Pharmacovigilance and long-term surveillance

A Q&A with Chris Ludlam (U.K.)

The development of large surveillance projects like the European Haemophilia Safety Surveillance project (EUHASS) is the latest step in fully understanding the long-term side effects of hemophilia treatment. Dr. Chris Ludlam, of the Department of Haematology, University of Sheffield, U.K., talks about the evolution of pharmacovigilance in hemophilia and the move towards international cooperation.

Q: Why is pharmacovigilance and monitoring important?
A: “Long-term monitoring of the side effects of treatment is very important, especially when treatment is lifelong. But to be able to collect meaningful information, monitoring has to be undertaken in a systematic way. It is particularly important to know how many patients are being monitored and what are their diagnoses—and that as many as possible of the potential side effects, like anti-factor VIII inhibitors, are being detected. Monitoring for side effects is best done by the whole hemophilia team, including the patient, to make sure they are recognized and reported.”

Q: How recently has hemophilia treatment begun to focus on the potential adverse effects of long-term care?
A: “Adverse effects of treatment have been known for at least 50 years. Anti-factor VIII inhibitors were detected in the early days of animal factor VIII concentrates, and jaundice and hepatitis have been known for a long time. The United Kingdom has been systematically collecting adverse events for about 40 years.

“But it is really only in the past five years that post-marketing surveillance has become a condition of getting a licence for a new concentrate, and only for one drug for a relatively short period of time. In the past year, EUHASS has been established, and is surveying more than 18,000 patients. A scheme is run by the U.S. Centers for Disease Control in Atlanta on a small number of patients, and a much larger project is being developed by the American Thrombosis and Hemostasis Network.”

Q: How have surveying and monitoring techniques evolved? What further improvements do you see on the horizon?
A: “Until recently, the U.K., Canada, and The Netherlands have had country registers for adverse events. Next came post-marketing surveillance for a single new drug for one to two years. Now, with schemes established to collect data from large numbers of patients using many different types of concentrates, the number of surveyed patients is very likely to increase. Because hemophilia is a rare disorder, there will have to be international collaboration, leading to projects like EUHASS.”

Q: How do practitioners and patients deal with uncertainty when the surveillance data on long-term side effects is incomplete?
A: “Today, the greatest worry is an anti-factor VIII inhibitor. Then there are the ‘infective‘ risks of treatment. The risks of serious infections like HCV and HIV are a thing of the past, provided that the concentrates are manufactured properly. For plasma-derived concentrates, there is always the worry at the back of people’s minds that a new infectious agent could emerge and get into the concentrates undetected, but not produce clinical effects for a long time, as we saw with HIV, HCV, and the prion associated with vCJD.

“It’s important that practitioners, patients, and parents know how hemophilia is likely to affect them—when they are likely to bleed, and how bleeds should be treated. If they’re getting frequent bleeds, they need to understand the importance of prophylactic infusions of clotting factor concentrate. There are uncertainties about when the condition will cause difficulties due to a bleed occurring out of the blue and disrupting family plans or outings. And there is uncertainty about the side effects of treatment. It’s important for all to know what these are and how to monitor for their occurrence.”

Q: What are the next steps for long-term surveillance?
“EUHASS is open for all hemophilia centres in Europe to join, and we’re keen to have new centres in other parts of the world. Centres should join their regional schemes, and if they don’t have one, they should consider starting one!”

Chris Ludlam chaired the session on Pharmacogivilance/Surveillance held at the XXIX International Congress of the World Federation of Hemophilia, Buenos Aires, Argentina, July 10-14, 2010. Other speakers included Mike Makris (U.K.) and Mark Weinstein (U.S.A.). Their state of the art paper, published in a special supplement of the WFH’s official journal Haemophilia, is available here.

Last Updated September 2010