Though Professor Ian Roberts, Director of the clinical trials unit at the London School of Hygiene and Tropical Medicine, had been calling for Hydroxyethyl starches (HES) fluid drips to be suspended for 15 years, it took a recommendation by the European Medicines Agency (EMA) and a review of the Commission on Human Medicines, to prompt the Medicines and Healthcare Products Regulatory Agency to issue a Class 2 Drug Alert to health professionals calling for action within 48 hours:
- Products to be withdrawn after results from large randomised clinical trials have reported an increased risk of renal dysfunction and mortality in critically ill or septic patients who received hydroxyethyl starch (HES) compared with crystalloids (simple salt solutions).
- All unexpired stock to be ‘quarantined’ and recalled to pharmacy, clinic and wholesaler level irrespective of batch number and expiry date.
In 2001 a French team published research on HES solutions in The Lancet, which concluded that the drug significantly increased the risk of kidney damage in healthy donor patients. Five years later, in 2008, Dr Christiane Hartog senior researcher at Jena University Hospital in Germany was part of another team that warned of the harms caused by HES fluids.
An online search found many entries: one was a 2013 update of a Cochrane review first published in 2010: Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function (Review), which concluded: “(A) safe volume of any HES solution has yet to be determined. In most clinical situations it is likely that these risks outweigh any benefits, and alternate volume replacement therapies should be used in place of HES products”.
These concerns were sidelined by Professor Joachim Boldt from Germany, who as regarded as a global expert on intravenous drugs. Some of his research studies were funded by some companies who made the fluids and also paid for global travels to speak at scientific conferences.
Professor Shafer, the Editor-in-Chief of the Journal Anaesthesia & Analgesia, published Boldt’s work and believes this steady stream of papers supporting starch drips – six to twelve articles every year – helped to persuade doctors to stay with the drug. Allegations were made that the wrong product was used and research was ‘done the wrong way’. Brochures were published and distributed during congresses where the critical scientists were presenting findings.
Professor Shafer spoke to Dr Boldt, whom he said had threatened him many times for damaging his reputation. Dr Boldt said he had destroyed all of the research records to protect patients and was unable to produce any evidence for the essay because that was on a machine that simply put it on a computer screen and kept no permanent records.
John Waite who presented a BBC programme on the subject reports:
- The German medical authorities found Dr Boldt didn’t have the correct ethical approvals for 88 of his reports;
- the hospital where he worked found him guilty of several instances of misconduct including using false data in at least 10 of his research reports;
- he was stripped of his professorship and scores of his papers were retracted by journals around the world.
Dr Ben Goldacre, author of Bad Pharma, is not surprised
“(R)eally I would view this as just one example of a recurring set of problems that affect the whole of medicine . . .
“(T)he whole system we have for disseminating the results of clinical trials is broken – it relies on trust and people reporting their results in often long meandering essays in academic journals that can be filled with spin”. He concludes:
“Very simply we should have all trials registered before they begin, the results shared in simple structured formats online and all data available for checking by independent researchers”.