Tepsivo's TOP 5 Ways to Make Drugs Safer

What is pharmacovigilance?

The goal of pharmacovigilance is to make drugs safer by monitoring the benefit-risk profile of the drug. Or in other words, the goal of pharmacovigilance is to protect the patients from products that are more harmful than beneficial to them. 
Monitoring the products either confirms that the product is safe in real life use or leads to a limitation of the indication of the drug or complete withdrawal from the market. Gathering information from patients and healthcare professionals helps the pharmaceutical companies to improve and refine the product information, or it can help produce new information about the drug that can ultimately be used to create a safer product. 

A lot of information can be already gathered in computer simulations, pre-clinical tests, and clinical trials before the medicinal product is approved, but information from real world is still very important. 

1. Educate patients and healthcare professionals how to use the medicinal products correctly

We looked at the number of deaths caused by ADRs and noticed that the number of deaths caused by adverse events to use of medicinal products is very low compared to the number of deaths caused by poisoning. Most likely, there are intentional overdoses among those numbers, but it seems that incorrect dosing is an issue. It is an issue that can be affected with education. 

Information about off-label use and medication errors are not gathered in authority databases (for example EudraVigilance) the same way as adverse drug reactions but the information is collected by the pharmaceutical companies for the purpose of benefit-risk monitoring. The off-label and medication information is analyzed in periodic safety update reports (PSUR, PBRER, PADER) that are submitted to the authorities. The review of the PSUR can lead to an update of the product information leaflet that is in the package with the medicine or in the educational material that is shared with the relevant healthcare professionals. In more serious and urgent situations, a Dear Health Care Provider Letter (DHCP) is distributed. Nowadays, they are often sent via email and the information is presented on a dedicated website.  

As the data is not collected in EudraVigilance, it is hard to say what the number of medication errors and overdoses compared to all individual case safety reports (ICSR) is. However, a quick keyword search into EudraVigilance 2020 data shows that approximately 4% ICSRs mention off label use, 1 % an error (medication, prescribing, storage) and 0.5 % an overdose.

2. Educate patients and healthcare professionals to recognize and report

Before 2021 and the advent of COVID-19 vaccines, most of the population has been mostly unaware of things like adverse event reporting, benefit-risk profile evaluation, or marketing authorization application and approval process. This year, we may expect roughly 200-300 % increase in ADR reports compared to 2020, based on an example data from Fimea, the Finnish regulator. In 2020, 143,958 reports were received to EudraVigilance from patients. This is approximately 10 % of all cases reported. 90 % of the reports are coming from healthcare professionals, organized collection, or literature (3 %).  

One thing is to recognize an adverse drug reaction (ADR). Many people know about the list of side-effects in the package leaflet and if they experience one of these side-effects, they will probably leave it unreported if it is not something that bothers their everyday life. For example, headache, fever, or rash would most likely not be reported unless the patient is asked by their physician or pharmacist about the treatment. 

In many countries, it is easy to report ADRs to the authorities, but only few countries have a recognizable program such as the Yellow Card Scheme in the UK. The possibility to report ADRs should be part of the training for all healthcare professionals but it should also be mentioned in the health education classes in schools. The authorities should try to advertize the possibility to report ADRs. Due to the extreme interest in COVID-19 vaccines, this possibility has become probably more evident to the patients, but it will be interesting to see what portion of the adverse events were reported to the physician or a nurse via phone call or face-to-face meetings instead of using the online forms. 

3. Make the reporting easier

It is already relatively easy to report ADRs through regulatory authority websites, but the patient still needs to know what they are looking for and needs to know about the regulatory authority. In many cases the patient might not be aware of the medicines authority in their own country let alone know that their website contains a portal for submitting information about adverse experiences with medicine. 

The regulatory authorities should make efforts to make the adverse event reporting forms easily discoverable on their websites. If the patient searches for “adverse event” in their local language, the first sites coming up on the Google search should be the authority websites explaining what adverse events are and the form to report them. 

