all means it is FAKE .
    I have nearly 2 decades of experience with this drug and have used it extensively in my patients of arthritis and lately, diabetes without any significant side-effects apart from mild gastric ones.
    So, I am sure that there is some vested interest in discouraging this cheap and time-tested drug.
    Of late, both LANCET and WHO seems to have lost their credibility and are in hands of money minded entities.

  • Tarun Sahni says:

    The pandemic has revealed the underbelly of how medical practice is influenced by selfish individuals and/ or organisations .

    The current evidence is towards a role of HCQS and Chloroquine in COVID and we hope the Lancet and WHO will acknowledge their error

    Meantime we will continue to recommend it to our COVID patients and for prophylaxis

  • M .S . Rawat says:

    Doses are extremely high in the study published in Lancet.We use half the doses. Hence side effects are many. Further controlled trials are mandatory independently in multiple centres .Don’t discard a drug proved useful in the past for many indications. D

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