Objective: To define standardised outcomes, the Core Outcome Set (COS) for reporting in studies of Intrahepatic Cholestasis of Pregnancy (ICP).
Design: e-Delphi survey and consensus process.
Setting: International.
Population: 155 individuals from Asia, Europe, Oceania, North and South America: 31 patients (20%), 121 clinicians (78%), and 3 researchers (2%).
Methods: Maternal and perinatal outcomes reported in studies of ICP were collated. Stakeholders in ICP research and clinical care scored the importance of each outcome using a 9-point Likert scale over three rounds; short-listed outcomes were ranked during face-to-face consensus meetings. The final COS was agreed by the Study Steering Committee. The study was registered prospectively with Core Outcome Measures in Effectiveness Trials. Ethical approval was granted by the King's College London Research Ethics Committee (KCL MRA-23/24-39574).
Main outcome measures: From 54 manuscripts, 97 individual clinical outcomes were attributed to ICP. Twenty three outcomes were shortlisted by the e-Delphi surveys, the ranking of which enabled selection of 10 core outcomes.
Results: Maternal core outcomes comprise: total maternal bile acid (BA) concentration (maximum), gestational age at peak BA concentration, and itch impact on maternal wellbeing. Birth core outcomes comprise: stillbirth, gestational age at birth, and spontaneous preterm birth versus induced preterm birth. Neonatal core outcomes comprise: perinatal death within 7 days of birth, perinatal asphyxia, neonatal unit admission, and mechanical ventilation.
Conclusions: Given the heterogeneity of reported outcomes, we have confirmed the need for a COS in ICP, standardising the minimum reported outcomes to reduce outcome reporting bias and research wastage.
Nadejda Capatina, William Hague, Jenny Chambers, Catherine Williamson, Caroline Ovadia
Disease Category: Pregnancy & childbirth
Disease Name: Intrahepatic Cholestasis of Pregnancy
Age Range: 0 - 100
Sex: Either
Nature of Intervention: N/A
- Charities
- Clinical experts
- Conference participants
- Consumers (caregivers)
- Consumers (patients)
- Families
- Patient/ support group representatives
- Pharmaceutical industry representatives
- Policy makers
- Researchers
- Service providers
- Service users
- COS for clinical trials or clinical research
- COS for practice
- Consensus meeting
- Delphi process
- Semi structured discussion
- Survey
- Systematic review
Stage 1:
The list of outcomes will be selected after performing a systematic review of the published literature in the field of Intrahepatic Cholestasis of Pregnancy. We will then ask participants to consent to take part in the study, and collect some basic details (name, email address, location, background), which will enable us to be in touch for follow up questions and ensure coverage across types and locations of participants. We will then ask the participants to rate how important they think a list of reported outcomes is for research studies into ICP, on a score of 1-9; if they don’t know, then they have the option to score an item a scale of 0. They can also add up to three other outcomes that they think are really important, if they have not already been included.
Stage 2:
Once we have received everyone’s responses, we will summarise how everyone else voted, and resend these to the participants by email to rescore each outcome having seen how other groups have voted.
Stage 3:
Finally, we will narrow down the list to those outcomes voted the most important, and ask the participants by email to rate this smaller list. Outcomes with >70% of participants scoring 7 to 9, with <15% scoring 1 to 3 will be included in the shortlist; those scoring <50% 7-9 in each stakeholder group will be excluded. The Study Advisory Group will decide on inclusion of any remaining outcomes.
In person stage:
This will be performed over two days, firstly with researchers and clinicians, and secondly with patients and families. Following a discussion, anonymous voting will select the Core Outcome Set; where outcomes are particularly burdensome, ranking may be required of outcomes. Definitions of the core outcomes, and how they are measured, will be agreed at the in-person consensus meetings.