Acessibilidade / Reportar erro

What outcomes should be evaluated in critically ill patients?

ABSTRACT

Randomized clinical trials in intensive care prioritize disease-focused outcomes rather than patient-centered outcomes. A paradigm shift considering the evaluation of measures after hospital discharge and measures focused on quality of life and common symptoms, such as pain and dyspnea, could better reflect the wishes of patients and their families. However, barriers related to the systematization of the interpretation of these outcomes, the heterogeneity of measurement instruments and the greater difficulty in performing the studies, to date, seem to hinder this change. In addition, the joint participation of patients, families, researchers, and clinicians in the definition of study outcomes is not yet a reality.

Keywords:
Patient outcome assessment; Critical illness; Critical care; Prognosis; Intensive care units

RESUMO

Estudos clínicos randomizados em terapia intensiva priorizam desfechos focados em doença e não desfechos centrados no paciente. Uma mudança de paradigma considerando a avaliação de medidas após a alta hospitalar e medidas focadas na qualidade de vida e em sintomas comuns, como dor e dispneia, poderiam refletir melhor os desejos de pacientes e de seus familiares. No entanto, barreiras relacionadas à sistematização da interpretação desses desfechos, a heterogeneidade de instrumentos de medida e a maior dificuldade na execução dos estudos, até o momento, parecem dificultar essa mudança. Além disso, a participação conjunta de pacientes, familiares, pesquisadores e clínicos na definição dos desfechos dos estudos ainda não é uma realidade.

Descritores:
Avaliação de resultados da assistência ao paciente; Estado terminal; Cuidados críticos; Prognóstico; Unidades de terapia

INTRODUCTION

Conceptually, the emergence of intensive care units (ICUs) was based on the premise of saving the lives of critically ill patients, i.e., reducing mortality. This goal was achieved in many clinical situations, such as sepsis(11 Stevenson EK, Rubenstein AR, Radin GT, Wiener RS, Walkey AJ. Two decades of mortality trends among patients with severe sepsis: a comparative meta-analysis. Crit Care Med. 2014;42(3):625-31.) and acute respiratory failure.(22 Zambon M, Vincent JL. Mortality rates for patients with acute lung injury/ARDS have decreased over time. Chest. 2008;133(5):1120-7.) This was due to progress in vital organ monitoring techniques,(33 Pool R, Gomez H, Kellum JA. Mechanisms of organ dysfunction in sepsis. Crit Care Clin. 2018;34(1):63-80.) to the organization and specialization of teams(44 Donovan AL, Aldrich JM, Gross AK, Barchas DM, Thornton KC, Schell-Chaple HM, Gropper MA, Lipshutz AKM; University of California, San Francisco Critical Care Innovations Group. Interprofessional care and teamwork in the ICU. Crit Care Med. 2018;46(6):980-90.

5 Halpern NA. Innovative designs for the smart ICU: Part 2: The ICU. Chest. 2014;145(3):646-58.
-66 Low XM, Horrigan D, Brewster DJ. The effects of team-training in intensive care medicine: a narrative review. J Crit Care. 2018;48:283-9.) and to improvements in symptomatic treatments of multiple organ dysfunction syndrome (MODS).(77 Armstrong BA, Betzold RD, May AK. Sepsis and Septic Shock Strategies. Surg Clin North Am. 2017;97(6):1339-79.)

Although the goal - mortality - remains valuable for intensivists, patient-centered outcomes have gained importance over the years. Among these outcomes are more effective pain control, evaluation of medium- and long-term results in those who survive a critical illness and greater attention to caregivers and family members (new class of patients).(88 Dinglas VD, Faraone LN, Needham DM. Understanding patient-important outcomes after critical illness: a synthesis of recent qualitative, empirical, and consensus-related studies. Curr Opin Crit Care. 2018;24(5):401-9.

9 Dinglas VD, Chessare CM, Davis WE, Parker A, Friedman LA, Colantuoni E, et al. Perspectives of survivors, families and researchers on key outcomes for research in acute respiratory failure. Thorax. 2018;73(1):7-12.
-1010 Gaudry S, Messika J, Ricard JD, Guillo S, Pasquet B, Dubief E, et al. Patient-important outcomes in randomized controlled trials in critically ill patients: a systematic review. Ann Intensive Care. 2017;7(1):28.)

Thus, the objective of this study is, through a narrative review, to describe the most important outcomes for critically ill patients, compare those with the outcomes most frequently studied in randomized clinical trials (RCTs) and describe possible barriers that prevent the evaluation of patient-centered outcomes in the intensive care setting.

