Correspondence Address:
Viraj Suvarna
Medical Director, Boehringer Ingelheim India Private Limited, 1102, Hallmark Business Plaza, Gurunanak Hospital Road, Bandra East, Mumbai - 400 051
India

Full Text

Pharmacovigilance or being vigilant about drugs (safety) is not just about compliance or reporting adverse events (AEs) on time. That is a minimum mandate and ideally one should be at 100% compliance. However, for the field force this is generally an onerous task, fraught with the prospect of irritating an already irate customer.

However, looked at differently, it can be a point of engagement for a sales colleague. The adverse event reporting system can be the differentiator and a core competence. The spontaneous adverse event reporting system is a mandatory requirement for companies interested in discharging their responsibility toward their patients, for as long as their product is on the market.

The field force is trained within one month of joining. Although, it is generally a session that is driven by coercion rather than getting their buy in. What is in it for me and my business? If we answer this question to his / her satisfaction, the sales colleague will appreciate the value of AE reporting and do it willingly. When a doctor reports an adverse event, instead of getting scared s/he may not prescribe the product ever again or worse still tell other doctors not to prescribe, the sales colleague can commiserate with the doctor and inform him / her that his company has a conscientious safety department, which collects all such information and feeds back the analysis of the safety profile of the product to the real world.

The clinical safety officer thanks the doctor for honoring his / her reporting obligation and puts him / her in touch with the product physician who then proceeds to engage the reporting doctor in a conversation that enables the product physician to understand the circumstance of the case and gives an opportunity for the doctor to understand the reason behind the event. The product physician can provide data on similar events that may have occurred in India and across the globe. This way the doctor understands the event fully and the event may not have been causally related to the drug. The same could have been explained by a drug-drug interaction or perhaps the doctor may not have used the product per the label. In other words, the doctor is made to appreciate how to match the right patient to the right drug and how to use the product optimally, maximizing the benefit and minimizing the risk. The doctor is reassured of the wealth of evidence on the product's safety and tolerability, both in randomized controlled trials and in the real world, and continues prescribing the product with greater confidence. This experience improves the credibility of the company in the eyes of the customer. Continuing safety data on a product, if analyzed carefully, can reveal a whole lot of information that can help further the science around the product. At times it can lead to a new indication and a blockbuster product as happened with Viagra and erectile dysfunction. One could even conduct pharmacovigilance workshops using real life examples of the product, which can again help the business.

Reporting adverse events happens not only as a part of spontaneous adverse event reporting on marketed products. It also happens in randomized controlled trials, in the pre-marketing environment. In these trials the investigator is expected to ascribe causality of the event to the investigational drug by marking on the case report form whether the event was related, not related to the drug or that s/he is not sure. If s/he marks it as unsure, it is taken to mean that it could be because of the drug just to be on the safe side. Also, if an adverse event is reported in the 30-day period (at least five biological effect half-lives) after the last dose of the study drug, it is still ascribed to the study drug. As a result, sometimes one comes across adverse events reported in association with the use of the study drug, although the patient is no longer on the study drug. Such is the commitment of the research, ethics, and quality-based industry, which unfortunately is not commensurately appreciated by all in the medical community.

The point behind this piece is not only to showcase the heights to which the industry takes its adverse event reporting responsibility seriously, but also that the science of safety can really make all the difference to a product and the company. From a thorough analysis of the safety profile of a product, one can (and must) conceptualize risk evaluation and mitigation strategies, which comprise risk management plans and in some cases risk minimization action plans or risk MAPs. Some conscientious companies may actually inform the doctor where not to use the product (even within the label) as in those cases the risk may be more than the benefit.

For as long as the product is on the market, continuing safety evaluation, analysis, and feedback to the prescribers will help doctors understand how to use the product, how to select the right patient for the product, and how to use the product in the best possible manner, which will all help in improving the credibility of the company in the eyes of the medical community.

It is not just pharmacovigilance or pharmacodiligence, but pharmacointelligence that matters. In other words, using the information gleaned from safety reporting to not just do a causality assessment, but also to continue the benefit-to-risk evaluation, calculate disability-adjusted life-years (DALYs) gained from the efficacy and effectiveness of the product, and the DALYs lost due to its adverse event profile, or the number needed to treat versus the number needed to harm, or disproportionality analysis or even the sophisticated Uppsala algorithms such as the BCPNN (Bayesian Conditional Probability Neural Network) to differentiate noise from a signal, and scientifically determine whether a product can still remain on the market or needs to be withdrawn. Spontaneous adverse event reporting has limitations, in that, at any given point of time one is not sure how many patients have been on the drug, whether all the adverse events associated with use of the drug have been reported, and whether there is a causal relationship between the drug and event.

The Safety and Medical Affairs (SMART - Safety and Medical Affairs nothing adveRse abouT it) departments within a company can come together and be the eyes and ears of the company's processing market intelligence, in the form of spontaneous adverse events and medical information inquiries, using them to give a feedback to the product management teams, so that they are better equipped to inform doctors on the optimal usage of the product. Publishing experiential data as a case series on the use of a product in the real world, regardless of whether the product achieves a positive outcome in all the cases will also increase transparency, and guide the readers on how and where to use the product and where one may eschew the use of the product. Marketing and sales departments may only want to publish the positive experiences without realizing that this incomplete, unbalanced, selective information may mislead the doctor and eventually lead to non-usage of the product by the doctor and his / her friends through word-of-mouth adverse publicity.

To conclude, one need not shy away from reporting adverse events, but instead leverage on the fact that the science of safety can be a source of continuing business. It is not that one drug is better than another. It is about finding out which patient responds best to which drug, and which patient may not.

Continuing benefit to risk assessment helps put the product in perspective and gives the medical community a clearer picture of how to use a product in as safe a manner as possible. All of us can be patients……..even doctors.