LONDON – Over the next decade pharmacovigilance will move on from a sole focus on adverse drug reactions (ADRs) to encompass monitoring of the in-market efficacy of medicines, according to Guido Rasi, executive director of EMA.

Plans for the collection of efficacy data of marketed drugs will be agreed well before products are launched and the current binary system, in which safety and efficacy are separate concerns, will evolve to one that measures overall on-market performance of drugs, Rasi said in a forward-look to 2030, published in the journal, Clinical Pharmacology & Therapeutics.

Pharmacovigilance already is moving on from being a reactive activity that relies on spontaneous reports of suspected ADRs, to being a proactively planned process. But to move to the next level, oversight of drugs on the market needs to include both safety and efficacy.

“By 2030, for targeted new medicines, a planned monitoring of performance on the market will take place, with nearly real-time decision making by regulators to optimize safe and effective use,” said Rasi and co-authors Sabine Straus, chair of EMA’s safety committee and Peter Arlett, EMA’s head of pharmacovigilance.

The evolution of pharmacovigilance will draw on data from electronic health records (EHRs), disease registries, claims data, mobile apps and social media, and be harnessed by “radically enhanced” capabilities for collecting, integrating and analysing information.

It also will require greater collaboration between companies, regulators, health care professionals, patients and academics.

In particular, “EHRs and claims data can provide new insights in health, disease, and critically, the use and performance of medicines, including both benefits and risks,” said Rasi.

If such near real-time assessments become a reality, in-market data will feed into product labeling, health technology assessments of value, reimbursement decisions of payers and also support clinical decision making.

Despite progress in assessing and analyzing real world health data, the authors acknowledge more work is needed, of which developing a methodology for evaluating on-market efficacy is perhaps the greatest challenge.

Ensuring pharmacovigilance alerts reach the patient

Through another window in his crystal ball, Rasi foresees the EMA and other regulators engaging with patients and health care professionals “much more intensively” in order to ensure pharmacovigilance advice is acted on.

A recent review of the impact of regulators’ safety warnings found healthcare professionals do not always alter prescribing behavior in response.

One of the most egregious cases in point was the alert in 2013 indicating use of the epilepsy and bipolar drug valproate during pregnancy poses a significant threat of birth defects and developmental disorders.

Although steps were taken to inform women of the risks, the message did not get through to patients and there was a “lack of impact of [the] stringent warnings,” in terms of prescribing practice, Rasi noted.

That led EMA to put in place new restrictions, in effect banning use of valproate during pregnancy, in March 2018.

But as recently as last month, the U.K. Medicines and Healthcare products Regulatory Agency reported that although much reduced, prescribing of valproate in pregnancy is still occurring.

“There is much further to go, if we are to be truly effective in responding to patients’ needs and to enable patients to use their medicines optimally,” Rasi wrote.

Whatever the opportunities real world evidence presents for improving pharmacovigilance, Rasi said the current system of flagging up problems in individual case safety reports (ICSRs), must continue.

At the end of 2018, EMA’s Eudravigilance database of ICSRs held over 14 million case reports. Around 55% of all new drug safety issues are detected from ICSRs, and the number of products that have been withdrawn based on these reports is also high.

While there are detractors who say the ICSR is dead (or should be dead), Rasi said, “The evidence suggests ICSRs remain a very useful data source for detecting potential new safety issues.”

However, he acknowledged ICSR reporting needs to get smarter. “Our message is to protect and improve ICSRs, our main source of safety signals,” Rasi said. “The ICRS is far from dead, but it can and should be improved.”

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