Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Implementation rates of PROs/PROMs into European SmPCs of oncologic medicinal products ***

Dr. Stefanie Pektor (Abschlußjahr: 2022)

Summary
Language: English
PROs can be used as claims in product information texts to inform about the status of a patients’ health condition directly reported from the patient without interpretation of the patients’ response by a clinician or anyone else. Different kinds of PROs exist describing either a symptom, or more complex conditions like HRQL. PRO data are collected in clinical trials via PRO instruments (e.g., questionnaires or diaries) completed by the patient or completed during an interview, provided that the interviewer records only the patient’s response. As several studies suggest that especially in cancer drugs PROs may be collected during drug development in clinical trials, but are not necessarily included into the label, the aim of this master thesis was to evaluate how many oncologic drugs approved between 2016 and 2022 by EMA included PROs as endpoints into their clinical trials described in the EPAR and how many of those were implemented into section 5.1 of the respective SmPCs. For each drug, EPARs and the respective included EU SmPCs were systematically reviewed for the inclusion of PROs/PROMs, the type of PROM and the reason given by the assessors in the EPAR, why a PRO was not included into the SmPC. It was also assessed if the PRO was described as a primary, secondary or exploratory endpoint in the respective clinical trials mentioned in the EPAR and to what extend the PROs were included into the SmPC section 5.1.
Overall, the inclusion rate of PROMs from the EPAR into the respective SmPC of oncologic medicinal products approved in the EU from 2016 until today is low. For the adult indications 25% (23.4% as secondary endpoint, 1.6% as exploratory endpoint) of the PROMs mentioned in the EPARS were finally included into section 5.1 of the SmPC. For the paediatric indications the situation is even worse. Only 16.6% were included as label claim into the SmPC. Furthermore, even if PROMs were included into the SmPC, they were only included partially. This means that in the EPARs several PROMs were described, but not all of them have been approved as a label claim in the SmPC or several scores retrieved from the questionnaires were summarized as “HRQL”.
The reasons for the non-inclusion of claims derived from PROMs which have been mentioned in the assessment reports are diverse and include: inappropriate study design, no statistical significance, missing data, lack of compliance with protocol, limited quality of data, and use of an inappropriate PROM.
Although one quarter (25%) of adult PROMs mentioned in EPARs have been included as label claim into the SmPC, there is still room for improvement. For the paediatric indications only 16.6% of the PROMs have been included into the SmPC. Those results point at the need for the development of new guidance, especially on paediatric PROs/PROMs and how they should be designed and used to strengthen the likelihood of incorporation of a PRO-related claim into the label to ensure that also the paediatric patients’ voice is heard in order to enable more patient-focused clinical trial designs in the future.
Pages: 41,
Annexes: 3, Pages: 72