“…Major Stuart McCarthy said the committee’s report was based on “poor and misleading advice” from senior veterans’ affairs and defence staff to the minister for veterans’ affairs, Dan Tehan. He said evidence had emerged since the trials that known serious side-effects of mefloquine were more prevalent than soldiers were told.
McCarthy joined the army in 1998 and was part of another controversial anti-malarial drug trial, for the unregistered drug tafenoquine, after being deployed to Bougainville in 1999. In 2001, during six months deployed to Ethiopia and Eritrea, he was prescribed mefloquine and experienced adverse side-effects including depression.
He continued to suffer neurological symptoms that he believes are due to a neurotoxic brain injury caused by the drug. In January 2016 McCarthy was diagnosed with an acquired brain injury. He was medically discharged from the army in March.
He said the steering committee report downplayed the seriousness of the side-effects by emphasising the small numbers of ADF personnel prescribed mefloquine between 2010 to 2015. But the drug had used by several thousand personnel since its introduction in early 1990s, he said.
“The main issue of concern is the chronic health effects experienced by the 5,000 personnel given mefloquine and tafenoquine since the early 1990s,” McCarthy said. “Drug regulators including the US Food and Drug Administration warn that mefloquine is able to cause neuropsychiatric side effects that may persist or become permanent.
“Extensive research dating as far back as the 1940s found that several drugs from this class are able to cause lasting or permanent brain damage. Many ADF veterans who were given mefloquine or tafenoquine have since suffered serious health problems including bipolar disorder, schizophrenia, major depression and anxiety, seizures, hallucinations and psychosis, suicide attempts and suicide…”
A PROPOSAL for a pilot outreach program to help veterans affected by antimalarial drugs has been rejected, with the Department of Veterans’ Affairs saying existing support services are adequate.
The decision has angered veterans who participated in controversial ADF sanctioned mefloquine and tafenoquine trials, and their families, some of whom are caring for those with mental health issues.
They now want to meet with Prime Minister Malcolm Turnbull, who has previously committed to tackling veteran suicides, an issue linked to the use of the drugs.
Lavina Salter, whose husband Chris has suffered adverse mental health after taking mefloquine during a deployment to East Timor, said the proposal rejection had left her feeling defeated.
“By their own admission, DVA has said they don’t know the full extent of the number of veterans affected by these drugs so why don’t they do something?” she said.
“We will keep trying because we can’t give up on these guys.”
The Quinoline Veterans and Families Association submitted a proposal to Veterans’ Affairs Minister Dan Tehan in December for a first-of-its-kind Veterans Outreach Program. The initial budget was $2.25 million per annum for an initial period of five years.
The program would include new research, the identification of all personnel administered mefloquine or tafenoquine during their ADF service and assist affected individuals.
QVFA co-convenor Major Stuart McCarthy, who was prescribed both mefloquine and tafenoquine by the ADF, said rejecting the program was “indefensible” because existing services were clearly not adequate.
“I can accept that Dan Tehan wouldn’t necessarily have signed up to the proposal straight away, but to come back with a blunt no and to not enter into further discussion or dialogue is unacceptable,” he said.
“We have made repeated efforts to engage with DVA and work with them to develop health outreach both for veterans and their families and that’s why we did the proposal because those needs are not being met.
“It’s really time now for the Prime Minister to provide leadership on this, because the departments of Defence and Veterans’ Affairs have completely failed.”
In a short statement, Mr Tehan told the Bulletin yesterday he believed the Federal Government was already responding to concerns about the use of mefloquine by the ADF.
“The existing services and additional support the Government has implemented are meeting the needs of the ex-service community concerned,” he said.
“….India, where a lot of clinical trials have already begun, is likely to get a breakthrough anti-malarial drug Tafenoquine by 2018. The drug, a one-day two-dose treatment, has already entered phase-three trials and once approved will replace the current 14-day treatment for plasmodium vivax malaria, which is prevalent in India…’
“…Many of them have since suffered an illness classified as an Acquired Brain Injury. There is sturdy scientific proof that ABI can occur after treatment with mefloquine. Scientists from the US military research institute that developed the drugs found that mefloquine was able to cause a “lasting or permanent” brain injury. Other scientists at the same institute found tafenoquine, an experimental drug that has not been registered for sale anywhere in the world, “is more neurotoxic than mefloquine”….