METHODS

This is a nonsystematic review in which the bibliographic references of the retrieved studies were also searched to identify other relevant studies.

The MEDLINE® literature search was conducted in PubMed® on August 25, 2020, using search terms and synonyms for “patient-centered outcome” and “critical illness”. Only articles found in Portuguese, English and Spanish were reviewed, totaling 40,629 abstracts published in the last 10 years. Based on these abstracts, articles were selected for the development of this study. The articles were reviewed for their contribution to the current understanding of the outcomes evaluated in ICU patients, with priority for reviews, meta-analyses, systematic reviews and RCTs.

CURRENT FOCUS OF THE STUDY OF INTENSIVE CARE MEDICINE

The outcomes described in RCTs are distributed hierarchically.(1111 Agarwal A, Johnston BC, Vernooij RW, Carrasco-Labra A, Brignardello-Petersen R, Neumann I, et al. Authors seldom report the most patient-important outcomes and absolute effect measures in systematic review abstracts. J Clin Epidemiol. 2017;81:3-12.) The researchers characterize mortality (category 1) and morbidity (category 2; for example: need for hospitalization, recurrence of disease, and need for dialysis therapy, among others) as the most important outcomes. The presence of symptoms (e.g., pain, dyspnea, and fatigue, among others), quality of life and functional status are classified in category 3, surpassing in importance only the substitute outcomes of category 4 (e.g., blood pressure, oxygenation level, and levels of interleukins, among others). These authors believe that the study of mortality is a consensual opinion between physicians and patients and therefore indisputable.(99 Dinglas VD, Chessare CM, Davis WE, Parker A, Friedman LA, Colantuoni E, et al. Perspectives of survivors, families and researchers on key outcomes for research in acute respiratory failure. Thorax. 2018;73(1):7-12.,1212 Young K. Doctors' understanding of rheumatoid disease does not align with patients' experiences. BMJ. 2013;346:f2901.) In addition, other very important outcomes for physicians, such as the use of health resources or the duration of mechanical ventilation, seem to be much less important for patients when compared to the presence of pain or dyspnea.(99 Dinglas VD, Chessare CM, Davis WE, Parker A, Friedman LA, Colantuoni E, et al. Perspectives of survivors, families and researchers on key outcomes for research in acute respiratory failure. Thorax. 2018;73(1):7-12.) Thus, the answers that physicians seek when performing a clinical study are probably not the same as those that patients would like to obtain.(99 Dinglas VD, Chessare CM, Davis WE, Parker A, Friedman LA, Colantuoni E, et al. Perspectives of survivors, families and researchers on key outcomes for research in acute respiratory failure. Thorax. 2018;73(1):7-12.,1212 Young K. Doctors' understanding of rheumatoid disease does not align with patients' experiences. BMJ. 2013;346:f2901.

13 Richards T, Montori VM, Godlee F, Lapsley P, Paul D. Let the patient revolution begin. BMJ. 2013;346:f2614.
-1414 Pardo-Hernandez H, Alonso-Coello P. Patient-important outcomes in decision-making: a point of no return. J Clin Epidemiol. 2017;88:4-6.)

For critical illnesses, the outcomes evaluated in RCTs were previously categorized into different domains (Table 1).(1010 Gaudry S, Messika J, Ricard JD, Guillo S, Pasquet B, Dubief E, et al. Patient-important outcomes in randomized controlled trials in critically ill patients: a systematic review. Ann Intensive Care. 2017;7(1):28.,1515 Chrusch CA, Martin CM, Project TQ. Quality improvement in critical care: selection and development of quality indicators. Can Respir J. 2016;2016:2516765.) A systematic review by Gaudry et al.(1010 Gaudry S, Messika J, Ricard JD, Guillo S, Pasquet B, Dubief E, et al. Patient-important outcomes in randomized controlled trials in critically ill patients: a systematic review. Ann Intensive Care. 2017;7(1):28.) evaluated 112 RCTs involving critically ill patients who met the inclusion criteria defined by the authors. The topics most studied were mechanical ventilation (27%), sepsis (19%) and nutrition (17%). The authors identified that patient-centered outcomes were targeted in 65% of the RCTs evaluated. However, when the mortality outcome was excluded from the analysis, only 10% of studies evaluated other patient-centered outcomes, such as quality of life and physical or cognitive performance after discharge from the ICU. Figure 1 shows the prevalence of RCTs whose primary or secondary outcomes were patient-centered, as well as their distribution, based on the focus of the study.

