This is a protocol to describe the methodology for a systematic review of clinical trials registries to identify intervention trials in the treatment of CF and map them to priorities for CF research

Kalaitzis, I.S.

Rowbotham, Nicola J.

Smith, S.J.

Smyth, A.R.

Repository@Nottingham

TITLE: A SYSTEMATIC REVIEW TO IDENTIFY HOW THE CURRENTCLINICAL TRIALS LANDSCAPE REFLECTS THE JAMES LIND ALLIANCETOP 10 RESEARCH PRIORITIES FOR CYSTIC FIBROSIS.PROTOCOLAUTHORS: IS Kalaitzis, NJ Rowbotham, S Smith*, AR Smyth*Corresponding authorSherie SmithADDRESS: Evidence Based Child Health Group, Division of Child Health,Obstetrics & Gynaecology, E Floor East Block, Queens Medical Centre,Nottingham NG7 2UH.Email: sherie.smith@nottingham.ac.ukAFFILIATION: Evidence Based Child Health Group, University of Nottingham,UKAbbreviations:JLA: James Lind AlliancePSP: Priority Setting PartnershipMDT: Multi-disciplinary TeamBACKGROUNDCF is a life limiting, autosomal recessive condition. It affects 1 in 2000-3000newborns in the European Union and 1 in 3500 newborns within the UnitedStates of America¹. Currently, within the UK around 10,000 people suffer fromCF².CF is a multisystem disorder which requires long term, specialistmultidisciplinary team (MDT) care in order to manage the many treatmentdecisions and aspects of CF disease effectively. Treatment varies from patient topatient according to the nature and severity of their symptoms and includes butis not limited to airway clearance, pancreatic enzyme replacement, dietarysupplementation, antibiotics and nebulisers.There are many uncertainties regarding Cystic Fibrosis (CF) treatment. Well-designed clinical trials should focus on questions which are important to patientsand clinicians. Recently, the first James Lind Alliance (JLA) Priority SettingPartnership (PSP) in CF was completed3, bringing clinicians, patients and carerstogether to identify the Top 10 research priorities. Now that we know whichtreatment uncertainties are most important to the CF community, we want toexamine how these priorities are reflected in the current clinical trial landscape.We aim to do this by carrying out a systematic review of the clinical trialsregistries and mapping the results to the James Lind Top ten.REVIEW QUESTIONThe review aims to identify current clinical trials on cystic fibrosis treatments andto find out how well these trials reflect the James Lind Alliance top ten prioritiesfor research.SEARCHESDatabases: PubMed; Australia and New Zealand Clinical Trials Register; EUClinical Trials register; Clinicaltrials.gov; ISRCTNDates searched: 1st January 2016 – 9th November 2017Language restrictions: only those trials published in EnglishThe terms “cystic fibrosis” and where possible “interventional” were used.Non registry studies were found by contacting relevant members of the CysticFibrosis Foundation regarding the Success with Therapies Research Consortium(STRC), CF health hub.Search strategies are in Appendix 1CONDITION BEING STUDIEDTreatment interventions for adults and children with cystic fibrosis.PARTICIPANTS/POPULATIONParticipants diagnosed with CF (through genetic testing or sweat testing) and ofany age. Studies including other conditions but where CF patients are analysedas a specific subgroup were included if they met the rest of the inclusion criteria.INTERVENTION(S)Studies of treatment interventions in CF will be included. Studies involving trialsof combinations of interventions, timings and duration of intervention andstopping interventions will also be included.Studies covering diagnosis, newborn screening or those concerning diagnostictest accuracy will be excluded as well as those concerning policy, evaluation ofthe training of physicians or organisation of care.The interventions we include will likely fall into these categories: drugsinterventions (antibiotics and CFTR modulators), behavioural interventions(supportive care etc), dietary interventions (vitamin D, fibre etc), device or webbased interventions (trackers, smartphone apps or virtual reality etc) and otherinterventions such as home monitoring and exercise for example.COMPARATOR(S)/CONTROLThe comparator will be either be a placebo, usual treatment or no treatment.TYPES OF STUDY TO BE INCLUDEDThe study type we are looking for is interventional clinical trials of treatments forCF. We will include completed and ongoing trials.CONTEXTSetting includes inpatient and outpatient treatments in primary and secondarycare and includes any trial that confers patient benefit.PRIMARY OUTCOME(S)The primary outcome is any clinically meaningful outcome which reflects patientbenefit. We expect the outcomes to fall into the following categories