The anti-malarial drug trial scandal that has embroiled the Australian Defence Force for the last two years simply won’t go away, despite the government’s best efforts to whitewash the controversy with a flawed “military justice” inquiry.
There are growing calls for a public inquiry to investigate ethical breaches which occurred during a series of Army Malaria Institute (AMI) clinical trials conducted in Bougainville and Timor Leste from 1999 to 2002.
The drugs in question are mefloquine, a neurotoxicant able to cause a “lasting or permanent” brain injury in a sizeable minority of users, and the experimental drug tafenoquine. The latter was found to be “more neurotoxic than mefloquine” by scientists from the US military research institute which developed both drugs.
Tafenoquine was given to more than 1,500 ADF personnel during these trials, while mefloquine was used on 1,300 personnel. Mefloquine has probably been given to an additional 2,000 personnel since its introduction in the early 1990s.
Hundreds of Australian veterans have since been diagnosed with serious neurological and psychiatric disorders, often mistaken for post-traumatic stress disorder. Many maintain they were compelled to participate in the trials. The Department of Veterans Affairs (DVA) has belatedly launched a health outreach program, admitting that the first cases “could be the tip of the iceberg”.
Media attention has to date focused on the health concerns of those affected and the ethical question of whether the subjects provided fully informed consent.
Yet a deeper question is emerging, namely a fundamental conflict between the commercial interests of the pharmaceutical industry and the public interests of the ADF. This could even result in criminal charges against ADF medical officials who conducted the trials and now hold senior military appointments.
How could the ADF leadership have allowed this to happen?
Mefloquine and tafenoquine are both products of the US Walter Reed Army Institute of Research (WRAIR) anti-malarial drug discovery program which commenced during the Vietnam War. The results of early military tests of mefloquine were given to the manufacturer Roche in one of the first public-private partnerships of its kind. These questionable results were then used to shortcut the approvals process by the US Food and Drug Administration (FDA) and other regulators.
By the late 1990s mefloquine was well known for its serious side effects and fell out of favour to the extent it is no longer manufactured by Roche in many countries. Linked to numerous war crimes, murders and suicides over the last 15 years, mefloquine is now banned or regarded as a drug of last resort.
Tafenoquine is already repeating this tragic history, with the direct involvement of WRAIR and the closely affiliated AMI.
The ADF’s deployments to Bougainville and Timor Leste provided an ideal opportunity for AMI and WRAIR to conduct large-scale drug trials on a captive pool of “volunteers”. Tafenoquine and mefloquine were tested on almost every battalion of the Royal Australian Regiment. The results of several of these trials have not been published, presumably because they were unfavourable.
Of the reports that were published, none commented on the serious adverse effects that emerged from the trials. One report that was published found there was “no statistical difference” between tafenoquine and mefloquine in the rate of neurological and psychiatric side effects. Many of the subjects are to this day admitted to psychiatric hospitals or have subsequently suicided — yet the ADF has refused to conduct follow up health studies.
A co-author of the published study has been stonewalling the proposed outreach program for years. Recently, he falsely informed doctorsinvolved in the outreach program that there were “no recorded neuropsychiatric side effects” from tafenoquine; contrary to his original report which found one in eight of his subjects experienced such side effects.
The results of this trial were re-analysed in a 2014 paper co-authored by the current Director of AMI to find that tafenoquine is 100% effective in preventing malaria. The lead author of this paper is a former WRAIR employee who now owns a niche pharmaceutical company awarded a contract by the US Army to develop the drug for registration with both the FDA and the Australian Therapeutic Goods Administration. Should the FDA approve, his company would be given a tradeable “priority review voucher” worth several hundred million dollars.