Table 1
Categorization of outcomes in intensive care medicine
Table 2
Challenges for the greater use of long-term and patient-centered outcomes in intensive care

Figure 1
Prevalence of randomized clinical trials evaluating critically ill patients with primary or secondary patient-centered outcomes, as well as their distribution based on the focus of the study. The definitions “including mortality” and “excluding mortality” refer to the evaluation of all studies involving critically ill patients (MV + nutrition + sepsis). The definitions “MV”, “nutrition” and “sepsis” refer to studies of specific populations. The definition “excluding mortality” refers to the evaluation of other outcomes, in addition to mortality. MV - mechanical ventilation.

More recently, de Grooth et al.(1616 de Grooth HJ, Parienti JJ, Oudemans-van Straaten HM. Should we rely on trials with disease- rather than patient-oriented endpoints? Intensive Care Med. 2018;44(4):464-6.) demonstrated that intensive medicine journals with a high impact factor have increasingly published studies with primary outcomes focused on disease (e.g., MODS, days without mechanical ventilation, among others). This has occurred since 2016 and in studies with more than 200 - 500 patients. Outcomes focused on diseases are apparently valid but can be interpreted as ambiguous in relation to the real benefit for patients. Therapy can reduce organ failure without improving survival or quality of life, mistakenly suggesting that this new therapy actually benefits the patient.(1616 de Grooth HJ, Parienti JJ, Oudemans-van Straaten HM. Should we rely on trials with disease- rather than patient-oriented endpoints? Intensive Care Med. 2018;44(4):464-6.) Thus, the choice of disease-focused outcomes, in addition to potentially distant from the wishes of patients, can lead to illusory conclusions regarding the effectiveness of certain treatments. However, notably, when compared to RCTs that target patient-centered outcomes (e.g., mortality), the choice of disease-centered outcomes increase the authors’ chance of finding a positive outcome.(1717 Cavalcanti AB, Zampieri FG, Rosa RG, Azevedo LCP, Veiga VC, Avezum A, Damiani LP, Marcadenti A, Kawano-Dourado L, Lisboa T, Junqueira DL, de Barros E Silva PG, Tramujas L, Abreu-Silva EO, Laranjeira LN, Soares AT, Echenique LS, Pereira AJ, Freitas FG, Gebara OC, Dantas VC, Furtado RH, Milan EP, Golin NA, Cardoso FF, Maia IS, Hoffmann Filho CR, Kormann AP, Amazonas RB, Bocchi de Oliveira MF, Serpa-Neto A, Falavigna M, Lopes RD, Machado FR, Berwanger O; Coalition Covid-19 Brazil I Investigators. Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19. N Engl J Med. 2020;383(21):2041-52.,1818 Angus DC, Derde L, Al-Beidh F, Annane D, Arabi Y, Beane A, et al. Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. JAMA. 2020;324(13):1317-29.) That is, the sample size calculation is usually smaller because many of the surrogate outcomes are continuous or ordinal variables.

WHAT OUTCOMES ARE TRULY IMPORTANT FOR PATIENTS?

In clinical research, a relevant outcome for patients has been previously defined as a characteristic or variable that reflects how patients feel, function or survive.(1010 Gaudry S, Messika J, Ricard JD, Guillo S, Pasquet B, Dubief E, et al. Patient-important outcomes in randomized controlled trials in critically ill patients: a systematic review. Ann Intensive Care. 2017;7(1):28.,1919 Pino C, Boutron I, Ravaud P. Outcomes in registered, ongoing randomized controlled trials of patient education. PLoS One. 2012;7(8):e42934.) Clinical studies conducted in diabetic patients have shown that survival, quality of life, and functional, cognitive and neurological performance are the most important outcomes sought by this population.(2020 Gandhi GY, Murad MH, Fujiyoshi A, Mullan RJ, Flynn DN, Elamin MB, et al. Patient-important outcomes in registered diabetes trials. JAMA. 2008;299(21):2543-9.) However, when patients are placed in the center of care, the importance of doctors and their opinion decrease in the face of decisions, and they feel capable of making such decisions without the need for further discussion or sharing of expectations. Nevertheless, those most interested in outcomes are those who suffer them: the patients. Physicians and researchers should guide patients on technical issues and on the difficulties in measuring outcomes; however, they must include patients in the discussion and to choose the outcomes to be investigated in RCTs. Only with the participation of more patients in the construction of outcomes would this be possible, placing weight on the “preeminence of the values and preferences of the interested party”.(2121 Trujols J, Portella MJ, Iraurgi I, Campins MJ, Siñol N, de los Cobos JP. Patient-reported outcome measures: are they patient-generated, patient-centred or patient-valued? J Ment Health. 2013;22(6):555-62.) Thus, what outcomes should we measure in critically ill patients?

