Patient-important outcomes and core outcome sets: increased attention needed!
2019; Elsevier BV; Volume: 122; Issue: 4 Linguagem: Inglês
10.1016/j.bja.2019.02.007
ISSN1471-6771
Autores Tópico(s)Hip and Femur Fractures
ResumoIn this issue of British Journal of Anaesthesia, Barnes and colleagues1Barnes J. Hunter J. Harris S. et al.Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: infection and sepsis.Br J Anaesth. 2019; 122: 500-508Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar present consensus definitions of standardised end points in perioperative medicine for infection and sepsis. The authors, an international group of experts and trialists in perioperative medicine, undertook a systematic review of the literature to identify reported outcome measures related to infection or sepsis in clinical trials in the perioperative period. Of 1857 articles retrieved, 601 were scrutinised, and a total of 255 articles underwent outcome measure extraction. The extracted outcome measures (including outcome measures not reported but suggested by authors) were rated as critical, important, or of limited importance,2Guyatt G.H. Oxman A.D. Kunz R. et al.GRADE guidelines: 2. Framing the question and deciding on important outcomes.J Clin Epidemiol. 2011; 64: 395-400Abstract Full Text Full Text PDF PubMed Scopus (1140) Google Scholar and prioritised by the authors according to relevance using the Delphi method.3Sinha I.P. Smyth R.L. Williamson P.R. Using the Delphi technique to determine which outcomes to measure in clinical trials: recommendations for the future based on a systematic review of existing studies.PLoS Med. 2011; 8: e1000393Crossref PubMed Scopus (531) Google Scholar Outcomes adjudicated as critical were subsequently rated and prioritised by the Standardised Endpoints for Perioperative (StEP) trials working group4Myles P.S. Grocott M.P. Boney O. Moonesinghe S.R. COMPAC-StEP GroupStandardizing end points in perioperative trials: towards a core and extended outcome set.Br J Anaesth. 2016; 116: 586-589Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar according to their validity, reliability, feasibility, and patient-centredness. After discussion and consensus, a total of 13 outcome measures including accompanying definitions were proposed as standardised outcomes in clinical trials in perioperative medicine within infection and sepsis.1Barnes J. Hunter J. Harris S. et al.Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: infection and sepsis.Br J Anaesth. 2019; 122: 500-508Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar The authors are to be congratulated for a very important initiative with implications for patients, relatives, healthcare systems, and society.3Sinha I.P. Smyth R.L. Williamson P.R. Using the Delphi technique to determine which outcomes to measure in clinical trials: recommendations for the future based on a systematic review of existing studies.PLoS Med. 2011; 8: e1000393Crossref PubMed Scopus (531) Google Scholar Evidence for the effectiveness of healthcare treatments should derive from high-quality randomised clinical trials or systematic reviews of trials that assess outcome measures relevant to patients5Moher D. Schulz K.F. Altman D.G. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials.Ann Intern Med. 2001; 134: 657-662Crossref PubMed Scopus (967) Google Scholar (i.e. patient-important outcomes), including pain, nausea/vomiting, quality of life, postoperative complications, and survival6Bourdaud N. Francois C. Jacqmarcq O. et al.Addition of droperidol to prophylactic ondansetron and dexamethasone in children at high risk for postoperative vomiting. A randomized, controlled, double-blind study.Br J Anaesth. 2017; 118: 918-923Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar, 7Ali M. Winter D.C. Hanly A.M. O'Hagan C. Keaveny J. Broe P. Prospective, randomized, controlled trial of thoracic epidural or patient-controlled opiate analgesia on perioperative quality of life.Br J Anaesth. 2010; 104: 292-297Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar, 8Dewinter G. Moens P. Fieuws S. Vanaudenaerde B. Van de Velde M. Rex S. Systemic lidocaine fails to improve postoperative morphine consumption, postoperative recovery and quality of life in patients undergoing posterior spinal arthrodesis. A double-blind, randomized, placebo-controlled trial.Br J Anaesth. 