The BMJ Today: Dabigatran and other new oral anticoagulants—demand the data

debsLast week, The BMJ published a series of articles that investigated how the safety and effectiveness of the new oral anticoagulant, dabigatran, had been studied, licensed, and subsequently marketed.

An investigation found that the drug company Boehringer Ingelheim withheld important analyses from the regulators, which showed that monitoring drug plasma concentrations and adjusting the dose could improve safety. Boehringer Ingelheim’s marketing strategy, however, has emphasised that unlike warfarin, there is no need for dose adjustment. “No need for regular blood tests to see if your blood-thinning level is in the right range,” boasted one of its US advertisements. Company documents revealed in the course of US litigation over dabigatran show how, with proper monitoring and changing the dose as needed, major bleeds could be reduced by 30-40% in comparison with well controlled warfarin. But neither doctors nor regulators have ever been aware of these calculations.

The BMJ posted the analyses that were withheld from the regulators, and which underpin the investigation.

In a rapid response, cardiologists Alastair Cooke and Monica Rap sum up the argument around the safety of anticoagulation. “Safety is more important than convenience,” they state, adding: “The priority should be reducing strokes and bleeding, not reducing the number of blood tests.”

They point to the nub of the issue. “Fixed dose dabigatran and other NOACs have been shown to be as effective as warfarin at reducing strokes with similar rates of bleeding. This BMJ article suggests that dose adjusted dabigatran may be significantly safer than warfarin. If this is true then it is potentially a big advance in the treatment of AF. This data should be fully published as soon as possible.”

This shouldn’t be a big ask. Indeed, Boehringer Ingelheim has only recently pledged its commitment to transparency. On 12 May 2014, the company issued a press release stating that: “Boehringer Ingelheim shows leadership by making clinical trial data available to the scientific community.”

They said that clinical study reports and other clinical documents can be requested via the following website:

Upon making the announcement, Charles de Wet, medical director for Boehringer Ingelheim UK and Ireland, said:

“Boehringer Ingelheim has always had a strong commitment to transparent research-driven innovations in medicine. The free exchange of the scientific information that underpins this is vital to safeguard this process. By going beyond our existing obligations and making our data more widely available we can help to build confidence in our company and the wider pharmaceutical industry. I feel strongly that this is the correct approach and believe it will benefit science and aid breakthroughs which will make people live longer, healthier lives.”

But should this stop with dabigatran? Shouldn’t the companies that make the other new oral anticoagulants, such as rivaroxaban and apixaban, open up their data to similar scrutiny to help doctors use the drugs in the safest possible way?

Indeed, Hugo ten Cate, medical director of the Maastricht thrombosis anticoagulation clinic and coeditor in chief of Thrombosis Journal, has been calling for such data since early 2012.

“It is critical that pharmaceutical companies take their responsibilities and provide and publish all relevant data on drug levels and coagulation test responses so that it becomes clear what the approximate therapeutic and harmful ranges of laboratory test outcomes are, for each anticoagulant agent. There is no good reason not to be transparent in these matters, even if it would entail the small risk that doctors would want to optimise therapy based on lab test results,” he said.

So, who will step up to the challenge and approach the companies to demand the data, which in the interests of patient safety, really should be made public?

Deborah Cohen is investigations editor for The BMJ.