Sunday, March 06, 2011

Millions of surgery patients at risk in drug research fraud scandal

I wish I could believe that this is an isolated incident. But the fact is that he was only caught because he was a very lazy fraud

Professor Dr. med. Joachim Boldt above

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.

Experts described Mr Boldt's alleged forgeries as possibly the biggest medical research scandal since Andrew Wakefield was struck off last year for falsely claiming to have proved a link between the MMR vaccine and autism.

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by six British medical groups including the Association of Surgeons and the Intensive Care Society, were being withdrawn last night.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"We have withdrawn the guidelines from our website and we will need to rewrite the article," he added.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.

"Some people are comparing this to the Andrew Wakefield scandal. What Wakefield did had terrible implications on children's lives, and the principle of this is the same." 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.”


'May cause drowsiness' too confusing for modern medicine labels

Warning labels on medicines should be simplified because words such as "drowsiness" and "avoid" are too confusing for modern patients, experts claim.

Research by the British National Formulary (BNF), which advises doctors, nurses and pharmacists, found labelling that has been around for decades is now too difficult for members of the public to understand.

It found phrases such as "may cause drowsiness" are no longer "readily understood" and should now be simplified to say "this medicine may make you sleepy".

Likewise, the phrases "avoid alcoholic drink" and "take at regular intervals" caused indecision among modern takers.

The report recommends the labels should now read "do not drink alcohol while taking this medicine" and "space the doses evenly throughout the day".

The research was carried out by Professor Theo Raynor, and colleagues at the University of Leeds. He said: "Most medicines do contain leaflets which provide detailed information for patients.

"However the leaflet may get lost, which means that the label on the medicine plays a very important part in guiding people's behaviour. "It is vital therefore that wordings on labels are simple and straightforward."

Prof Raynor's team tested a selection of instructions on almost 200 people aged 20 to 80.

The experts reworded phrases that people found confusing, and then retested them in several sittings, including one-to-one interviews.

Prof Raynor said "avoid alcoholic drinks" was a good example. "Our user tests have shown that the word "avoid" can cause confusion and that some people think it only means they should limit their alcohol intake. "This phrase will now be replaced by the instruction: 'do not drink alcohol while taking this medicine', which is far clearer."

Other recommendations include changing "do not take indigestion remedies at the same time of day as this medicine" to "do not take indigestion remedies two hours before or after you take this medicine".

Another phrase, "do not stop taking this medicine except on your doctor's advice", becomes "warning: Do not stop taking this medicine unless your doctor tells you to stop."

The revised phrases are included in a new, updated version of the BNF.

"The software used by large pharmacy chains and independent pharmacist to print instruction labels is updated regularly, so we would expect to see these new phrases appear within the next six months," Prof Raynor said.

Professor Nick Barber, a pharmacologist at London University, said: "When serious errors occur which cause harm to patients, it is often as a result of a series of minor failures at various stages.

"Therefore in taking more care about the wording of detailed instructions we can help improve the safety of medicines.

"With two million prescriptions being issued every day, a small percentage improvement through labels being more understandable could make a significant impact".

Duncan Enright, publishing director at BNF publications, said: "It has never been easier to change labels on medicines given current computerised systems and therefore we hope that the large pharmacy chains and independent pharmacies will adopt these recommendations."

The words "drowsiness" and "drowsy" are thought to date back to 1520 probably from the word drusan or drusian "to sink," also "become languid, slow, or inactive" which are related to dreosan "to fall".


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