In the 1990s the Canadian government responded to a similar scandal involving an unlawful mefloquine drug trial on peacekeeping troops in Somalia by disbanding the regiment that was subjected to the experiment.
On the evidence already publicly available, a more appropriate response from the Australian government would be to disband AMI and prohibit the conduct of clinical drug trials on ADF personnel deployed on military operations. The ADF is clearly incapable of providing the corporate oversight needed to protect the interests of its troops against those of the pharmaceutical industry.
Townsville veterans angry over lack of consultation for adverse effects of antimalarial drug trials
December 6, 2016 12:00am
VETERANS who believe they have been adversely affected by Defence-sanctioned antimalarial drug trials are angry they were not consulted about the delivery of an urgent “outreach program”.
Official letters about the program only began circulating yesterday after the Bulletin revealed last week an outreach program was to be held in Townsville next week for former ADF members and others concerned about mefloquine or tafenoquine.
The Department of Veterans’ Affairs told the Bulletin it also planned to begin an advertising campaign for the program from today.
Melbourne-based veteran Michael Kruizinga said he was given tafenoquine after contracting malaria on the drug Doxycycline before being given mefloquine on a second tour of East Timor.
He recently helped organise a health forum in Melbourne and said people there were desperate for help and would have liked to be consulted on a possible program.
“It’s absolutely pathetic the way the Government has played this because this program is absolutely necessary,” he said. “Groups have been pushing for this outreach program and it seems they’ve just rushed it through to get us off their backs.”
DVA said the concept for the outreach was developed by the DVA-Defence Links steering committee.
“All material that is provided to attendees of the outreach program will be available online, supplementing current information on both DVA and Defence websites,” a DVA spokesman said.
“This will include the names of Townsville-based GPs who are currently known to DVA as being able to assist individuals who may present with symptoms or conditions that they attribute to having taken mefloquine while in the ADF.”
Six sessions are being offered and can accommodate about 50 attendees at the Townsville VAN Office.
“The Townsville outreach sessions will be evaluated and this will help inform the Government as to what additional steps should be taken to assist veterans with concerns,” the spokesman said.
Retried colonel Ray Martin said the Government made an election commitment to set up an open dialogue, but he believed this had not occurred.
“To announce a program with little notice, when many are unavailable, away or on leave, without consultation, input or feedback — from those most affected is very disappointing,” he said.
WHEN you sign up to fight for your country, you accept you have to put your life on the line. In recent years, scores of those who have served in dangerous or inhospitable places haven’t made it home. To them we are grateful.
Those such as the 41 who were killed in 14 years of the Afghanistan War, faced traditional opponents. That enemy carried weapons. They laid roadside bombs. And the horrors of what many experience last well beyond deployment and into an unsettled civilian life. Many, as revealed by government figures last week, have taken their own lives.
But PTSD isn’t the only hazard that can cause impairment in our Australian veterans. Since the late 1980s, 5000 personnel were administered two antimalarial drugs — mefloquine and the experimental tafenoquine — when sent on military service in countries with a malaria risk.
Many of them have since suffered an illness classified as an Acquired Brain Injury. There is sturdy scientific proof that ABI can occur after treatment with mefloquine. Scientists from the US military research institute that developed the drugs found that mefloquine was able to cause a “lasting or permanent” brain injury. Other scientists at the same institute found tafenoquine, an experimental drug that has not been registered for sale anywhere in the world, “is more neurotoxic than mefloquine”.
Prime Minister Malcolm Turnbull said in August, on the evidence of an alarming veteran suicide rate, that “we have to go beyond the memorials and the monuments and focus on the men and women, the real challenges they face, ensuring that they are supported”. This week, Veterans’ Affairs Minister Dan Tehan and Health Minister Sussan Ley are expected to launch the government’s veteran suicide prevention initiative. With more than 60 veterans having taken their own lives this year, this response is welcome.