Long-term outcome measures

The study of ICU mortality will always be a marker of care quality.(1515 Chrusch CA, Martin CM, Project TQ. Quality improvement in critical care: selection and development of quality indicators. Can Respir J. 2016;2016:2516765.) However, the possible adverse consequences of an ICU stay are much better evaluated after discharge from this unit and, especially, after hospital discharge because critical illness is associated with high mortality(2222 Wunsch H, Guerra C, Barnato AE, Angus DC, Li G, Linde-Zwirble WT. Three-year outcomes for Medicare beneficiaries who survive intensive care. JAMA. 2010;303(9):849-56.

23 Biason BL, Teixeira C, Haas JS, Cabral CD, Friedman G. Effects of sepsis on morbidity and mortality in critically ill patients 2 years after intensive care unit discharge. Am J Crit Care. 2019;28(6):424-32.
-2424 Rosa RG, Falavigna M, Robinson CC, Sanchez EC, Kochhann R, Schneider D, Sganzerla D, Dietrich C, Barbosa MG, de Souza D, Rech GS, Dos Santos RD, da Silva AP, Santos MM, Dal Lago P, Sharshar T, Bozza FA, Teixeira C; Quality of Life After ICU Study Group Investigators and the BRICNet. Early and late mortality following discharge from the ICU: a multicenter prospective cohort study. Crit Care Med. 2020;48(1):64-72.) and a high prevalence of long-term adverse effects.(2525 Prescott HC, Angus DC. Enhancing recovery from sepsis: a review. JAMA. 2018;319(1):62-75.

26 Prince E, Gerstenblith TA, Davydow D, Bienvenu OJ. Psychiatric morbidity after critical illness. Crit Care Clin. 2018;34(4):599-608.

27 Oeyen SG, Vandijck DM, Benoit DD, Annemans L, Decruyenaere JM. Quality of life after intensive care: a systematic review of the literature. Crit Care Med. 2010;38(12):2386-400.
-2828 Wolters AE, Slooter AJC, van der Kooi AW, van Dijk D. Cognitive impairment after intensive care unit admission: a systematic review. Intensive Care Med. 2013;39(3):376-86.) Approximately 20% of American elderly patients who leave the hospital are readmitted within the first 30 days of discharge.(2929 Mæhlisen MH, Pasgaard AA, Mortensen RN, Vardinghus-Nielsen H, Torp-Pedersen C, Bøggild H. Perceived stress as a risk factor of unemployment: a register-based cohort study. BMC Public Health. 2018;18(1):728.

30 Wadhera RK, Joynt Maddox KE, Wasfy JH, Haneuse S, Shen C, Yeh RW. Association of the hospital readmissions reduction program with mortality among medicare beneficiaries hospitalized for heart failure, acute myocardial infarction, and pneumonia. JAMA. 2018;320(24):2542-52.
-3131 Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the medicare fee-for-service program. N Engl J Med. 2009;360(14):1418-28.) Survivors of sepsis have very high mortality in the first months (~40%)(3232 Prescott HC. Variation in postsepsis readmission patterns: a cohort study of veterans affairs beneficiaries. Ann Am Thorac Soc. 2017;14(2):230-7.) and years (~70%)(2323 Biason BL, Teixeira C, Haas JS, Cabral CD, Friedman G. Effects of sepsis on morbidity and mortality in critically ill patients 2 years after intensive care unit discharge. Am J Crit Care. 2019;28(6):424-32.,3333 Winters BD, Eberlein M, Leung J, Needham DM, Pronovost PJ, Sevransky JE. Long-term mortality and quality of life in sepsis: a systematic review. Crit Care Med. 2010;38(5):1276-83.) after discharge from the ICU. In addition, intensive care survivors experience profound changes in their lives due to the emergence of deficits in one or more domains(2525 Prescott HC, Angus DC. Enhancing recovery from sepsis: a review. JAMA. 2018;319(1):62-75.) of physical,(2323 Biason BL, Teixeira C, Haas JS, Cabral CD, Friedman G. Effects of sepsis on morbidity and mortality in critically ill patients 2 years after intensive care unit discharge. Am J Crit Care. 2019;28(6):424-32.,3434 Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304(16):1787-94.) psychological(3535 Nikayin S, Rabiee A, Hashem MD, Huang M, Bienvenu OJ, Turnbull AE, et al. Anxiety symptoms in survivors of critical illness: a systematic review and meta-analysis. Gen Hosp Psychiatry. 2016;43:23-9.