but this listis not exclusive: Lung Function (e.g. FEV1,FVC, Lung clearance index etc) Health-related quality of life validated measures (e.g. Cystic FibrosisQuestionnaire (CFQ) 26) Respiratory symptom outcomes (e.g. Respiratory and Systemic SymptomsQuestionnaire RSSQ) Hospitalisation (e.g. number of nights inpatient) School/Work attendance (e.g. number of days missed) Nutrition & Growth (e.g. weight gain, height, fat) Radiological (e.g. bone mineral density) Sputum properties Pulmonary exacerbations (measured by frequency of exacerbation or time tonext exacerbation etc) Antibiotic use (e.g. number of courses, combinations, delivery method) Adverse effects (toxicity & allergy, microbiology, complication of delivery) Exercise tolerance Sweat chloride as a measure of CFTR function Mucus clearance Nasal symptom scores Bowel symptoms (e.g. stool frequency, abdominal pain etc) Treatment burden Treatment adherence CostSECONDARY OUTCOME(S)There are no secondary outcomesDATA EXTRACTIONElectronic search results will be collated into an Excel document. Studies foundthrough other searches will be assembled into a separate Excel document.Where possible, data on study title, recruitment, intervention, outcomemeasures, sponsor/collaborators/funding and study type will be recorded in theExcel Document.For all studies, duplicates will be checked for manually and excluded.The title/abstract of each study will be scanned by one reviewer and trials thatare not interventional will be excluded. A second reviewer will check thoserecords where there is uncertainty.Studies which are deemed to fulfil the inclusion criteria from the title andabstract will be retrieved in full and scanned again for inclusion. Trials excludedat this stage will be listed with the reason for exclusion.Data will be collected on the trial characteristics, the sponsor of the trial and thefunding source.STRATEGY FOR DATA SYNTHESISThe primary aim of the review is to match the identified clinical trials with thetop ten priorities for research in CF which were the result of a James LindAlliance Priority Setting Partnership.All available information on the trials will be reviewed in order to extract themain aims of the trial and to make a decision on the most accurate match ofeach study to the Top 10 research priorities. Matching will be recorded in Excel.A second reviewer will check the matching decisions (NR) to ensure matchingresults are as accurate as possible. Any trials with matches made to the Top 10priorities deemed by the first reviewer to be uncertain and needing a secondopinion will be flagged. A final decision will be made by discussion.ANALYSIS OF SUBGROUPS OR SUBSETSMatching of trials to the James Lind Alliance top ten will be done for each priorityin turn.DISSEMINATION PLANSWe intend to publish the results in a peer reviewed journal and present at theEuropean CF Society meeting.KEYWORDSCystic fibrosisSystematic reviewPriority settingClinical trialThematic analysisREFERENCES1. Mayer-Hamblett N, Boyle M, VanDevanter D. Advancing clinical developmentpathways for new CFTR modulators in cystic fibrosis. Thorax 2016;71(5):454-61.2. Rowbotham NJ, Smyth AR. The patient voice in research - Supporting actor orstarring role? Journal of cystic fibrosis 2017;16(3):313-14.3. Rowbotham NJ, Smith S, Leighton PA, et al. The top 10 research priorities incystic fibrosis developed by a partnership between people with CF andhealthcare providers. Thorax 2017.APPENDIX 1Search strategies used in the systematic reviewClinicalTrials.govCondition or disease: 'cystic fibrosis', Study Type: 'Interventional Studies', Firstposted: '01/01/2016' to '09/11/2017'ISRCTNCondition: 'cystic fibrosis', Date applied '01/01/2016' to '09/11/2017' andOverall trial start date '01/01/2016' to '09/11/2017'EU CLINICAL TRIALS REGISTERSearch term 'cystic fibrosis', Date range '2016/01/01' to '2017/11/09'Pubmed'cystic fibrosis' in title/abstract, Date- Publication '2016/01/01' to '2017/11/09'Article types: 'Clinical trials'(cystic fibrosis[Title/Abstract]) AND ("2016/01/01"[Date - Publication] :"2017/11/09"[Date - Publication])ANZCTRSearch term 'cystic fibrosis', Study type: 'Interventional', Trial start date'01/01/2016' to '09/11/2017' and registration date '01/01/2016' to'09/11/2017'

A systematic review to identify how the current clinical trials landscape reflects the James Lind Alliance top 10 research priorities for cystic fibrosis

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A systematic review to identify how the current clinical trials landscape reflects the James Lind Alliance top 10 research priorities for cystic fibrosis

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