Patient-reported outcome measures in drugs for neurological conditions approved by European Medicines Agency 2017-2022.

BACKGROUND: Regulatory agencies have been responsive to public demand for inclusion of the patient experience in evaluating and approving therapies. Over the years, patient-reported outcome measures (PROMs) have become increasingly prevalent in clinical trial protocols; however, their influence on regulators, payers, clinicians, and patients' decision-making is not always clear. We recently conducted a cross-sectional study aimed at investigating the use of PROMs in new regulatory approvals of drugs for neurological conditions between 2017 and 2022 in Europe. METHODS: We reviewed European Public Assessment Reports (EPARs) and recorded on a predefined data extraction form whether they considered PROMs, their characteristics (e.g., primary/secondary endpoint, generic/specific instrument) and other relevant information (e.g., therapeutic area, generic/biosimilar, orphan status). Results were tabulated and summarized by means of descriptive statistics. RESULTS: Of the 500 EPARs related to authorized medicines between January 2017 and December 2022, 42 (8%) concerned neurological indications. Among the EPARs of these products, 24 (57%) reported any use of PROMs, typically considered as secondary (38%) endpoints. In total, 100 PROMs were identified, of which the most common were the EQ-5D (9%), the SF-36 (6%), or its shorter adaptation SF-12, the PedsQL (4%). CONCLUSIONS: Compared to other disease areas, neurology is one where the use of patient-reported outcomes evidence is inherently part of the clinical evaluation and for which core outcome sets exist. Better harmonization of the instruments recommended for use would facilitate the consideration of PROMs at all stages in the drug development process.

Bilateral impairment of intracortical inhibition in delayed-onset posthemiplegic dystonia: pathophysiological implications.

OBJECTIVE: To study short interval intracortical inhibition (SICI) in a rare patient with segmental dystonia of the left upper limb due to a vascular lesion in the contralateral putamen without corticospinal tract involvement. METHODS: Paired-pulse transcranial magnetic stimulation (TMS) was applied to both hemispheres in a conditioning-test paradigm. Six interstimulus intervals (ISIs) and 4 conditioning stimulation intensities were investigated in two separate sessions. RESULTS: Motor evoked potentials upon single-pulse TMS were within the normal range, whereas paired-pulse TMS revealed major changes in cortical excitability, proving that SICI was bilaterally absent. CONCLUSIONS: The bilateral impairment of SICI cannot be considered the cause of dystonic contractions, but just a predisposing factor. SIGNIFICANCE: The absence of SICI might be regarded as a condition able to promote maladaptive plastic changes triggered by focal lesions in the putamen.