36 Rabiee A, Nikayin S, Hashem MD, Huang M, Dinglas VD, Bienvenu OJ, et al. Depressive symptoms after critical illness: a systematic review and meta-analysis. Crit Care Med. 2016;44(9):1744-53.
-3737 Righy C, Rosa RG, da Silva RT, Kochhann R, Migliavaca CB, Robinson CC, et al. Prevalence of post-traumatic stress disorder symptoms in adult critical care survivors: a systematic review and meta-analysis. Crit Care. 2019;23(1):213.) or cognitive functions.(3838 Girard TD. Sedation, delirium, and cognitive function after critical illness. Crit Care Clin. 2018;34(4):585-98.)

Thus, an important decision would be to migrate the evaluation of patients’ outcomes from inside the hospital to outside. This, however, is not yet a reality. Gaudry et al.(1010 Gaudry S, Messika J, Ricard JD, Guillo S, Pasquet B, Dubief E, et al. Patient-important outcomes in randomized controlled trials in critically ill patients: a systematic review. Ann Intensive Care. 2017;7(1):28.) showed that of the 73 RCTs included in a systematic review evaluating outcomes in critically ill patients, only 17.8% followed the patients for more than 30 days after ICU admission. In addition, the choice of long-term outcomes could hinder the performance and evaluation of clinical studies with critically ill patient populations (Table 2). The higher risk of loss to follow-up may increase selection bias. The high heterogeneity of the instruments used to evaluate patient-centered outcomes in the context of ICU discharge may hinder the adequate summarization and reproducibility of the evidence.(3939 Turnbull AE, Rabiee A, Davis WE, Nasser MF, Venna VR, Lolitha R, et al. Outcome measurement in ICU survivorship research from 1970 to 2013: a scoping review of 425 publications. Crit Care Med. 2016;44(7):1267-77.) For example, in 425 publications examining ICU survivors after hospital discharge, 250 different measurement instruments were identified. Quality of life was the most frequently reported outcome (in 65% of the articles). Physical activity limitations, an outcome that is also highly relevant for patients, appeared in only 6% of the articles. Although this high heterogeneity reflects the growing nature of this research field, it negatively reflects the lack of standardization of measurement instruments,(88 Dinglas VD, Faraone LN, Needham DM. Understanding patient-important outcomes after critical illness: a synthesis of recent qualitative, empirical, and consensus-related studies. Curr Opin Crit Care. 2018;24(5):401-9.) which limits comparisons among studies and hinders the performance of meta-analyses.(4040 Williamson PR, Altman DG, Blazeby JM, Clarke M, Devane D, Gargon E, et al. Developing core outcome sets for clinical trials: issues to consider. Trials. 2012;13:132.) Finally, many interview instruments have not yet been validated for their application via telephone, a fundamental requirement for the long-term follow-up of patients.

Evaluation of mortality associated with quality of life

In the hierarchical distribution of outcomes, mortality always has a prominent role.(1111 Agarwal A, Johnston BC, Vernooij RW, Carrasco-Labra A, Brignardello-Petersen R, Neumann I, et al. Authors seldom report the most patient-important outcomes and absolute effect measures in systematic review abstracts. J Clin Epidemiol. 2017;81:3-12.) However, is survival as important for patients as it is for doctors? In studies evaluating the post-ICU life of patients with acute respiratory distress syndrome (ARDS), survival was the outcome best evaluated by researchers and physicians; yet, it was the second least important outcome ranked by patients.(99 Dinglas VD, Chessare CM, Davis WE, Parker A, Friedman LA, Colantuoni E, et al. Perspectives of survivors, families and researchers on key outcomes for research in acute respiratory failure. Thorax. 2018;73(1):7-12.) This inconsistency could be explained by the study sample, composed only of ICU survivors (obviously not evaluating the deceased); by the propensity of researchers to increase the importance of survival due to their awareness of the importance of accounting for death when evaluating functional outcomes after hospital discharge; and by the common practice of evaluating mortality as the primary outcome in intensive care studies.(1010 Gaudry S, Messika J, Ricard JD, Guillo S, Pasquet B, Dubief E, et al. Patient-important outcomes in randomized controlled trials in critically ill patients: a systematic review. Ann Intensive Care. 2017;7(1):28.)

Unfortunately, surviving critical illness is associated with a wide variety of long-term physical and psychological sequelae that may affect functional status and quality of life.(2525 Prescott HC, Angus DC. Enhancing recovery from sepsis: a review. JAMA. 2018;319(1):62-75.

26 Prince E, Gerstenblith TA, Davydow D, Bienvenu OJ. Psychiatric morbidity after critical illness. Crit Care Clin. 2018;34(4):599-608.

