A recent episode of File on 4, entitled “Treating Stroke: The Doctor’s Dilemma,” discusses the latest on the only clot buster for ischaemic stroke—alteplase—and touches on broader debate that will be familiar to the medical community, but less so to a lay audience.
Alteplase is currently being examined by the Medicines and Healthcare Regulatory Agency (MHRA) after retired consultant Roger Shinton raised concerns about the drug in a letter to The Lancet last summer. More recently, the MRHA panel were offered unpublished data to add to their review of the drug. On 15 June 2015, Roger Shinton, along with three other doctors, wrote to the health secretary Jeremy Hunt, highlighting ongoing concerns about the data.
In the File on 4 programme a doctor describes how the arrival of alteplase gave the medical community “something” to offer people coming through the door with ischaemic stroke. And the frank accounts of patients and their relatives showed that they wanted to try something, rather than to watch and wait.
These patients seemed to need a strong steer from medical staff to help them to make a swift decision in the middle of a medical emergency. How these patients and their relatives retrospectively viewed their decision to take the drug was determined by the outcome for them or their relative. These cases highlighted the need for clear information for doctors to share with patients and their families.
Although guidelines for prescribing the drug may offer a position for patients and doctors to work from, behind their simplicity is a complex picture. US professor David Newman who was interviewed for the programme, describes the evidence on alteplase as a jumble of data. So, two decades after the drug was first trialled, the science remains unsettled.
It was interesting to hear discussions of randomised controlled trial study design, such as baseline imbalance, and blinding, and how they might bias results in favour of the drug in the mainstream media. A recent analysis article in The BMJ describes some of the issues mentioned, and concluded that further data analysis was needed to clarify the benefits and harms of the drug.
Some of those interviewed, such as Professor Peter Sandercock who headed the IST-3 trial into the drug at Edinburgh university, seem confident in the drug. But others, including retired consultant Roger Shinton, called for a greater focus on supporting outcomes, such as mortality, place of residence on discharge, and areas of infarct on CT scan. He has also called for all the data on alteplase to be made available so they can be analysed or reanalysed. Richard Thompson, past president of the Royal College of Physicians, explained that independent statisticians and epidemiologists are needed to interpret the findings of such trials.
Beneath the specifics of the drug were undercurrents of a bigger picture. The programme’s themes, such as overdiagnosis, conflict of interest in research, guideline and regulatory panels, and access to full trial data, may be familiar to doctors and readers of The BMJ, but may be less familiar to the general public. As England’s chief medical officer Dame Sally Davies has called for a review to restore trust in the medical and research community these themes seemed particularly relevant.
Helen Macdonald is the analysis editor, The BMJ.