The regulatory authorities should at least put the link to the form on their front page. It would not be a big investment to buy the domain “www.adverseevent.com” of their local language. Some regulatory authorities (for example MHRA and Saudi FDA) have gone even further than this and they have their own mobile app for reporting ADRs and other medicine and health related activities. 
It is hard to imagine a non-healthcare professional to download an app just for ADR reporting but if the app is bundled with other capabilities like reliable drug information, treatment and health advise, it could be something people downloaded. 

4. Legally required activities should have monitored metrics

As mentioned, the pharmaceutical companies are legally required to perform pharmacovigilance activities. So are the authorities. The authorities are required by the legislation to monitor the safety of the drugs in general in the country (or region). The key aspects of this are monitoring the pharmaceutical companies and looking for signals in the combined aggregate data gathered from the pharmaceutical companies. The problem is that the combination of strict legal requirements and inefficient monitoring by authorities leads to increased pharmacovigilance costs for the pharmaceutical companies. The cost is in the end paid by the patient. 

If all this was making the drugs safer, it would be acceptable. But often, the required activities have no proven effect in the safety of the drug. The regulatory authorities should be legally required to define, monitor, and act upon clear metrics and KPIs for the effectiveness of the activities. The legislative requirements should be regularly reviewed and updated based on the effectiveness of the activities. 

The goal of pharmacovigilance is to make drugs safer. So, in theory if X number of patients use a medicinal product in 2020 and they report Y amount of adverse events, in 2021 the relative number of Y should be lower. This calculation should take into consideration that hopefully more people will be aware of their possibility to report adverse events. So just reducing the number of reported adverse events is not a good thing. But then again, hopefully the population will be healthier next year meaning that there would be less of a need to use the medicinal product. On the other hand, in some countries the increase in number of drugs used might be a sign of improved access to treatment. 

That might be a bit confusing, and it is. The metrics will not be easy to create as the inability to create them (despite efforts) has demonstrated, but they should exist. 

5. PV should be a field of value-based healthcare

In addition to monitoring the effectiveness of the legislation, the regulatory authorities should be monitoring the costs of these activities. The cost of the activities should be compared to the effectiveness and thus ensured that the pharmacovigilance activities are cost effective. If a legal requirement is effective, but very expensive to fulfil, the requirement needs to be refined. Again, the idea is simple, but measuring the cost of the pharmacovigilance activities is complicated. 

The costs for pharmacovigilance activities are assumed by two parties: the pharmaceutical companies and the regulatory authorities. However, the actual payers of the costs are usually the government and the patients. To simplify even more, we all are the payers either through taxes, insurance payments, or directly. The costs related to pharmacovigilance are not easy to categorize and it gets even more difficult if we take into consideration the cost reductions that follow successful performance of pharmacovigilance activities. 

For example, with reduction of hospitalization, the pharmacovigilance activities can create value by reducing hospital days which are very expensive part of healthcare. For example, using a new, more expensive medicine, can save money if it has less serious side-effects. So, in this case, the performance of pharmacovigilance activities would end up being profitable instead of costing something. 

This is the theory behind it, but again, taking all the factors into consideration is complicated. The general rule should be that all activities should be evaluated for their effectiveness and cost. 

Discussion

These are not the only ways to make drugs safer. Research and development and innovation have a large role in shaping the future of medicine and their safety. It should also be considered, if medicinal products as we see them now, should even be part of the future of healthcare. We should be concentrating in preventive treatment, early detection methods and continuous monitoring technologies. Especially continuous monitoring through wearable technology (or implants) could be also the solution for adverse event reporting. 

Conclusion

To summarize the points we have presented above, the best ways to make medicinal products safer are:

• Educating the patients and the healthcare professionals to use the medicinal products correctly in order to reduce adverse events and especially poisoning
• Educating the patients and the healthcare professionals to recognize adverse events and how to report the adverse events
• Making it even easier to report the adverse events to the authorities
• Making it legally required to specify, monitor and act upon defined metrics for the pharmacovigilance activities
• Pharmacovigilance should be treated as a field of value-based healthcare and the activities should be adjusted accordingly