Core Outcome Measures in Effectiveness Trials

Core Outcomes for Twin-Twin Transfusion Syndrome

General Information

Summary:
Twin-Twin Transfusion Syndrome (TTTS) is a serious condition exclusive to monochorionic twin pregnancies whereby unbalanced transfusion across placental vascular anastomoses leads to hydrostatic differences between the twins. It is defined as the presence of a monochorionic-diamniotic pregnancy with oligohydramnios in one amniotic sac and polyhydramnios in the other.In more advanced stages, intervention is usually recommended to increase the chance of survival of at least one twin. MC twins have a higher risk of perinatal mortality compared to dichorionic pregnancies and singleton pregnancies and this is likely to be as a consequence of conditions of shared placentation such as TTTS. Studies have consistently shown a 3-fold increase in fetal loss and between 16 and 22 weeks gestation (when the risk of TTTS is greatest) this is as high as 10-fold. In severe early onset TTTS the mortality rate is 90% if untreated.

Given the high potential for mortality and morbidity in TTTS, there is a need for robust guidance on the safest course of management. With the advent and ongoing development of new therapeutic techniques this is more important than ever. Literature to date reports on many different outcomes, making it difficult to compare results.

The main aim of this study is to engage stakeholders including healthcare professionals, researchers and patients to produce, disseminate, and implement a core outcome set for TTTS.

Contributors:
Principal investigator:
Dr Asma Khalil
Reader/Consultant in Maternal and Fetal Medicine
St George's University of London

Contributors:
Dr James M. N. Duffy
NIHR Doctoral Fellow, University of Oxford

Dr Helen Perry
St George's University of London

Professor Basky Thilaganathan
St George's University of London

Mr Keith Tamba
Twin and Multiple Births Association

Further Study Information

Current Stage:
Ongoing
Date:
July 2016 - October 2018
Funding source(s):
None

Health Area

Disease Category
Pregnancy & childbirth

Disease Name
Feto-fetal transfusion
Twin-Twin Transfusion Syndrome

Target Population

Age Range
16 - 55

Sex
Female


Nature / type of Intervention
Any

Method(s)

Consensus meeting
Delphi process
Survey
Systematic review

Prospective Registration
This study has been registered with the International Prospective Register of Systematic Reviews (PROSPERO). The registration number is CRD42016043999. which aims to bring together researchers committed to the development and application of agreed standardised sets of outcomes. We will follow guidance set out by the PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions for the systematic review.24

Ethical Review
The National Research Ethics Service (NRES) has advised that ethical approval is not required for the Delphi survey as it is considered a service evaluation.

Steering Group
An international steering group comprising of healthcare professionals, researchers and patient representatives will be formed to oversee the development of this core outcome set.

Scope of the core outcome set
This core outcome set will apply to all therapeutic interventions for TTTS. This will not be limited by type of intervention, setting in which given or gestation at which given. TTTS will be defined as a monochorionic-diamniotic pregnancy with oligohydramnios in one amniotic sac and polyhydramnios in the other.1 We are not seeking to reach consensus on the standardisation of other aspects of study design or the definition or staging of TTTS.

Identifying potential core outcomes
We will conduct a systematic review (CRD42016043999) to identify what outcomes have been reported previously. We will search the Cochrane Central Register of Controlled Trials (CENTRAL) as well as EMBASE and MEDLINE from inception to August 2016 to identify all trials as well as observational studies reporting outcomes following intervention for TTTS using defined MeSH descriptor terms. No data or language limits will be applied. Identified studies will be reviewed by two reviewers and any discrepancies resolved by discussion. All identified outcomes will be entered into an outcome inventory for discussion by the steering group. Following agreement, the inventory will be entered into the modified Delphi method.

Determining core outcomes
The core outcomes will be determined by using a modified Delphi method. The Delphi method is a long-established tool for achieving a convergence of opinion on a particular subject by gathering data from respondents with expert knowledge of that particular subject. It allows consensus-building by using a series of questionnaires to extract opinion from participants. Web-based Delphi tools facilitate international data collection and are largely considered acceptable the user.25, 26
All stakeholders including health professionals (obstetricians, neonatologists, midwives, and general practitioners), researchers and patients will be invited to participate. We will aim to recruit 18 participants from each stakeholder group. The Delphi method will follow the following process:

Round one
All participants will be invited to register with the online survey and will be allocated a unique identifier to enable annonymisation of their responses. They will be asked to score individual outcomes on a nine point Likert scale anchored between one (labelled ‘of limited importance for making a decision’) and nine (labelled ‘critical for making a decision’). This scale was devised by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group to facilitate the ranking of outcomes according to their importance and has been adopted widely by core outcome set developers.27 There will also be an opportunity for participants to suggest new outcomes and these will be considered by the steering group for incorporation into the second round survey.

Round two
All outcomes will be carried forward and participants will be able to view the responses from the whole group and individual stakeholder groups. They will be asked to rescore the outcome with this new information. This repeated reflection and rescoring promotes convergence of opinion to form consensus upon core outcomes.25 A standardised definition will be applied to this round’s results enabling core outcomes to be identified:
[1] Consensus in (classify as a core outcome): Over 70% of participants in each stakeholder group score outcome ‘critical for decision making’ (score seven to nine) and less than 15% of participants in each stakeholder group score outcome ‘of limited importance for decision making’ (score one to three).
[2] Consensus out (do not classify as a core outcome): Over 70% of participants in each stakeholder group score outcome domain ‘of limited importance for decision making’ (score one to three) and less than 15% of participants in each stakeholder group score outcome domain ‘critical for decision making’ (score seven to nine); or
[3] No Consensus (do not classify as a core outcome): Anything else.

Following this second round, the results will be reviewed by the steering group to decide if a further round is indicated.

Stakeholder Meeting
The results of the Delphi survey will be discussed in a consensus meeting that will include a range of views from participants who completed the survey. The main objective of the meeting will be to discuss outcomes not reaching consensus and approve a final core outcome set for interventions in TTTS. To ensure unbiased consensus formation amongst a group of varied participants, the steering committee will ensure that the meeting is informal, inclusive, participatory and values all opinions.

Measuring core outcomes
Once the core outcome set has been agreed and established it will be necessary to determine how they should be measured. The steering group will consider all tools for this process including the ongoing work of The Core Outcome Measurement Instrument Selection (COMIS) project which aims to develop validated tools for measuring outcomes.28 High quality outcome measures will be associated with each core outcome and the study will not advocate the use of a single outcome measure if several high quality outcome measures are identified for a single outcome. If no high quality outcome measures exist, this will be acknowledged.


Stakeholders Involved

Charities
Clinical experts
Consumers (patients)
Device manufacturers
Governmental agencies
Journal editors
Patient/ support group representatives
Pharmaceutical industry representatives
Policy makers
Regulatory agency representatives
Researchers
Service commissioners
Service providers
Service users
Statisticians

Study Type

COS for clinical trials or clinical research
Recommended outcome measures (measurement)

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