tetano
Editor, Senior Moderator
BMJ Open
. 2024 Apr 25;14(4):e078137.
doi: 10.1136/bmjopen-2023-078137. Swissped-RECOVERY: masked independent adjudication for the interpretation of non-randomised treatment in a two-arm open-label randomised controlled trial (methylprednisolone vs immunoglobulins) in Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) involving 10 secondary and tertiary paediatric hospitals in Switzerland
Nina Schöbi[SUP] #[/SUP][SUP] 1 [/SUP], Carlos Sanchez[SUP] #[/SUP][SUP] 2 [/SUP], Tatjana Welzel[SUP] 2 3 [/SUP], Alasdair Bamford[SUP] 4 5 [/SUP], Kate Webb[SUP] 6 [/SUP], Pablo Rojo[SUP] 7 [/SUP], Adriana Tremoulet[SUP] 8 [/SUP], Andrew Atkinson[SUP] 2 9 [/SUP], Luregn J Schlapbach[SUP] 10 11 [/SUP], Julia Anna Bielicki[SUP] 12 13 [/SUP]; Swissped-RECOVERY trial group
Collaborators, Affiliations
Objectives: In trials of acute severe infections or inflammations frequent administration of non-randomised treatment (ie, intercurrent event) in response to clinical events is expected. These events may affect the interpretation of trial findings. Swissped-RECOVERY was set up as one of the first randomised controlled trials worldwide, investigating the comparative effectiveness of anti-inflammatory treatment with intravenous methylprednisolone or intravenous immunoglobulins in children and adolescents with Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We present one approach towards improving the interpretation of non-randomised treatment in a randomised controlled trial.
Design: This is a pre-planned ancillary analysis of the Swissped-RECOVERY trial, a randomised multicentre open-label two-arm trial.
Setting: 10 Swiss paediatric hospitals (secondary and tertiary care) participated.
Participants: Paediatric patients hospitalised with PIMS-TS.
Interventions: All patient-first intercurrent events, if applicable, were presented to an independent adjudication committee consisting of four international paediatric COVID-19 experts to provide independent clinical adjudication to a set of standardised questions relating to whether additional non-randomised treatments were clinically indicated and disease classification at the time of the intercurrent event.
Results: Of 41 treatments in 75 participants (24/41 (59%) and 17/41 (41%) in the intravenous methylprednisolone and immunoglobulin arms of the trial, respectively), two-thirds were considered indicated. The most common treatment (oral glucocorticoids, 14/41, 35%) was mostly considered not indicated (11/14, 79%), although in line with local guidelines. Intercurrent events among patients with Shock-like PIMS-TS at baseline were mostly considered indicated. A significant proportion of patients with undifferentiated PIMS-TS at baseline were not attributed to the same group at the time of the intercurrent event (6/12 unchanged, 4/12 Kawasaki disease-like, 2/12 Shock-like).
Conclusion: The masked adjudication of intercurrent events contributes to the interpretation of results in open-label trials and should be incorporated in the future.
Trial registration numbers: SNCTP000004720 and NCT04826588.
Keywords: SARS-CoV-2 infection; paediatric infectious disease & immunisation; paediatric intensive & critical care; post-infectious disorders; randomized controlled trial.
. 2024 Apr 25;14(4):e078137.
doi: 10.1136/bmjopen-2023-078137. Swissped-RECOVERY: masked independent adjudication for the interpretation of non-randomised treatment in a two-arm open-label randomised controlled trial (methylprednisolone vs immunoglobulins) in Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) involving 10 secondary and tertiary paediatric hospitals in Switzerland
Nina Schöbi[SUP] #[/SUP][SUP] 1 [/SUP], Carlos Sanchez[SUP] #[/SUP][SUP] 2 [/SUP], Tatjana Welzel[SUP] 2 3 [/SUP], Alasdair Bamford[SUP] 4 5 [/SUP], Kate Webb[SUP] 6 [/SUP], Pablo Rojo[SUP] 7 [/SUP], Adriana Tremoulet[SUP] 8 [/SUP], Andrew Atkinson[SUP] 2 9 [/SUP], Luregn J Schlapbach[SUP] 10 11 [/SUP], Julia Anna Bielicki[SUP] 12 13 [/SUP]; Swissped-RECOVERY trial group
Collaborators, Affiliations
- PMID: 38670610
- DOI: 10.1136/bmjopen-2023-078137
Objectives: In trials of acute severe infections or inflammations frequent administration of non-randomised treatment (ie, intercurrent event) in response to clinical events is expected. These events may affect the interpretation of trial findings. Swissped-RECOVERY was set up as one of the first randomised controlled trials worldwide, investigating the comparative effectiveness of anti-inflammatory treatment with intravenous methylprednisolone or intravenous immunoglobulins in children and adolescents with Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We present one approach towards improving the interpretation of non-randomised treatment in a randomised controlled trial.
Design: This is a pre-planned ancillary analysis of the Swissped-RECOVERY trial, a randomised multicentre open-label two-arm trial.
Setting: 10 Swiss paediatric hospitals (secondary and tertiary care) participated.
Participants: Paediatric patients hospitalised with PIMS-TS.
Interventions: All patient-first intercurrent events, if applicable, were presented to an independent adjudication committee consisting of four international paediatric COVID-19 experts to provide independent clinical adjudication to a set of standardised questions relating to whether additional non-randomised treatments were clinically indicated and disease classification at the time of the intercurrent event.
Results: Of 41 treatments in 75 participants (24/41 (59%) and 17/41 (41%) in the intravenous methylprednisolone and immunoglobulin arms of the trial, respectively), two-thirds were considered indicated. The most common treatment (oral glucocorticoids, 14/41, 35%) was mostly considered not indicated (11/14, 79%), although in line with local guidelines. Intercurrent events among patients with Shock-like PIMS-TS at baseline were mostly considered indicated. A significant proportion of patients with undifferentiated PIMS-TS at baseline were not attributed to the same group at the time of the intercurrent event (6/12 unchanged, 4/12 Kawasaki disease-like, 2/12 Shock-like).
Conclusion: The masked adjudication of intercurrent events contributes to the interpretation of results in open-label trials and should be incorporated in the future.
Trial registration numbers: SNCTP000004720 and NCT04826588.
Keywords: SARS-CoV-2 infection; paediatric infectious disease & immunisation; paediatric intensive & critical care; post-infectious disorders; randomized controlled trial.