27 Oeyen SG, Vandijck DM, Benoit DD, Annemans L, Decruyenaere JM. Quality of life after intensive care: a systematic review of the literature. Crit Care Med. 2010;38(12):2386-400.
-2828 Wolters AE, Slooter AJC, van der Kooi AW, van Dijk D. Cognitive impairment after intensive care unit admission: a systematic review. Intensive Care Med. 2013;39(3):376-86.) Thus, the value of quality of life as a central outcome for ICU survivors is increasing.(2727 Oeyen SG, Vandijck DM, Benoit DD, Annemans L, Decruyenaere JM. Quality of life after intensive care: a systematic review of the literature. Crit Care Med. 2010;38(12):2386-400.,4141 Dowdy DW, Eid MP, Sedrakyan A, Mendez-Tellez PA, Pronovost PJ, Herridge MS, et al. Quality of life in adult survivors of critical illness: a systematic review of the literature. Intensive Care Med. 2005;31(5):611-20.) This is an outcome reported by patients themselves, without external interference from researchers or family members. It values the patient’s perspective and allows the evaluation of the real impact of a disease and the consequences of its treatment from a multidimensional aspect (i.e., extrapolating the simple definition of morbidity or mortality). Such multidimensionality makes it possible to evaluate an individual’s perception in relation to different domains of his or her life, such as physical aspects, day-to-day functioning, social performance and emotional aspects.(2727 Oeyen SG, Vandijck DM, Benoit DD, Annemans L, Decruyenaere JM. Quality of life after intensive care: a systematic review of the literature. Crit Care Med. 2010;38(12):2386-400.) Thus, a good quality of life could increase patient satisfaction more so than determinations of reduced motor capacity or the ability to perform basic or instrumental activities of daily living.

In this view, alone, the survival of a patient who was critically ill does not allow assessing whether he or she recovered his or her happiness, activities, and ability to interact with the environment. Surviving, therefore, does not necessarily mean having quality of life. The authors suggest that both outcomes should always be evaluated together.

Combined outcomes of patients, family and/or caregivers

In clinical research environments and long-term follow-up, family members or caregivers are usually informants of the evolution of ICU survivors. However, is patient information reliable? It seems so. In a study conducted with ARDS survivors, researchers and family members were also interviewed.(99 Dinglas VD, Chessare CM, Davis WE, Parker A, Friedman LA, Colantuoni E, et al. Perspectives of survivors, families and researchers on key outcomes for research in acute respiratory failure. Thorax. 2018;73(1):7-12.) Of the 19 important outcomes selected by the researchers, approximately 80% also showed agreement between patients and their families. The best ranked outcomes were physical function, pulmonary symptoms, cognitive symptoms, mental health symptoms, pain, fatigue, and the ability to return to work or previous activities. Social roles, activities and relationships, survival and sexual symptoms had the lowest levels of agreement. These data highlight that family members serve as substitute informants of patient-centered outcomes (in case of inability to evaluate the patient), aiming to minimize the loss of data related to possible disabilities or the unavailability of patients to answer questionnaires. Notably, family members of critically ill patients usually get sick along with them. Family members experience a high psychological burden in the first year after patient discharge(4242 Cameron JI, Chu LM, Matte A, Tomlinson G, Chan L, Thomas C, Friedrich JO, Mehta S, Lamontagne F, Levasseur M, Ferguson ND, Adhikari NK, Rudkowski JC, Meggison H, Skrobik Y, Flannery J, Bayley M, Batt J, dos Santos C, Abbey SE, Tan A, Lo V, Mathur S, Parotto M, Morris D, Flockhart L, Fan E, Lee CM, Wilcox ME, Ayas N, Choong K, Fowler R, Scales DC, Sinuff T, Cuthbertson BH, Rose L, Robles P, Burns S, Cypel M, Singer L, Chaparro C, Chow CW, Keshavjee S, Brochard L, Hébert P, Slutsky AS, Marshall JC, Cook D, Herridge MS; RECOVER Program Investigators (Phase 1: towards RECOVER); Canadian Critical Care Trials Group. One-year outcomes in caregivers of critically ill patients. N Engl J Med. 2016;374(19):1831-41.,4343 van Beusekom I, Bakhshi-Raiez F, de Keizer NF, Dongelmans DA, van der Schaaf M. Reported burden on informal caregivers of ICU survivors: a literature review. Crit Care. 2016;20:16.) as they are suddenly and unpreparedly forced to assume decision-making roles in relation to the conduct and treatment of their loved ones. Thus, considering family members and caregivers as a population that should have their outcomes studied seems logical, in addition to the fact that keeping them in clinical follow-up could bring them benefits.(4444 Ullman AJ, Aitken LM, Rattray J, Kenardy J, Le Brocque R, MacGillivray S, et al. Intensive care diaries to promote recovery for patients and families after critical illness: a Cochrane Systematic Review. Int J Nurs Stud. 2015;52(7):1243-53.)

