Waiting a minimum of 15 months is not only harming patients, it’s putting lives in jeopardy and all for the sake of adhering to ‘The Code’. For many years the interaction of the pharmaceutical industry with the medical profession has been undergoing a transition. In the past, there were inappropriate excesses in promotion of pharmaceutical […]
Waiting a minimum of 15 months is not only harming patients, it’s putting lives in jeopardy and all for the sake of adhering to ‘The Code’.
For many years the interaction of the pharmaceutical industry with the medical profession has been undergoing a transition. In the past, there were inappropriate excesses in promotion of pharmaceutical products that brought the pharmaceutical industry and health professionals into disrepute.
There was the potential for patients to lose faith in the industry and the objectivity of health professionals was questioned. The Code of Conduct (the Code) has served to re-align this relationship and restore integrity. But has it gone too far? Are the current provisions of the Code inhibiting the dissemination of up-to-date relevant information to health professionals? Could compliance with the Code potentially be costing the lives of patients in Australia?
The first principle of the Code states that “The healthcare and well-being of patients are the first priority for pharmaceutical companies”. However, the dissemination of the results of any new ground-breaking clinical trial that could improve the healthcare and well-being of patients is constrained because the Code states that “it is fundamental that any claim made must be consistent with the Australian Product Information document, irrespective of the source on which the claim is based”.
And therein lies the problem. Any recent clinical trial which improves the healthcare or well-being of patients that may be published in a prestigious journal, reviewed by acknowledged experts in the field, presented at international scientific meetings and subject to vigorous peer review cannot be discussed in any promotional activity until the product information document (PI) is updated. This would be appropriate if the PI was a dynamic online document that could be rapidly updated to reflect relevant new, important clinical information. But this is not the case. The PI is an unwieldy document that requires an expensive submission to the Commonwealth Health Department to be changed; this process takes a minimum of 15 months.
Two recent clinical trials exemplify the situation. The non-statin agent ezetimibe is available on the pharmaceutical benefit scheme (PBS) and reduces low density lipoprotein levels. It is indicated for the treatment of hypercholesterolaemia. A recent study, IMPROVE-IT, clearly and unequivocally demonstrated that the addition of this therapy to patients treated with statins further reduced LDL-cholesterol and importantly, decreased the absolute rate of cardiovascular disease (CVD) events, including death. This is very important information for medical practitioners and their patients to know.
But how are GPs, who manage the majority of these patients once they leave coronary care units, going to be informed about the results of this study? Do they routinely read the New England Journal of Medicine (NEJM)? There are many avenues whereby GPs may be informed about the outcome of this study including interaction with industry. Pharmaceutical representatives have a role in the ethical dissemination of this information that improves the health of patients. But the representatives of the company that owns ezetimibe, Merck Sharpe and Dohme, cannot discuss the results of this trial with GPs until the PI is updated, or else the company risks a substantial fine as the “claim” is not in the PI.
The second trial that exemplifies the problem is the outcome of the Empa-Reg outcome trial, again recently published in the NEJM. This is the first trial to show a reduction in the overall death rate of patients with type 2 diabetes treated with a blood glucose lowering agent.
The subjects in this study had established CVD. There was a very robust and highly significant 38% relative risk reduction in mortality from CVD in patients assigned to the SGLT2 inhibitor, empagliflozin.
This is a very important outcome. This is probably the most important clinical trial in diabetes since insulin was discovered. For the very first time, a hypoglycaemic therapy reduces the rate of CVD in patients with diabetes. This occurred on the background of near-optimal treatment of lipids and blood pressure. It is an extraordinary result. These patients are managed predominantly by GPs. How many patients with diabetes and CVD on metformin monotherapy will be commenced on a sulphonylurea or a DPP-IV inhibitor rather than being offered an SGLT2 inhibitor as the preferred second line therapy over the next 15 months or more?
Once again, the representatives of Boehringer Ingelheim and Eli Lilly, the co-owners of the product, cannot initiate a discussion of this trial with GPs until the PI has been updated. This seems even more incongruous given that the drug is now subsidised by the PBS for use in combination with metformin. This trial should give confidence to GPs and specialists concerning the use of empagliflozin and perhaps other SGLT2 inhibitors to reduce the high rates of premature death in patients with diabetes and CVD. However, pharmaceutical industry representatives of these companies cannot initiate a discussion of this trial with health professionals at this time.
The constraints imposed by compliance with the Code on pharmaceutical representatives and health professionals who present at promotional meetings is impeding the dissemination of the latest clinical information and this could be preventing the lives of patients being saved in Australia. The Code should be modified so that the overarching principle is the health and well-being of patients and not the adherence to the PI, a document that at best is 15 months out of date. This would enable the rapid and ethical communication of important new clinical data to health professionals and improve the management of patients.
Michael d’Emden is an Associate Professor at the University of Queensland and Director of Department of Endocrinology and Diabetes at the Royal Brisbane and Womens Hospital.
Conflict of interest disclosure: Professor d’Emden was the principal researcher on the Empa-Reg outcome trial and has been on the national advisory boards and received support for attending conferences or honoraria for presenting at meetings from Eli Lilly, Boehringer Ingleheim, Novartis, Merck Sharpe and Dohme, Pfizer, Bristol Myers Squibb, Astra Zeneca, Novartis, Abbott and Novo Nordisk