Turnbull’s words are encouraging, but there is a glaring omission from his government’s response thus far — an outreach and treatment program for veterans affected by exposure to mefloquine and tafenoquine. Although Defence has recognised that mefloquine can have long-term health effects, Defence and Veterans’ Affairs have initiated no consultation to ensure the advice they are providing to those affected is suitable. Yet Australian veterans who suffer serious, chronic illness since their exposure to the drugs are in the hundreds.
Difficulties in correctly diagnosing this type of brain injury have meant that few of those affected have been able to access the appropriate rehabilitation, medical and other support services. Most who have sought medical help have been diagnosed and medicated for PTSD or other mental illnesses without having been referred to brain injury specialists. That misdiagnosis has led to further disabling drug reactions, family breakdowns, homelessness and suicide.
During this year’s election, the government committed to formal consultation with affected veterans and their families to address these concerns. Despite news of an “outreach” event in Townsville this month, the consultation has not happened. Discussions with senior Veterans’ Affairs medical officers indicated that “consultation was not required”. Meanwhile, Defence and Veterans’ Affairs officials have trivialised the nature and extent of the problems, unfairly suggesting those affected are exaggerating or inventing their symptoms.
The numerous diagnoses of bipolar disorder, schizophrenia, major depression and anxiety, seizures, hallucinations and psychosis, suicide attempts and suicide indicate this is a serious issue. Equally serious steps need to be taken by the government to embrace those suffering and give them suitable assistance.
Providing the right assistance is not hard. There are existing ABI outreach and rehabilitation programs available in every state that receive significant federal funding. Indeed, some fortunate veterans who have persisted to obtain the right treatment are already receiving those services. Sadly, these are in single figures.
If Turnbull is serious about addressing veteran suicides — and there is no reason to believe he isn’t — he should now direct both ministers to make those programs available to all veterans who were exposed to these neurotoxic drugs during their service to the country.
Stuart McCarthy is an army officer who served in Afghanistan, Iraq, Ethiopia and Eritrea and Bougainville. He is undergoing rehabilitation for an acquired brain injury after being exposed to mefloquine and tafenoquine
Documents obtained by Fairfax Media reveal the Therapeutic Goods Administration wrote to senior doctors at the Balmoral Naval Hospital in Sydney to warn they had no authority to acquire or use the drug under existing arrangements.
Six months later, the hospital received 13 capsules of tafenoquine from pharmaceutical giant GlaxoSmithKline to use on a 26-year-old on the condition it would not be held responsible for side-effects.
The company urged the doctors to contact US Army Medical Research and Materiel Command within 24 hours of serious or unexpected reactions by soldiers. It also told doctors to supply detailed records of patient history and health outcomes.
Tafenoquine remains banned in Australia and has been linked to blood cell damage and anaemia. Common side effects include nausea, vomiting, diarrhoea, headaches and eye disease. It was trialled on 461 ADF personnel as part of a clinical trial in East Timor during 2000-01.
A Department of Defence spokesman said the TGA warning related to the treatment of soldiers with recurrent malaria rather than the clinical trials. But correspondence reveals Australia’s drug regulator did not shy from expressing concern about the drug.
Military doctors were initially granted full access to tafenoquine although this was overruled once the TGA realised the doctors would not comply with relevant safety regulations.
The letter, sent by the TGA’s director of drug safety Dr Leonie Hunt, told doctors they were not authorised to use the drug outside a controlled clinical environment and without the approval of a hospital ethics committee.
“It has been brought to my attention that you do not satisfy these requirements and therefore the authorisation should not have been issued,” Dr Hunt said.
“Accordingly you are no longer authorised to supply or prescribe tafenoquine for use in defence personnel for the treatment of recurrent vivax malaria.”
According to the Department of Defence, the warning was the result of “an administrative error” caused when military doctors applied for the drug under the wrong subsection of the relevant act.
The doctors were eventually granted the drug for “compassionate use” under a special access scheme that judged patient needs on a case-by-case basis. Another 30 ADF personnel were treated under the scheme after a spike in malaria cases during 2001-02.
A TGA spokeswoman said the only way to acquire the dug remained the special access scheme.
