Senior Australian Army doctor accused of culpability over the deaths of tafenoquine and mefloquine drug trial subjects

Australian Army Major Stuart McCarthy in 2015

Vice Admiral Griggs cannot wash his hands of this, try as he might. The ADF caused it, to our eternal shame. The AMI and the authors of those drug trial reports—among them the ADF’s director of military medicine, Colonel Leonard Brennan—bear direct responsibility for those deaths and the legacy of widespread chronic illness among coalition troops. 

Major Stuart McCarthy, testimony to Australian Senate inquiry, 2015

IN Bougainville and Timor, army medical officers also prescribed a drug known as tafenoquine to 1512 troops, even though it had not — and still has not — been approved for use by Australian authorities.

A series of allegations have now been made about the ethics of these trials and the impact they may have had on the mental health of the participants.

One serving army officer who took mefloquine, Major Stuart McCarthy, alleges the trials were “manifestly unethical” because officers compelled soldiers to take the drug without properly warning of the risks.

He’s supported by a US expert who believes the ADF trials were “deeply unethical”.

McCarthy alleges one commanding officer of troops headed for Timor told his men they would not be deployed unless they took part in the trial, which McCarthy says amounts to compulsion.

In evidence to a Senate committee last week, McCarthy named the ADF’s director of military medicine, Colonel Leonard Brennan, as having “direct responsibility” for the chronic illness and death of Australian and allied troops. Brennan is mentioned in academic journals as having been part of the “study team” that tested tafenoquine and he has co-authored articles about the testing of both drugs on soldiers.

Source: Paul Cleary, “Drug trial a test of ethics,” The Australian, September 11, 2015

How U.S. Army officials got played by GlaxoSmithKline into subjecting 1,540 Australian peacekeeping troops to tafenoquine drug trials for commercial purposes

Walter Reed Army Institute of Research, Silver Spring MD

CONTRADICTING recent claims by Australian Defense Force (ADF) Surgeon General Air Vice Marshal Tracy Smart that a malaria outbreak during the early stages of the East Timor deployment in 1999-2000 necessitated the use of the experimental drug tafenoquine, a former WRAIR director has stated that the U.S. military was looking for large numbers of allied troops able to participate in clinical trials as part of its commercial arrangements with GlaxoSmithKline (GSK).

We essentially said: ‘We have developed [tafenoquine] to the point at which we cannot develop it any further. We need an industrial partner. You [GSK] develop it and make it available to us.’

We were completely naive, because we were desperate.

We were very mission driven, very altruistic, really babes in the woods when it came to business and such, and it showed, right? We routinely got taken advantage of, and didn’t understand the operating environment.”

FORMER WRAIR DIRECTOR, 2018

A 1998 Australian Army Malaria Institute (AMI) clinical trial in Bougainville had previously found another GSK drug, Malarone (from another drug class), to be as effective against malaria (less P. vivax eradication) and better tolerated than the existing ADF first line drug doxycycline. AMI recommended against the adoption of Malarone due to cost, less than the cost of a cup of coffee per day. Regardless, Malarone replaced mefloquine as the ADF’s second line antimalarial in 2006, when the latter drug was relegated to “drug of last resort” due to the risk of neuropsychiatric side effects. Malarone is now regarded as so safe that it is sold over the counter (without prescription) in many countries.

AVM Smart’s claim that the P. Vivax malaria outbreak most likely resulted from “drug resistance”, or “poor compliance” with the standard primaquine post exposure prophylaxis (PEP) regimen, has also been largely debunked in some of the world’s leading medical-scientific journals. Throughout the history of the use of primaquine, a significant proportion of individuals have contracted P. vivax malaria despite compliance with the recommended dose regimen. Drug failures have typically been mis-attributed to “poor compliance” or assumed “drug resistance” in the malaria parasite. However there has never been any direct scientific evidence of P. vivax resistance to primaquine. This has only ever been an assumption.

In recent years, leading malaria research scientists have discovered that the 8-aminoquinolines (including primaquine and tafenoquine) are largely ineffective because they need to be metabolised by an enzyme known as CYP2D6. Up to one quarter of the population carry a genetic deficiency which means they remain at risk of contracting malaria even if they are fully compliant with the prescribed drug regimen. In allowing the U.S. military to subject 1,540 of their soldiers to these drug trials, senior ADF officials switched from a largely ineffective but relatively safe and registered drug, to very high doses of an equally ineffective but unregistered drug which is also known to be neurotoxic.

Some time around 2010, coinciding with the publication of AMI Study 033 (the 1 RAR tafenoquine prophylaxis trial in East Timor), GSK discontinued it’s involvement in developing tafenoquine for malaria prophylaxis, ostensibly due to safety concerns for G6PD-deficient individuals. The GSK drug indicated for the treatment of P. vivax malaria, based on a single 300 mg dose sometimes called “radical cure” is known as Krintafel® in the U.S. or Kozenis® in Australia. Regulatory approval of Krintafel® by the U.S. Food and Drug Administration in 2018 entitled GSK to the award of a “priority review voucher”, a saleable product valued at up to USD$350 million, even if a single tablet of this drug is never sold.

Further background is available here and here.