37. Introduction to Benefit-risk assessment

All medicines carry a certain level of risk. A totally safe and still fully effective medicine does not exist. Even penicillin, which has saved millions of lives can cause severe allergies, which can be deadly.

Medicines provide therapeutic benefits (curing a disease, slowing its evolution, or alleviating its symptoms) but unfortunately, medicines also carrying risks of adverse drug reactions (ADRs).

The adverse drug reaction (ADRs) varies from minor symptoms (nausea, vomiting, and headache etc) to rare severe reactions (anaphylactic reactions, liver failure or cancer etc). 

The new chemical entity (NCE), emerge from the process of drug discovery, has been tested extensively in animals (preclinical research) and human (clinical trials) for the risk and benefit profile. 

In preclinical research, the efficacy data of NCE is obtained from the specific animal model of diseases in various species and strain of animals whereas safety data is obtained from various types of toxicological studies. The sponsor submitted the all information of preclinical studies to the regulatory authority.

A medicine is authorised to be used in humans when regulators estimate that the desired effects on the disease outweigh the undesired effects.

The risk-benefit analysis is a continuous process. 

After successful completion of all the phases of clinical trials, regulators still wish to learn more about the effect of the medicine as more patients start taking it. When more patients than expected report the same undesired events, and it can be proven that the medicine is the cause, then the regulators may revise their decision, adopt measures to diminish the risks when possible, or ultimately decide to withdraw the drug from the market if the effect is severe.

This risk benefit balance may change later once the drug is on market due to exposure of a large number of patients, concomitant medications and diseases, long-term exposure, confounding factors, and uncontrolled conditions. 

For example, the percentage of benefit is 90% and risk is 15%, when first periodic safety update report (PSUR) has been submitted. These percentages might be changed when 4th PSUR will be submitted (benefit, 80% and risk 50%). Thus, there have been many drugs which were initially found to be very successful in the number of patients but unfortunately were later found to have serious side effects, resulting in their withdrawal from the market.