“Were the TGA to become aware that unregistered products were being supplied without obtaining appropriate exemption, the matter would be investigated,” she said.
GlaxoSmithKline told the military doctors all patients needed to be provided with information about the drug including alternative options. Written consent forms were also required.
“An integral component and condition of approval for supply of an experimental drug is the documentation of safety and efficacy data,” the letter said.
“It is extremely important that we, as the manufacturers of tafenoquine, obtain detailed information regarding treatment and we ask for your co-operation to document details of patient history and therapeutic outcome.”
Patient outcomes were recorded by military doctors at the Australian Army Malaria Institute and published in the American Journal of Tropical Medicine and Hygiene in 2007.
According to the journal article, the authors were full-time ADF employees and received funding from GlaxoSmithKline to present their findings. They insist no other potential conflicts of interest existed.
Andrew George, a former infantry soldier and public relations officer with the Army Reserve, was treated with tafenoquine in Sydney and claims it left him with damaging side effects.
Mr George, who features in promotional material for the reserves, said he was given the drug after being diagnosed with malaria but does not recall giving informed consent after a detailed explanation of the drug.
He is one of many veterans seeking answers about the drugs with many believing it complicated their diagnosis and management of post-traumatic stress-disorder.
“I am still proud of my service,” he said. “I am proud to have done what my dad did – a Vietnam veteran,” Mr George said.
Australian Defence Medical Ethics Committee documents, released late last year under freedom of information laws, showed the ADF was concerned about whether the trials were properly explained to soldiers.
“It would be preferable to have all information conveyed openly and honestly to every member involved in current and previous tafenoquine trials,” the document said. “This will markedly reduce the risk of a perceived cover-up”
Since the release of the document, the Department of Defence has made a catalogue of information about the trials and the drug available for veterans online.
Surgeon General of the ADF, Air Vice-Marshal Tracy Smart, has also met with veterans at a community event in Townsville and insisted the military was being transparent as possible.
Last month, a senate committee called on the Australian Defence Force to explain all potentially damaging side effects of the antimalarial drugs to every veteran or soldier who has taken them since 2001.
Defence force admits soldier shouldn’t have been included in East Timor anti-malaria drug trial
The Australian Defence Force has acknowledged it accidentally exposed one of its soldiers to controversial anti-malarial drugs during trials in East Timor, despite the soldier having a medical history of mental illness which should have precluded his involvement.
ADF apologises for including soldier Chris Salter in anti-malarial drug trial in East Timor
Mr Salter should have been precluded from trial due to history of mental illness
First time ADF has publicly accepted it made mistakes during Timor drug trials
The soldier, Chris Salter, developed chronic depression and psychosis after inclusion in the Timor trials of psychoactive drugs mefloquine and tafenoquine.
His illness has led to repeated suicide attempts and more than a dozen stays in psychiatric hospitals. He is unable to work or care for his family.
Since the trials, which included thousands of Australian soldiers between 2001 and 2003, a small group of veterans have developed severe mental illnesses.
They believe the ADF erred by giving them the drugs even though there was a significant body of research which pointed to the drugs’ side effects, which in some cases are permanent.
The letter to Mr Salter is the first public case of the ADF accepting it made mistakes during the Timor drug trials. It may open the way for other veterans to seek similar apologies and could lead to compensation.
“Following the disclosure by your wife on the 7.30 Report (sic) in June that you were prescribed mefloquine despite a history of depression, I determined that I should conduct a review of your medical documents,” the ADF’s Surgeon-General, Tracy Smart, wrote in a letter late last month.
In that same letter Air Vice Marshal Smart wrote: “I apologise on behalf of Defence that you were prescribed mefloquine given your history of depression. This represented an unacceptable risk.”
Ms Salter has become a vocal critic of Defence, and says the ADF has failed to provide assistance to people who are suffering chronic illness as a result of taking the drugs.
After her husband received his letter she asked people in a mefloquine and tafenoquine support group on Facebook whether anyone had a similar experience.
