Table 1.

Core Outcome Set Standards for Development (COS-STAD) Recommendations Applied to Ongoing Neuro-Oncology COS Projects

Domain	Standard	Methodology	The COBra Studya	COSMIC: Interventionb	COSMIC: Observationb	The COMBAT Projectc
Scope specification	1	The research or practice setting(s) in which the COS is to be applied	Later phase clinical effectiveness trials that will inform clinical decision making.	Later phase clinical effectiveness trials that will inform clinical decision making.	Clinical studies of incidental, minimally symptomatic, and untreated intracranial meningioma that will inform clinical decision making.	Routine clinical practice, individual surgeon and institution outcome reporting, and later phase clinical effectiveness trials that will inform clinical decision making.
	2	The health condition(s) covered by the COS	Intracranial glioma, both low- and high-grade.	Treated intracranial meningioma.	Incidental, minimally symptomatic, and untreated intracranial meningioma.	Primary pediatric CNS tumors observed in the pediatric population.
	3	The population(s) covered by the COS	Human adults aged 18 or above.	Human adults aged 18 or above.	Human adults aged 18 or above.	Human children aged 18 or below (although some pediatric neuro-oncology trials include patients beyond the age of 18).
	4	The intervention(s) covered by the COS	Interventions, alone or in combination, aimed at the tumor or direct effects of the tumor to include surgery, systemic anti-cancer treatments (including chemotherapy, immunotherapy and targeted therapies), radiotherapy and supportive interventions.	Interventions including surgical resection, radiotherapy, stereotactic radiosurgery, pharmacotherapy, perioperative care and supportive treatments; any of which may be in isolation or in combination with each other.	Active monitoring only as an intervention, but not treatment for an intracranial meningioma.	Interventions limited to surgical biopsy and/or surgical resection.
Stakeholders involved	5	Those who will use the COS in research/clinical practice	Clinical trialists and academic clinicians undertaking glioma trials.	Clinical trialists investigating interventions for intracranial meningioma.	Clinical trialists investigating active monitoring strategies for patients with intracranial meningioma.	Individuals, institutions, and policy makers evaluating patient outcomes, and clinical trialists investigating interventions for primary pediatric CNS tumors.
	6	Healthcare professionals with experience of patients with the condition	Multi-professional clinicians involved in glioma patient care; clinical trialists and academics involved in glioma research; policy makers and regulators.	This will include clinicians from multiple subspecialties and nonclinician healthcare professionals with active involvement in the care of patients with intracranial meningioma.	This will include clinicians from multiple subspecialties and nonclinician healthcare professionals with active involvement in the care of patients with intracranial meningioma.	This will include clinicians from multiple subspecialties and nonclinician healthcare professionals with active involvement in the care of patients with primary pediatric CNS tumors.
	7	Patients with the condition or their representatives	Persons with the condition and their family members will be included.	Patients with a diagnosis of intracranial meningioma who have received treatment will be included, along with relatives and carers of such patients.	Patients with a diagnosis of incidental intracranial meningioma who have not received treatment will be included, along with relatives and carers of such patients.	Patients with a diagnosis of a primary pediatric CNS tumor who have received surgical biopsy and/or surgical resection will be included, along with relatives and carers of such patients.
Consensus process	8	The initial list of outcomes considered both healthcare professionals’ and patients’ views.	A trial registry search and systematic literature review of glioma trial outcomes will consider healthcare professionals’ views. A systematic review of qualitative literature will identify patient and key stakeholder perceptions of important outcomes. Semistructured interviews with patients’ and caregivers will identify additional outcomes of importance based on “lived experience”.	A trial registry search and systematic literature review of intracranial meningioma trial outcomes will consider healthcare professionals’ views, whilst Patient Research Partner input and published semistructured interviews with patients will consider patients’ views.	A trial registry search and systematic literature review of clinical studies of incidental, minimally symptomatic, and untreated intracranial meningioma will consider healthcare professionals’ views, whilst Patient Research Partner input and published semistructured interviews with patients will consider patients’ views.	A trial registry search and systematic literature review of primary pediatricCNS tumor trial outcomes will consider healthcare professionals’ views, whilst a systematic literature review of patient-reported outcomes will consider patients’ views. Semistructured interviews with patients and/or their relatives and carers will contribute to the long-list.
