Measuring Clinical Severity in Infants with Bronchiolitis

Bronchiolitis is a viral lower respiratory tract infection of infancy and a major cause of infant morbidity. Respiratory syncytial virus is the most common cause of bronchiolitis. The majority of infants infected with bronchiolitis will have mild symptoms, lasting up to five days with the infant being successfully managed at home. However, up to 3% of all infants will be admitted to hospital for supportive therapy, such as oxygen and/ or fluids. A small proportion of these hospitalised infants (10%) will rapidly deteriorate further and require critical care admission for either invasive or non-invasive ventilation. Many clinical trials have been undertaken to evaluate a number of pharmaceutical interventions used to treat bronchiolitis. However, no treatment intervention has been proven to be effective. A large proportion of these clinical trials used clinical severity scores as an outcome measure. These clinical severity scores had not undergone any rigorous development and validation as recommended by the Food and Drug Agency (FDA) when developing an outcome measure for clinical trials. This thesis sets out the psychometric methods used to develop and validate the Liverpool Infant Bronchiolitis Severity Score – Proxy Reported Outcome Measure (LIBSS-PRO). The premise of the LIBSS-PRO is two-fold. Firstly, the LIBSS-PRO has been primarily developed for use in daily clinical management to identify infant improvement or deterioration. This will contribute to the standardisation of patient care and facilitate clinical decision making. Secondly, by fulfilling the FDA criteria as an outcome measure the LIBSS-PRO will improve the quality of future clinical trials of treatment interventions for bronchiolitis. The study was divided into three phases over three bronchiolitis seasons. The first phase was concerned with the development of the LIBSS-PRO. Items were identified from the literature and through stakeholder group workshops. A conceptual framework of bronchiolitis severity was developed. Consensus methods were used to identify which items were considered the most important and to develop criteria for mild, moderate and severe bronchiolitis. The second phase determined the content validity of the LIBSS-PRO. The LIBSS-PRO was evaluated by a range of health care professionals working in a variety of clinical environments by applying the score to eligible infants. Cognitive interviewing of health care professionals was used to assess comprehension and interpretation of each section of the LIBSS-PRO. Finally, in phase three, clinical field testing was undertaken in a variety of clinical locations by health care professionals to establish construct and criterion validity and reliability of the LIBSS-PRO. Responsiveness to change and cross cultural validation will be assessed in future clinical trials

Which outcomes should be used in future bronchiolitis trials? Developing a bronchiolitis core outcome set using a systematic review, Delphi survey and a consensus workshop

Objectives The objective of this study was to develop a core outcome set (COS) for use in future clinical trials in bronchiolitis. We wanted to find out which outcomes are important to healthcare professionals (HCPs) and to parents and which outcomes should be prioritised for use in future clinical trials.Design and setting The study used a systematic review, workshops and interviews, a Delphi survey and a final consensus workshop.Results Thirteen parents and 45 HCPs took part in 5 workshops; 15 other parents were also separately interviewed. Fifty-six items were identified from the systematic review, workshops and interviews. Rounds one and two of the Delphi survey involved 299 and 194 participants, respectively. Sixteen outcomes met the criteria for inclusion within the COS. The consensus meeting was attended by 10 participants, with representation from all three stakeholder groups. Nine outcomes were added, totalling 25 outcomes to be included in the COS.Conclusion We have developed the first parent and HCP consensus on a COS for bronchiolitis in a hospital setting. The use of this COS will ensure outcomes in future bronchiolitis trials are important and relevant, and will enable the trial results to be compared and combined

Stakeholders’ perspectives on clinical trial acceptability and approach to consent within a limited timeframe: a mixed methods study

Objectives The Bronchiolitis Endotracheal Surfactant Study (BESS) is a randomised controlled trial to determine the efficacy of endo-tracheal surfactant therapy for critically ill infants with bronchiolitis. To explore acceptability of BESS, including approach to consent within a limited time frame, we explored parent and staff experiences of trial involvement in the first two bronchiolitis seasons to inform subsequent trial conduct.Design A mixed-method embedded study involving a site staff survey, questionnaires and interviews with parents approached about BESS.Setting Fourteen UK paediatric intensive care units.Participants Of the 179 parents of children approached to take part in BESS, 75 parents (of 69 children) took part in the embedded study. Of these, 55/69 (78%) completed a questionnaire, and 15/69 (21%) were interviewed. Thirty-eight staff completed a questionnaire.Results Parents and staff found the trial acceptable. All constructs of the Adapted Theoretical Framework of Acceptability were met. Parents viewed surfactant as being low risk and hoped their child’s participation would help others in the future. Although parents supported research without prior consent in studies of time critical interventions, they believed there was sufficient time to consider this trial. Parents recommended that prospective informed consent should continue to be sought for BESS. Many felt that the time between the consent process and intervention being administered took too long and should be ‘streamlined’ to avoid delays in administration of trial interventions. Staff described how the training and trial processes worked well, yet patients were missed due to lack of staff to deliver the intervention, particularly at weekends.Conclusion Parents and staff supported BESS trial and highlighted aspects of the protocol, which should be refined, including a streamlined informed consent process. Findings will be useful to inform proportionate approaches to consent in future paediatric trials where there is a short timeframe for consent discussions.Trial registration number ISRCTN11746266