Quantifying the true effect of a drug on the population goes beyond looking at the short-term results of clinical trials, says doc

A Sydney cardiologist has pointed out the importance of looking at real world evidence when examining the effects and safety profile of drugs.

“Randomised clinical trials (RCTs) look at short-term safety; it’s just for the duration of the trial,” says Professor Sindone, who is Director of the Heart Failure Unit and Department of Cardiac Rehabilitation at Concord Hospital, NSW.

“Real world evidence reaffirms and validates RCTs and clinical observations. It either confirms the results of the RCTs or makes you think twice about them.”

Professor Sindone, who gave a talk on real world evidence last month, explains that the approach has become more popular after post-marketing surveillance of some popular drugs revealed serious adverse events.

For example, a Roche hypertension drug was found to increase mortality—even though it had been on the market for 18 months.

Retrospective data has shown that digoxin increases mortality compared to propensity-matched patients.

And there is the case of diabetes medicine Avandia, which was on the market for four to five years before it was found to increase myocardial infarction.

“After that date, every diabetes drug had to go through a mortality trial to show it didn’t kill you,” he says.

“To be scientific, you don’t just put someone on medication and say, ‘there you go’. You need to follow it up and make sure you’re not doing any harm,” says Professor Sindone.

Pharmacists have a really important part in adding to real world evidence studies, he adds.

“Patients are more likely to go back to the pharmacist to ask about symptoms, adverse events. These should be reported and recorded.

“They shouldn’t tell the patient to stop the medication, but be referred to go back to the doctor or say, that’s really strange, that’s not usually an adverse effect with that medication.

“A lot of people get taken off medicines are also mistaking an adverse event to a drug when it’s something else. You should be thinking about what else is going on,” says Professor Sindone, pointing to examples such as myalgia and muscle aches with statins.

“It’s important for pharmacists to not just tell patients not to take a medicine due to an adverse event, but to go talk to their doctor.”

Warfarin, NOACs and real world evidence

There is a need to look at real world evidence in connection to new oral anticoagulants (NOACs), says Professor Sindone.

Atrial fibrillation (AF) is the biggest risk factor for stroke – and in two-thirds of stroke patients, the event was due to AF.

Meanwhile, almost one quarter of those with AF don’t know they have it, and 85% of patients with AF are not adequately anticoagulated.

“In the NOAC world, there’s a lot of inappropriate dosing. There are two risks: stroke and bleeding,” says Professor Sindone.

“Most doctors are scared of bleeding and will underdose – this will give the patient enough to have some effect but not enough to prevent stroke.

“If you ask the patients, most are more scared of having a stroke than of bleeding.”

Professor Sindone says clinical trials have found the NOAC rivaroxaban (Xarelto) leads to a 21% reduction in stroke compared to warfarin.

And real world data shows positive results for the safety profile of rivaroxaban the complements clinical trial findings.

“NOACs have been shown to have similar and maybe superior stroke prevention to warfarin,” he says.

These results have been found in RCTs, with real world evidence reaffirming its efficacy and safety profile.

Professor Sindone reminds pharmacists to be aware that there are risks and benefits to weigh up with NOAC use.

“If someone comes to the pharmacy who has bruising and bleeding because they’re on anticoagulation drugs, remind them of the risk of stroke,” he says.

“[However ultimately] it’s the doctor’s job to explain why they are prescribing a certain medication.”

Disclosure: Professor Sindone has received honoraria, speaker fees, consultancy fees, is a member of advisory boards or has appeared on expert panels for: Alphapharm, Aspen, Astra Zeneca, Bayer, Biotronik, Boehringer Ingelheim, Bristol Myers Squibb, Cube, CSL, HealthEd, Janssen Cilag, Menarini, Merck Sharp and Dohm, Novartis, Pfizer, Roche, Sanofi, Servier and Vifor.