	9	A scoring process and consensus definition were described a priori.	Participants will rate each of the outcomes on a 9-point Likert scale, (1–3, not important; 4–6, important but not critical; and 7–9, important and critical. During Round 1, participants can add outcomes they feel are missing. Votes from individuals in each stakeholder group will be given equal weighting. All original outcomes will be presented in Round 2. Outcomes added by participants in Round 1 will be presented in Round 2. In Round 2, respondents will be presented with their own rating for each outcome and how it was rated by their own stakeholder group. Based on this information, respondents will be invited to amend their score, if they wish. During Round 2, participants can rate the outcomes suggested in Round 1.	Outcomes to be scored on a 9-point Likert scale, whereby(1–3) is of limited importance, (4–6) is important but not critical, and (7–9) is critically important. Consensus defined as 80% or more of participants scoring an outcome as critical (7–9).	Outcomes to be scored on a 9-point Likert scale, whereby(1–3) is of limited importance, (4–6) is important but not critical, and (7–9) is critically important. Consensus defined as 80% or more of participants scoring an outcome as critical (7–9).	To be determined, protocol in development.
	10	Criteria for including, dropping, adding outcomes were described a priori.	The threshold for consensus for inclusion in or exclusion from the COS will be ≥ 70%, informed by those used in comparable COS development studies. After the Delphi, outcomes will be proposed for inclusion in the final COS if ≥ 70% respondents rate the item as 7–9 and ≤ 15% rate the item as 1–3. Items will be proposed for exclusion from the final COS if ≥ 70% respondents rate the item as 1–3 and ≤ 15% rate the item as 7–9. Those outcomes that do not reach agreement after the two Delphi rounds will be discussed in the consensus meeting, together with the items proposed for inclusion and exclusion.	Critical outcomes will be included.Outcomes rated as critical by only 50% or less of participants would be dropped. Outcomes to be discussed and voted on at the consensus meetings will be those that are neither included or dropped.	Critical outcomes will be included.Outcomes rated as critical by only 50% or less of participants would be dropped. Outcomes to be discussed and voted on at the consensus meetings will be those that are neither included or dropped.	To be determined, protocol in development.
	11	Care was taken to avoid ambiguity of language used in the list of outcomes.	Both study content and study materials will utilize plain language summaries and clinical explanations where necessary. All materials will be reviewed with Patient Research Partners and pilot tested with patients and healthcare professionals.	Both study content and study materials will utilize plain language summaries and clinical explanations where necessary. All materials will be reviewed with Patient Research Partners and pilot tested with patients and healthcare professionals.	Both study content and study materials will utilize plain language summaries and clinical explanations where necessary. All materials will be reviewed with Patient Research Partners and pilot tested with patients and healthcare professionals.	Both study content and study materials will utilize plain language summaries and clinical explanations where necessary. All materials will be reviewed with Patient Research Partners and pilot tested with patients and healthcare professionals.

(a) The COBra Study. COMET registration No. 1793, accessible at www.comet-initiative.org/Studies/Details/1793, and is also registered on PROSPERO (CRD42021236979). This study has Cardiff University sponsorship and Cardiff University School of Medicine Research Ethics Committee approval (Ref SMREC 21/59), and is funded by The Brain Tumour Charity (GN-000704). (b) The COSMIC Project. COMET registration No. 1508, accessible at www.comet-initiative.org/Studies/Details/1508. This study has University of Liverpool sponsorship and ethical approval (Ref UoL001601), and is funded by The Brain Tumour Charity (Jxr30103). (c) The COMBAT Project. COMET registration No. 1968, accessible at www.comet-initiative.org/Studies/Details/1968. Sponsorship, ethical approval, and funding are yet to be obtained for this project.