2017; 118: 576-585Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar, 9Calvo-Vecino J.M. Ripolles-Melchor J. Mythen M.G. et al.Effect of goal-directed haemodynamic therapy on postoperative complications in low-moderate risk surgical patients: a multicentre randomised controlled trial (FEDORA trial).Br J Anaesth. 2018; 120: 734-744Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar (Fig. 1). This is, however, rarely the case. Non-patient-centred outcomes (surrogate outcomes) are often used in clinical trials as substitutes for patient-important outcomes, including biomarkers, progression-free survival, vital signs, and radiological or histopathological examinations.10Svensson S. Menkes D.B. Lexchin J. Surrogate outcomes in clinical trials: a cautionary tale.JAMA Intern Med. 2013; 173: 611-612Crossref PubMed Scopus (95) Google Scholar In a recent systematic review, patient-important outcomes in 112 published randomised clinical trials in critically ill patients were reviewed.11Gaudry S. Messika J. Ricard J.D. et al.Patient-important outcomes in randomized controlled trials in critically ill patients: a systematic review.Ann Intensive Care. 2017; 7: 28Crossref PubMed Scopus (73) Google Scholar Only 24% of the primary outcomes and 22% of the secondary outcomes reported were adjudicated as patient-important. Mortality accounted for the vast majority of both primary and secondary patient-important outcomes, highlighting the lack of other patient-important outcomes than mortality (Fig. 1). Accordingly, patient-important outcomes should be prioritised over surrogate outcomes by trial groups, including within critical care and perioperative medicine. The reasons for using surrogate outcomes and not patient-important outcomes are multiple. In general, surrogate outcomes are easier to collect and assess, which will result in shorter trial duration, smaller size, and lower costs.12Fleming T.R. DeMets D.L. Surrogate end points in clinical trials: are we being misled?.Ann Intern Med. 1996; 125: 605-613Crossref PubMed Scopus (1352) Google Scholar Importantly, meta-epidemiological data suggest that surrogate outcomes are associated with 40–50% larger treatment effects than trials reporting patient-important outcomes.13Ciani O. Buyse M. Garside R. et al.Comparison of treatment effect sizes associated with surrogate and final patient relevant outcomes in randomised controlled trials: meta-epidemiological study.BMJ. 2013; 346: f457Crossref PubMed Scopus (122) Google Scholar This has the imminent risk that ineffective and, in worst cases, harmful treatments are used and recommended in daily clinical practice. This has been the case for several drugs,14Moynihan R. Surrogates under scrutiny: fallible correlations, fatal consequences.BMJ. 2011; 343: d5160Crossref PubMed Scopus (36) Google Scholar including hydroxyethyl starch.15Laake J.H. Tonnessen T.I. Chew M.S. et al.The SSAI fully supports the suspension of hydroxyethyl-starch solutions commissioned by the European Medicines Agency.Acta Anaesthesiol Scand. 2018; 62: 874-875Crossref PubMed Scopus (11) Google Scholar In 2010 the Core Outcome Measures in Effectiveness Trials (COMET) initiative was established to develop a standardised collection of outcomes which should be measured and reported, as a minimum, in all trials within a specific clinical area.16Gargon E. Williamson P.R. Altman D.G. Blazeby J.M. Clarke M. The COMET initiative database: progress and activities update (2014).Trials. 2015; 16: 515Crossref PubMed Scopus (28) Google Scholar The overall aim of a core outcome set is to contribute to improvements in health and social care by helping patients and the public, practitioners, and policy makers to make informed decisions about the available healthcare treatments. This is done through standardisation and harmonisation of outcome reporting in trials by identifying outcomes perceived fundamental for decision making within a specific area.16Gargon E. Williamson P.R. Altman D.G. Blazeby J.M. Clarke M. The COMET initiative database: progress and activities update (2014).Trials. 