EMA Tackles Tricky Business Of Defining Therapeutic Indications
Inconsistent Wording Makes Things Challenging For HTA Bodies And Payers
Executive Summary
The European Medicines Agency has identified key elements that regulatory reviewers should consider when evaluating the therapeutic indications proposed by companies.
The European Medicines Agency has issued advice to help regulators adopt a more consistent approach to defining therapeutic indications for medicines and address the concerns that health technology assessment (HTA) bodies and payers have expressed about incongruities on this front.
In guidance published on 21 October, the EMA seeks to ensure that the wording of therapeutic indications is consistent across products. The guidance deals with applications for marketing authorization or extensions of indication filed under the EU’s centralized procedure. It identifies and discusses the different components that reviewers of these applications should consider when evaluating the therapeutic indications proposed by the applicant for the product's summary of product characteristics (SmPC).
The guidance was developed after concerns were raised by payers and HTA bodies that use the therapeutic indication as the starting point for assessing the relative effectiveness of a medicine and making recommendations on pricing and reimbursement. They said that inconsistent wording and varying levels of detail in the indication created challenges for them.
For example, payers have observed a trend towards less specified populations being covered by the approved labeling, which leads to problems when making reimbursement decisions, according to a slide presentation from an EMA meeting with the payer community.
Other areas of the SmPC that payers said were lacking in clarity included the product's place in therapy (eg, first line, second line) and whether it is used as monotherapy or combination therapy.
Multidimensional Analysis
The new guidance focuses on the therapeutic indication of a medicine in section 4.1 of the SmPC.
The EMA notes that defining the therapeutic indication is not straightforward and requires a multidimensional analysis of aspects that influence the benefit/risk assessment.
To facilitate a consistent approach when deciding on the wording of the therapeutic indication, the guidance identifies and discusses different components that should be considered. These include defining the target disease/condition and the target population in a way that is well recognized in clinical practice.
It is also crucial to consider whether or not the benefit/risk balance is positive in relevant subgroups of the target population since this may influence the wording of the indication, says the guidance, which provides detailed advice on how to deal with subgroups.
The product’s place in therapy, whether it should be used as monotherapy and/or in combination with other products, and mandatory conditions of product usage are also discussed in the guidance.
“For some medicinal products, other components may be of importance which are not covered by this guide,” the EMA says. “The exact wording of the indication, therefore, remains a case-by-case decision.”
Following an assessment by the reviewer, the final wording of the indication may be wider or more restricted than the indication initially proposed by the applicant and compared with the population studied, according to the guidance.
The scientific basis for and reasoning behind the final wording of the indication should be clearly documented in the assessment report of the EMA's drug evaluation committee (CHMP), namely the benefit/risk section, the agency says. “In particular, if an established positive benefit/risk balance in the studied population is extrapolated to subgroups for which data are scarce or absent (ie, the indication will be broader than the study population), this should be clearly justified. This is equally important if the target population identified by the indication is more restricted compared to the study population.”
While the guidance focuses on the therapeutic indication in section 4.1 of the SmPC, the EMA says that “further guidance may also be developed through continuous reflection with stakeholders.”