Benefit-risk of medicines post approval

When a medicine is approved, the information on benefit-risk is the best information available at that time. The clinical trials performed and documented may have traditionally included a few thousand patients. Adverse drug reactions (ADR) are reported during the clinical trials. Benefit-risk is assessed and information on ADRs must be described in the product information to doctors and patients.

How can you identify more rare side effects? If the frequency of the rare side effect is 1 in 10,000 patients or maybe even 1 in 100,000 patients, it is not likely that such effects will be seen in a clinical trial with only 2,000 patients. In fact, for statistical reasons, a trial with 30,000 patients is required to observe one ADR of an occurrence of 1 in 10,000. For more information on statistics, please look at the Statistics course in the Clinical Development Module.

You could say that the ‘final clinical trial’ does not take place until the new medicine is available on the market and is prescribed to a very large number of patients. Therefore, you need a procedure to ensure that the occurrence of new ADRs is carefully reported after a medicine has been approved.

The legislation has precise requirements for doctors and for the pharmaceutical industry in this respect.

  • The doctor must report all (suspected) side effects on new medicines to the regulators.
  • The information is also given to the pharmaceutical company. The company shall, on a regular basis, analyse the degree of occurrence of side effects.
  • The benefit-risk ratio must be re-evaluated on an on-going basis.

The patient plays a very important role in supporting this process. Whenever treated with a medicine, particularly new medicines, the patient should tell the doctor about any possible side effect experienced. Only with the participation of patients, the surveillance of possible adverse reactions (ADRs) can be complete.

An important means to follow the occurrence of new ADRs is the Periodic Safety Update Report (PSUR) system:

  • The pharmaceutical company must submit a PSUR every six months during the first two years a new medicine is on the market.
  • In the PSUR, any new ADRs must be reported and evaluated.
  • The PSUR should conclude if the benefit-risk ratio is affected by new knowledge of the benefits and side effects of the medicine.

The legislation contains the means for monitoring medical treatments for new ADRs. This is covered in the pharmacovigilance legislation.