When a pharmaceutical company develops a new medicinal product, it conducts a series of studies to demonstrate the efficacy and safety of the medicine in certain diseases. These are called clinical trials1 and they are submitted to the regulatory authorities when applying for marketing authorisation for the medicinal product. They are a powerful tool demonstrating that a medicine “works” for a specific disease3.
In turn, the premise of a biosimilar medicine development programme is to demonstrate similarity with the reference biological medicinal product, since the benefits for patients have already been established for the latter1.
Due to their high cost3, clinical trials often focus on demonstrating efficacy and safety in a controlled environment and with a select population2. As such, many doctors feel they also need to know how best to use the medicines, whether biological medicinal products or their biosimilars, beyond the populations included in the studies2. This is where Real World Evidence comes in.
1. Beyond the clinical trial
Real World Evidence (RWE) refers to data on the use of a medicinal product obtained outside of clinical trials or the academic world3. In other words, the efficacy and safety data collected from medical records, pharmacovigilance records, personal devices or electronic health applications3 after the medicine has been marketed, i.e. during its clinical use.
Depending on their design, RWE studies may follow patients for several years, or study treatment in patients not included in clinical trials (children, elderly patients, patients with concomitant diseases, etc.) or in other indications. In other words, they can provide the safety and efficacy data that doctors need4.
2. Pharmacovigilance and risk management plans
All pharmaceutical companies that opt to market a medicinal product are required to submit a Risk Management Plan5 to the Regulatory Authorities, obliging them to:
• Establish a safety profile for the medicinal product.
• Plan how to prevent or minimise the risks associated with the medicinal product.
• Plan how to improve their knowledge on the medicinal product’s safety and efficacy.
• Measure the efficacy of risk minimisation measures.
As part of this plan, the pharmaceutical companies must conduct monitoring known as pharmacovigilance, defined by the WHO as the “science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem”6, which should focus on detecting safety problems with the medicinal product once it has been marketed.
RWE represents a variety of different strategies and monitoring activities, which go beyond passive surveillance. Its objective is to collect data from real life6. This would include monitoring of electronic health databases, observational studies, targeted clinical research and treatment records.
3. The example of Bevax®
Bevax® (a bevacizumab biosimilar) provides an example of real-life data collection. Developed by mAbxience, it has been approved in several countries with the same indications as the reference biological medicinal product. It was approved in Argentina in November 2016 and an active pharmacovigilance programme, a fundamental part of the risk management plan, was started to establish a safety profile assessing the incidence of adverse effects related to its use6.
The results of this data collection were recently published based on reports collected up to May 2018. The process consisted of reviewing treatment records of patients treated with Bevax®. The records were composed of three questionnaires6:
1. Notification questionnaire at the start of treatment with collection of data about the patient, his/her disease and details of the treatment6.
2. Five months after the start of treatment, the doctor completed the outcomes questionnaire about the course of the treatment and whether there had been any adverse effects6.
3. If adverse effects or death had occurred, the doctor had to complete the individual safety report, detailing the circumstances of the adverse effect or death6.
The results suggest that Bevax® has a safety and efficacy profile comparable to that of the reference biological medicinal product6. Although they are preliminary, these results contribute to a better understanding of Bevax® by clinicians.
Biosimilars have the potential to improve access to effective treatments at a lower cost than their reference biological medicinal products4. Doctors play an important role in adopting biosimilars in clinical practice4 and demand data beyond those obtained from the clinical trials conducted for registration purposes4. The use of Real World Evidence provides doctors with the data they need, facilitating the rational use of biosimilar medicines6.
1. Bosco JLF, Bryant A, Dreyer NA. The Current Biosimilars Landscape and Methodological Considerations for Real-World Evidence Generation. :4.
2. Sherman RE, Davies KM, Robb MA, Hunter NL, Califf RM. Accelerating development of scientific evidence for medical products within the existing US regulatory framework. Nature Reviews Drug Discovery. 2017;16(5):297-298. doi:10.1038/nrd.2017.25
3. Sherman RE, Anderson SA, Dal Pan GJ, et al. Real-World Evidence — What Is It and What Can It Tell Us? New England Journal of Medicine. 2016;375(23):2293-2297. doi:10.1056/NEJMsb1609216
4. Ronnebaum S, Atzinger C, International P. Enhancing Biosimilar Adoption With Real-World Evidence. :3.
5. Risk-management plans | European Medicines Agency. https://www.ema.europa.eu/en/human-regulatory/marketing-authorisation/pharmacovigilance/risk-management/risk-management-plans. Accessed January 18, 2019.
6. Fernández F, Deprati M, Rodríguez Acedo P, Spitzer E, Romera A, Español N. Implementing a treatment registry for a biosimilar: continuous safety surveillance of the biosimilar Bevax® (bevacizumab) in Argentina. Generics and Biosimilars Initiative Journal. 2018;7(3):111-120. doi:10.5639/gabij.2018.0703.023