Is GSK’s Tafenoquine (anti-Malaria Drug) As Dodgy And Dangerous As Seroxat (Paxil)?…
“….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.