2015; 16: 515Crossref PubMed Scopus (28) Google Scholar Clinical trial groups are now increasingly developing core outcome sets within their specific clinical areas, for example within appendicitis,17Sherratt F.C. Eaton S. Walker E. et al.Development of a core outcome set to determine the overall treatment success of acute uncomplicated appendicitis in children: a study protocol.BMJ Paediatr Open. 2017; 1: e000151Crossref PubMed Scopus (13) Google Scholar acute respiratory distress syndrome,18Needham D.M. Sepulveda K.A. Dinglas V.D. et al.Core outcome measures for clinical research in acute respiratory failure survivors. An International Modified Delphi Consensus Study.Am J Respir Crit Care Med. 2017; 196: 1122-1130Crossref PubMed Scopus (198) Google Scholar cardiac arrest,19Haywood K. Whitehead L. Nadkarni V.M. et al.COSCA (Core Outcome Set for Cardiac Arrest) in adults: an advisory statement from the International Liaison Committee on Resuscitation.Resuscitation. 2018; 127: 147-163Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar and now within perioperative medicine4Myles P.S. Grocott M.P. Boney O. Moonesinghe S.R. COMPAC-StEP GroupStandardizing end points in perioperative trials: towards a core and extended outcome set.Br J Anaesth. 2016; 116: 586-589Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar including hip fracture,20O'Donnell C.M. Black N. McCourt K.C. et al.Development of a Core Outcome Set for studies evaluating the effects of anaesthesia on perioperative morbidity and mortality following hip fracture surgery.Br J Anaesth. 2019; 122: 120-130Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar renal end points,21McIlroy D.R. Bellomo R. Billings 4th, F.T. et al.Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: renal endpoints.Br J Anaesth. 2018; 121: 1013-1024Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar cancer outcomes,22Buggy D.J. Freeman J. Johnson M.Z. et al.StEP-COMPAC GroupSystematic review and consensus definitions for standardised endpoints in perioperative medicine: postoperative cancer outcomes.Br J Anaesth. 2018; 121: 38-44Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar pulmonary complications,23Abbott T.E.F. Fowler A.J. Pelosi P. et al.StEP-COMPAC GroupA systematic review and consensus definitions for standardised end-points in perioperative medicine: pulmonary complications.Br J Anaesth. 2018; 120: 1066-1079Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar and patient comfort.24Myles P.S. Boney O. Botti M. et al.Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: patient comfort.Br J Anaesth. 2018; 120: 705-711Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar Patient and public involvement is an integrated and prerequisite part in the development of core outcome sets, as this allows for nuanced assessments with a focus on patient preferences and views.16Gargon E. Williamson P.R. Altman D.G. Blazeby J.M. Clarke M. The COMET initiative database: progress and activities update (2014).Trials. 2015; 16: 515Crossref PubMed Scopus (28) Google Scholar The Standardised Endpoints for Perioperative Medicine working group4Myles P.S. Grocott M.P. Boney O. Moonesinghe S.R. COMPAC-StEP GroupStandardizing end points in perioperative trials: towards a core and extended outcome set.Br J Anaesth. 2016; 116: 586-589Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar are encouraged to consider patient and public involvement in future initiatives. In conclusion, the initiative of the StEP trials working group4Myles P.S. Grocott M.P. Boney O. Moonesinghe S.R. COMPAC-StEP GroupStandardizing end points in perioperative trials: towards a core and extended outcome set.Br J Anaesth. 2016; 116: 586-589Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar is very welcome and much needed. Along with other similar initiatives including the COMET initiative,16Gargon E. Williamson P.R. Altman D.G. Blazeby J.M. Clarke M. The COMET initiative database: progress and activities update (2014).Trials. 2015; 16: 515Crossref PubMed Scopus (28) Google Scholar this should serve as an inspiration to other trial groups within specific clinical areas. Increased attention to patient-important outcomes and core outcome sets are much needed. The author declares that they have no conflict of interest. Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: infection and sepsisBritish Journal of AnaesthesiaVol. 122Issue 4PreviewPerioperative infection and sepsis are of fundamental concern to perioperative clinicians. However, standardised endpoints are either poorly defined or not routinely implemented. The Standardised Endpoints in Perioperative Medicine (StEP) initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials. Full-Text PDF Open Archive
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