BARRIERS TO IMPLEMENTING CHANGE

Change is difficult to accept in any field of science, be it exact or social.(4545 Handley MA, Gorukanti A, Cattamanchi A. Strategies for implementing implementation science: a methodological overview. Emerg Med J. 2016;33(9):660-4.) The trade of a “paternalistic model” of medical decision-making to a “model of sharing” decisions with patients (in which the “patient is at the center” of medical decision-making) has been changing the scale of importance of the outcomes studied. It seems that now there is less interest in what is a “clinically relevant” effect and more emphasis on what is “important for the patient”.(1616 de Grooth HJ, Parienti JJ, Oudemans-van Straaten HM. Should we rely on trials with disease- rather than patient-oriented endpoints? Intensive Care Med. 2018;44(4):464-6.,4646 Brown SM, Rozenblum R, Aboumatar H, Fagan MB, Milic M, Lee BS, et al. Defining patient and family engagement in the intensive care unit. Am J Respir Crit Care Med. 2015;191(3):358-60.,4747 Burns KE, Misak C, Herridge M, Meade MO, Oczkowski S; Patient and Family Partnership Committee of the Canadian Critical Care Trials Group. Patient and family engagement in the ICU. Untapped opportunities and underrecognized challenges. Am J Respir Crit Care Med. 2018;198(3):310-9.)

Some difficulties are expected as this slow change occurs in scientific studies of critically ill patients. First, to date, there is no taxonomy of the outcomes studied in critically ill patients or a defined grouping of the set of outcomes.(1010 Gaudry S, Messika J, Ricard JD, Guillo S, Pasquet B, Dubief E, et al. Patient-important outcomes in randomized controlled trials in critically ill patients: a systematic review. Ann Intensive Care. 2017;7(1):28.,4040 Williamson PR, Altman DG, Blazeby JM, Clarke M, Devane D, Gargon E, et al. Developing core outcome sets for clinical trials: issues to consider. Trials. 2012;13:132.,4848 Young B, Bagley H. Including patients in core outcome set development: issues to consider based on three workshops with around 100 international delegates. Res Involv Engagem. 2016;2:25.,4949 Prinsen CA, Vohra S, Rose MR, King-Jones S, Ishaque S, Bhaloo Z, et al. Core Outcome Measures in Effectiveness Trials (COMET) initiative: protocol for an international Delphi study to achieve consensus on how to select outcome measurement instruments for outcomes included in a "core outcome set." Trials. 2014;15:247.) However, some experiments are already being performed in some medical specialties, such as rheumatology(5050 Kirkham JJ, Boers M, Tugwell P, Clarke M, Williamson PR. Outcome measures in rheumatoid arthritis randomised trials over the last 50 years. Trials. 2013;14:324.,5151 Petkovic J, Barton JL, Flurey C, Goel N, Bartels CM, Barnabe C, et al. Health equity considerations for developing and reporting patient-reported outcomes in clinical trials: a report from the OMERACT Equity Special Interest Group. J Rheumatol. 2017;44(11):1727-33.) and endocrinology,(2020 Gandhi GY, Murad MH, Fujiyoshi A, Mullan RJ, Flynn DN, Elamin MB, et al. Patient-important outcomes in registered diabetes trials. JAMA. 2008;299(21):2543-9.) and in patient education studies.(1919 Pino C, Boutron I, Ravaud P. Outcomes in registered, ongoing randomized controlled trials of patient education. PLoS One. 2012;7(8):e42934.) Additionally, in the area of intensive care, initiatives in the areas of ventilatory support(5252 Blackwood B, Ringrow S, Clarke M, Marshall J, Rose L, Williamson P, et al. Core Outcomes in Ventilation Trials (COVenT): protocol for a core outcome set using a Delphi survey with a nested randomised trial and observational cohort study. Trials. 2015;16:368.) and acute respiratory failure(5353 Needham DM, Sepulveda KA, Dinglas VD, Chessare CM, Friedman LA, Bingham CO 3rd, 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(9):1122-30.

