Feature: Laboratories and regulator misled over antibiotic susceptibility test discs
Editorial: Assuring the quality of diagnostic tests
One of the world’s leading producers of diagnostic tests has been falsely marketing one of their products, an investigation by the BMJ shows.
Oxoid, owned by US diagnostics giant Thermofisher, has been selling antimicrobial susceptibility test (AST) discs that do not always contain the advertised amount of antibiotic.
The $10 billion a year company’s website claims that it is “renowned for quality, accuracy, reliability and innovation.” However, internal documents seen by the BMJ show that this reputation may not be entirely justified.
They show how the company used flawed data and misled the UK regulator, the Medicines and Healthcare Products Regulatory Agency (MHRA), when concerns were raised. The company say they comply with all legal and regulatory requirements.
At worst, patients may have been prescribed the wrong antibiotic or moved from oral to intravenous treatment unnecessarily. This comes at a time when health agencies around the world are concerned about antibiotic resistance and the shortage of new antimicrobial treatments in the drug pipeline.
Only last month, the Chief Medical Officer of England, Dame Sally Davies, described antibiotic resistance as an “apocalyptic scenario”.
AST discs are used in hospitals around the world to guide the choice of antibiotic treatment. The discs, containing specified amounts of antibiotic drugs, are put onto agar jelly swabbed with a sample of the infection from a patient. A clear zone forms around discs impregnated with drugs that are effective against infection, with the size of the zone roughly proportional to the drug's activity.
Like hip replacements and breast implants, in-vitro diagnostics like Oxoid’s AST discs, must have a safety certificate. In the US, the discs are classed as medical devices and companies have to provide detailed evidence before a product can be approved for sale. But in Europe, companies can self-certify their products and say what it does without any external scrutiny.
Oxoid’s website claims that their discs are produced to “the tightest international standard” but emails seen by the BMJ suggest that accuracy may not be Oxoid’s primary concern.
Internal documents show that batches of the disc have been released that do not contain the advertised amount of drug and sometimes no drug at all. Documents also show that antibiotics were not handled as carefully as they should have been, leading to possible degradation.
The British In-vitro Diagnostic Association says that: “Using the right antibiotic is fundamental to successful treatment; using the wrong antibiotic wastes time and money, extends the period of illness and may exacerbate the emergence of resistance, endangering other patients.”
Yet when this problem was raised internally, emails show how the company “used flawed methods” which allowed them to release batches onto the market. The company deny this allegation.
Even when clinicians said they were having problems with their discs, Oxoid’s response was that they were storing their discs incorrectly.
Professor Mark Wilcox, a consultant microbiologist at Leeds Teaching Hospitals, said it would be of “great concern” if any manufacturer failed to act on reports and queries from clinicians.
In 2005, Oxoid misled the MHRA, suggesting that a recalled batch of discs had stability issues rather than admitting that one component was completely missing.
Emails seen by the BMJ suggest that employees within the company have raised issues with Oxoid’s practice, but they have been ignored. In 2009, one employee became so disgruntled with Oxoid, they contacted the MHRA with documentary evidence.
In June 2011, Professor Sir Kent Woods, chief executive of the MHRA replied to the employee, saying “I can confirm that we did correspond with the company on the basis of your allegations with a view to satisfying ourselves that the product in question complied with the regulations.”
The response has worrying implications for how well the MHRA act on concerns of employees and is happy to take companies at their word, says BMJ Investigations Editor, Deborah Cohen. As the employee put it, the MHRA has “failed in its duty to protect the public.”
In an accompanying editorial, Professor Wilcox argues that the whole system of regulating in vitro diagnostic medical devices (IVDs) needs to be improved.
There are plans to reform European IVD legislation, but he says it “remains unclear” by how much the new requirements will improve quality and, crucially, clinical utility. He believes IVD testing in designated centres “would be a step forward” in dealing with the current weaknesses, but argues that “a more comprehensive, indeed systematic, approach is needed to strengthen the current CE marking based system.”
Meanwhile users of diagnostic tests “should be particularly alert to unexplained findings and should be encouraged to report suspicious results, so that trends can be identified and investigated,” he says. He also calls for any new test to undergo a formal review “to determine its clinical utility, in a similar way that hospitals review the prescribing of a new drug.”
Deborah Cohen, Investigations Editor, BMJ, London, UK
Tel: +44 (0)7554 334 958 / +44 (0)207 383 6183
Editorial: Professor Mark Wilcox, Microbiology Department, Old Medical School, Leeds General Infirmary, Leeds, UK