Millions of surgery patients at risk in drug research fraud scandal
By Heidi Blake, Holly Watt and Robert Winnett
Millions of NHS patients have been treated with controversial drugs on the basis of “fraudulent research” by one of the world’s leading anaesthetists, The Daily Telegraph can disclose.
Joachim Boldt is at the centre of a criminal investigation amid allegations that he may have forged up to 90 crucial studies on the treatment. He has been stripped of his professorship and sacked from a German hospital following allegations about his research into drugs known as colloids.
Guidelines for British anaesthetists regarding colloids – used to boost blood volume in patients undergoing surgery – are being revised after it emerged that four of the key studies on which they were based are to be formally retracted.
Mr Boldt, 57, was regarded as a leading specialist in intravenous fluid management, and his work was published widely in British medical journals.
He claimed to have proved that colloids were as safe as other, similar treatments despite earlier studies showing them to be more dangerous. Mr Boldt’s alleged forgeries date back up to a decade.
The Consensus Guidelines on Intravenous Fluid Therapy, published by six British medical groups including the Association of Surgeons and the Intensive Care Society, were being withdrawn last night. Prof John MacFie, president of the Association of Surgeons, suggested that some British patients could have been put in danger. He said he would urge other medics to abandon colloids.
“We have withdrawn the guidelines from our website and we will need to rewrite the article,” he added. “The profession I represent does not want to be to be associated with potentially fraudulent research.
As chief anaesthetist at Ludwigshafen Hospital in the Rhineland, Mr Boldt was the leading advocate of colloids, which are now commonly used across Europe.
He published dozens of papers “proving” their benefits and contradicting studies which suggested they could increase the risk of death in surgery and cause kidney failure, severe blood loss and heart failure.
German medical authorities are scrutinising 92 of his key publications and a criminal investigation is under way into allegations that he forged documents, tested drugs on patients without their consent and fraudulently claimed payments for operations he had never performed.
Mr Boldt received funding from manufacturers of hydroxyethyl starch (HES) – the colloid he most strongly advocated – including B. Braun, Baxter and Fresenius Kabi.
He was frequently paid to speak at international medical conferences where he hailed HES as “the holy grail” of fluid drugs.
HES and other colloids are up to 10 times more expensive than the alternative fluid management drugs, crystalloids, which some experts believe are safer as they contain smaller molecules and are more easily absorbed. Mr Boldt was sacked from Ludwigshafen Hospital last November. It has established an investigating commission to review 29 of the 92 papers which have been identified as “highly suspected” of containing forged or distorted data. The others will be examined if serious evidence of forgery is found.
Prof Eike Martin, head of the investigating commission, told The Telegraph: “At first we thought that all the studies were 100 per cent invented, but now we have found a huge amount of clinical data from trials that were conducted.
“Our suspicion is that the trials are not reported accurately in the papers. Prof Boldt was an advocate for colloids and that was the conclusion of his studies, but the data he published is different from the original data we have seen.”
Prof Martin said investigators examining one study, which purported to show that HES caused less inflammation than another fluid management drug, had found that the original data contradicted the conclusion.
The editors in chief of a consortium of medical journals which published Mr Boldt’s work are also reviewing the 92 publications.
Sources close to the investigation said that the editors would announce the formal retraction of 89 papers next month.
Rhineland state prosecutors are investigating Mr Boldt over allegations that he forged the signatures of his alleged “co-authors” on his studies, conducted drugs trials without official approval and claimed money for operations that he never performed. Police raided his home and his offices at the hospital in December and seized paperwork and computers.
Lothar Liebig, the state’s director of public prosecutions, said: “Boldt published certain studies about medical drugs in order to get them accepted.
“There there is a strong suspicion that he deliberately failed to obtain the approval of the institutional review board in Ludwigshafen, which is a criminal offence.”
Other medical research has contradicted Mr Boldt’s findings.
Research by Dr Gill Schierhout and Dr Ian Roberts of University College London found in 1998 that the use of colloids during surgery increased the risk of death by four percentage points – equivalent to four extra deaths in every 100 patients.
A review published 10 years later by Konrad Reinhart and Christiane Hartog of Friedrich Schiller University in Jena, Germany cited two large-scale clinical trials which found that HES could prevent the blood from clotting, which can cause heavy bleeding. Other studies have shown that some colloids can result in complications including heart and kidney failure, fluid entering the lungs and anaphylactic shock.
Suspicion first fell on Mr Boldt in October when readers of an article that he had published in the US journal Anesthesia and Analgesia, about the benefits of HES in bypass surgery, noticed that the pattern shown by his data was “too perfect to be believed”.
Dr Rupert Pearse, a senior lecturer in intensive care medicine at Barts and the London School of Medicine, and co-author of the British guidelines on fluid drugs, said last night: “I specifically remember looking at a paper of his last year and being surprised at how lucky he had been with his results.
“For me, it shakes the world I work in and makes me feel less confident in it, and if I were a member of the public I would feel the same.”