“I’ve had three or four responses of people who’ve come back and said yes, they were diagnosed with depression and didn’t have a medical to see whether they were eligible [for inclusion in the drug trials],” Ms Salter told 7.30.
All those veterans could be eligible for formal apologies and compensation.
The high stakes of Ms Salter’s campaign for recognition were highlighted two weeks ago, when one of the Timor veterans, Chris Stiles, took his life.
Since then a group of mefloquine and tafenoquine-affected veterans in Townsville have told 7.30 of their anger over the death of Mr Stiles, who was given the drugs and experienced a significant downturn in his mental health.
“It’s happening to a lot of people, it’s not just Chris. Chris is just the latest one, and it will continue happening,” said one of Mr Stiles’s Timor colleagues, Colin Brock.
The veterans say Defence and the Department of Veterans Affairs have failed to provide meaningful assistance and have left many who served in East Timor to shoulder the burden of mental and physical illness caused or exacerbated by the drugs on their own.
Defence has been approached for a response.
Banned or limited by other militaries around the world
Mr Brock helped carry Mr Stiles’s coffin to his grave a week ago. He was one of two of the pallbearers who were given the drugs in Timor and have since developed mental illnesses that have seen them admitted to psychiatric hospital suffering a host of mental and physical symptoms.
Mefloquine — also known as Lariam — and tafenoquine are psychoactive anti-malarials that, according to the World Health Organisation and neurological researchers, have a history of links to severe depression, anxiety, irrational anger, memory loss, suicidal thoughts, psychosis and hallucinations.
Across the world militaries are seeking to ban or limit the use of the drugs, given serious concerns about their side effects.
In 2013 US special operations forces banned the drugs after the Food and Drug Administration issued its highest alert — a so-called “black box” warning.
“Neurologic side effects can occur at any time during drug use, and can last for months to years after the drug is stopped or can be permanent,” the FDA said.
Last year a UK parliamentary inquiry found the Ministry of Defence prescribed the drug too liberally and recommended it be redesignated as a “drug of last resort”.
The ADF’s Inspector-General has launched an inquiry into the East Timor drug trials. He is due to report by the end of this year.
Defence has so far refused to commit to reporting publicly.
Tafenoquine is an experimental anti-malaria drug manufactured by GSK. It seems it might be just as dodgy as Roche’s Lariam (see here). Personally, after experiencing the horrors of Seroxat, I wouldn’t ingest any GSK product, and why would I?
Seroxat was horrific.
A great website worth checking out in relation to these drugs is
“Effectively, all users of Lariam, from the point of licensing onwards, have been involved in a natural experiment to determine the true safety margin, at current dosages, of [this] poorly understood antimalaria drug. Consumers have been unwitting recruits to this longitudinal study, rather than informed partners.”
Much of the recent media coverage of mefloquine’s adverse health effects has focused on the efforts of military veterans, including drug trial subjects, in seeking appropriate recognition and medical care from their national governments. Prominent among these are Australian veterans who participated in clinical trials conducted by the Australian Army Malaria Institute (AMI) in Timor Leste from 2000 to 2002. With doxycycline malaria prophylaxis having been pioneered by AMI in the 1980s in response to resistance in other drug classes, mefloquine has never been the first line anti-malarial in the Australian Defence Force (ADF) and was prohibited from being used by aircrew and other specialist personnel due to its neuropsychiatric side effects. This has led us to question why the drug was “trialled” for use in the ADF long after it had been registered, with its neuropsychiatric side effect profile so evident in the civilian market and previously published military drug trials. What has become apparent is that ADF personnel given mefloquine during these trials were simply “collateral damage” in an effort to support the development of another synthetic quinoline anti-malarial drug – tafenoquine.
The story of tafenoquine’s development and introduction to date is alarmingly similar to the story of mefloquine – marred by regulatory shortcuts, cosy relationships between military officials and the pharmaceutical industry, breaches of ethical standards, scientific fraud and medical negligence. This is the first in a series of posts that aims to document this misconduct by ADF officials involved in the AMI’s clinical trials of tafenoquine. In this post we will provide background on tafenoquine and an overview of the trials, then in subsequent posts we will describe the conduct of each trial and the emerging evidence of misconduct.
Despite these AMI trials having found tafenoquine to be safe and effective, the drug’s clinical development did not substantially progress towards registration for almost decade. Eventually, in 2008 the manufacturer GlaxoSmithKline (GSK) entered an agreement with Medicines for Malaria Venture (MMV) to develop tafenoquine as a radical cure for vivax malaria. Five years later the U.S. Food and Dug Administration (FDA) granted “breakthrough therapy” designation for tafenoquine, and several months later GSK and MMV announced the commencement of Phase III clinical trials. The FDA states that Breakthrough Therapy designation “is intended to expedite the development and review of drugs for serious or life-threatening conditions”, and “conveys all of the fast track program features, more intensive FDA guidance on an efficient drug development program, an organizational commitment involving senior managers, and eligibility for rolling review and priority review.”
Another parallel with the mefloquine story is that there has been a reluctance to undertake laboratory studies of tafenoquine’s potential neurotoxicity prior to registration. Like another 8-aminoquinoline primaquine, tafenoquine is able to cause haemolytic anemia in individuals with G6PD deficiency, and many of the clinical studies have carefully assessed this toxic property. However the 8-aminoquinoline class includes several other drugs that are also known to be neurotoxic, including pamaquine and plasmocid, based on extensive histopathological testing conducted as long ago as the 1940s. A leading expert in quinoline toxicity wrote in 2013:
“While tafenoquine has been eagerly anticipated for its utility against vivax malaria and potentially against leishmaniasis, the recent granting by the U.S. FDA of Breakthrough Therapy status, in the absence of any published neurohistopathological testing, risks recreating the sense of urgency that contributed to the approval of mefloquine in the absence of appropriate CNS safety data.”
Several years after the AMI’s tafenoquine and mefloquine clinical trials in Timor Leste, hundreds of the ADF subjects initiated legal action against Defence, reporting that they were not adequately informed of side effects and complaining of symptoms such as depression, paranoia, and suicide ideation. When this story was first reported in the media in 2004, ADF Surgeon General Tony Austin initially claimed that the number of personnel involved in these trials was in the “dozens rather than hundreds”, however Chief of Army Peter Leahy admitted several days later that the actual number of trial subjects in Timor Leste was 1,351. The legal action was discontinued after the Australian government introduced legislation that would have required them to forfeit veterans entitlements in the event their claim succeeded. The majority of these veterans continue to experience chronic neuropsychiatric disorders including depression, anxiety, misdiagnosed PTSD, personality disorders and conversion disorders. Many of them were discharged from the ADF on medical grounds, now suffering debilitating side effects of anti-psychotic drugs prescribed off-label, and there have been a number of suicides.
The published study findings and other official ADF reports of these trials universally portray tafenoquine as a “safe” and “well tolerated” anti-malarial drug. As public scrutiny has intensified in recent months, senior Defence officials have insisted that serious neuropsychiatric side effects from tafenoquine are rare. However the disturbing truth is that the incidence of acute psychotic reactions and chronic neuropsychiatric illness attributable to the use of tafenoquine in these trials almost certainly meets the MedDRA definition of “common” (1-10%) or “very common” (>10%). There can be little doubt that the published findings of these trials constitute comprehensive scientific fraud, achieved in a number of ways that will be more fully documented in subsequent posts, including:
Providing false and/or misleading information to the trial subjects.
Coercing subjects into participating in the trials.
Relying on the prevailing stigma of mental health problems to minimise subject reporting of neuropsychiatric adverse effects.
Recording serious adverse events as “withdrawals” to avoid attributing them to the trial drug in the published study report.
Misattributing adverse events to extraneous causes.
Failing to include follow up medical examinations in trial protocols, to avoid recording chronic adverse effects attributable to the drug.
The relevant ethical standards for the conduct of these clinical trials are laid down in the TGA’s Note for Guidance on Good Clinical Practice, which is mandated by the National Health and Medical Research Council Act. This standard describes “members of the armed forces” as vulnerable subjects “whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.” Relevant provisions in these standards include:
“Foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society.”
“The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society.”
“During and following a subject’s participation in a trial, the investigator/institution should ensure that adequate medical care is provided to a subject for any adverse events, including those related to the trial.”
In obtaining the informed consent of trial subjects, the institution should adhere to “the ethical principles that have their origin in the Declaration of Helsinki.”
Part 2 of this series will examine the emerging evidence of misconduct in the c. 2001-2002 clinical trial of tafenoquine in the treatment of recurrent vivax malaria. Subsequent posts will address the larger prophylaxis trials. These will be updated as additional evidence becomes public.
“…British soldiers are being given a controversial malaria drug that carries a higher risk of depression, anxiety and psychosis compared to its alternatives, an inquiry heard yesterday.
Dr Frances Nichol, of drugs manufacturer Roche, admitted to the Defence Select Committee that the drug Lariam, used by the military, had worse side effects than other common anti-malarials.
She warned that the drug should not be prescribed to soldiers with pre-existing conditions. But another Roche spokesman admitted there was a ‘risk’ that military personnel might not disclose previous mental health problems to officers for fear of damaging their careers…”
Roche’s anti-Malaria drug Mefloquine (which goes under the trade name Lariam) is a Malaria drug which has been dogged by controversy for at least a decade now. Roche were sued in Ireland recently because of the neuro-toxic effects of Lariam (there was an out of court settlement).
In proceedings initiated in 1999, Mr Bryce sued Roche Products (Ireland) Ltd; a medical doctor and Executive Medical Care Ltd, trading as Grafton Street Medical Centre, for damages for allegedly failing to warn him of all of the side-effects of the drug.
Mr Bryce claimed his delay in prosecuting his action was allegedly due to poor health since having taken the drug.
Mr Bryce had claimed he took Lariam prior to his honeymoon in Kenya in 1996.
He claimed he suffered panic attacks and dizziness and his health had deteriorated after returning from his honeymoon….”
The neuro-toxic effects of Roche’s Lariam have been well documented now, however GSK are developing their own anti-Malaria drug (which has yet to be fully licensed) called Tafenoquine.
Tafenoquine is in the same class of drug compounds as Mefloquine and there has been speculation that Tafenoquine could be even more neuro-toxic than Mefloquine (Lariam).
Dr Remington Nevin has been studying the neuro-toxicity of these drugs and there seems to be a lot of concerns raised about GSK’s Tafenoquine…
After the devastation caused by GSK products such as Myodil, Avandia, Seroxat and Pandemrix I think the public have a right to be concerned when GSK claims to have made a breakthrough drug don’t you?…
Seroxat (Paxil) was marketed as a breakthrough wonder drug for the treatment of depression and anxiety in the late 90’s but it wasn’t long after that people began to realize that Seroxat was closer to a killer drug than a wonder drug…
I will be keeping my eye on GSK’s Tafenoquine…
Personally I wouldn’t touch any GSK drug with a barge pole..
“…Through post-trial research, the ADF has confirmed mefloquine can cause side effects likened to that of PTSD, including agitation, mood swings, panic attacks, confusion, hallucinations, aggression, psychosis and suicidal thoughts in a small number of patients.
But Dr Remington Nevin, a leading international expert on mefloquine and tafenoquine, told the audience via Skype that the “information in the ADF consent forms undermined critical manufacturer’s safety information and understated known risks”.
He also said ADF subjects were not given information to allow for fully informed consent, attributing both failures to soldiers “experiencing lasting harm from the drug”.
AVM Smart the forum was a “step in the right direction” and provided important dialogue to inform “the next steps”.
“It was really beneficial to be able to listen and understand the experiences of those who attended so we can work on further reducing the barriers both current and ex serving members might encounter when trying to seek help,” she said.
The Department of Veterans Affairs declined to attend the forum….”