54 Turnbull AE, Sepulveda KA, Dinglas VD, Chessare CM, Bingham CO 3rd, Needham DM. Core Domains for Clinical Research in Acute Respiratory Failure Survivors: An International Modified Delphi Consensus Study. Crit Care Med. 2017;45(6):1001-10.
-5555 Hodgson CL, Burrell AJ, Engeler DM, Pellegrino VA, Brodie D, Fan E; International ECMO Network. Core Outcome Measures for Research in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation for Acute Respiratory or Cardiac Failure: An International, Multidisciplinary, Modified Delphi Consensus Study. Crit Care Med. 2019;47(11):1557-63.) have emerged.

Second, the discovery of how different the expectations of patients and physicians are regarding the outcomes proposed in studies is relatively recent,(99 Dinglas VD, Chessare CM, Davis WE, Parker A, Friedman LA, Colantuoni E, et al. Perspectives of survivors, families and researchers on key outcomes for research in acute respiratory failure. Thorax. 2018;73(1):7-12.,1212 Young K. Doctors' understanding of rheumatoid disease does not align with patients' experiences. BMJ. 2013;346:f2901.,1313 Richards T, Montori VM, Godlee F, Lapsley P, Paul D. Let the patient revolution begin. BMJ. 2013;346:f2614.,5656 Miika M. Seeking Clarity on FDA Medical Apps Oversight. JAMA. 2014;311(18):1847.,5757 Frank L, Forsythe L, Ellis L, Schrandt S, Sheridan S, Gerson J, et al. Conceptual and practical foundations of patient engagement in research at the patient-centered outcomes research institute. Qual Life Res. 2015;24(5):1033-41.) that is, still too early to be common knowledge among the entire medical community.

Third, methods to involve patients in determining patient-centered outcomes are still under development and include conducting qualitative research.(5858 Eakin MN, Patel Y, Mendez-Tellez P, Dinglas VD, Needham DM, Turnbull AE. Patients´outcomes after acute respiratory failure: a qualitative study with the PROMIS Framework. Am J Crit Care. 2017;26(6):456-65.) as well as the need for patient participation in health-related meetings or conferences.(88 Dinglas VD, Faraone LN, Needham DM. Understanding patient-important outcomes after critical illness: a synthesis of recent qualitative, empirical, and consensus-related studies. Curr Opin Crit Care. 2018;24(5):401-9.,4040 Williamson PR, Altman DG, Blazeby JM, Clarke M, Devane D, Gargon E, et al. Developing core outcome sets for clinical trials: issues to consider. Trials. 2012;13:132.,5757 Frank L, Forsythe L, Ellis L, Schrandt S, Sheridan S, Gerson J, et al. Conceptual and practical foundations of patient engagement in research at the patient-centered outcomes research institute. Qual Life Res. 2015;24(5):1033-41.) To date, few medical conferences allow active participation of patients in discussion sessions.

Fourth, opting for primary outcomes focused on disease (e.g., oxygenation index, organ failure score, shock reversal time, and ventilation-free days, among others) usually requires a smaller sample size and may be a more sensitive indicator of the effects of a given treatment, when compared to truly important outcomes (such as survival or quality of life).(1616 de Grooth HJ, Parienti JJ, Oudemans-van Straaten HM. Should we rely on trials with disease- rather than patient-oriented endpoints? Intensive Care Med. 2018;44(4):464-6.)

Finally, the choice of a composite outcome (a disease-centered outcome associated with a patient-centered outcome) to facilitate the execution of a study could be difficult to interpret because the treatment offered often has different effects on each individual components of the outcome.(1616 de Grooth HJ, Parienti JJ, Oudemans-van Straaten HM. Should we rely on trials with disease- rather than patient-oriented endpoints? Intensive Care Med. 2018;44(4):464-6.) This fact could greatly complicate the interpretation of this “new” composite outcome proposed for studies.

FINAL CONSIDERATIONS

Disease-centered primary outcomes have become more prevalent in intensive care studies. The choice of patient-centered outcomes would correct the wrong course of current medical research. However, numerous financial, organizational, and individual barriers prevent this “correct” transition to occur as quickly as it should. The choice of an outcome in a scientific study should be built in collaboration, in which the patient, family, researcher and clinician perspectives are evaluated, discussed, and synthesized to obtain a cohesive and representative understanding of the results that would be important for the patients, in addition of being easy to perform and interpret by physicians, relatives and researchers.

REFERÊNCIAS

  • 1
    Stevenson EK, Rubenstein AR, Radin GT, Wiener RS, Walkey AJ. Two decades of mortality trends among patients with severe sepsis: a comparative meta-analysis. Crit Care Med. 2014;42(3):625-31.
  • 2
    Zambon M, Vincent JL. Mortality rates for patients with acute lung injury/ARDS have decreased over time. Chest. 2008;133(5):1120-7.
  • 3
    Pool R, Gomez H, Kellum JA. Mechanisms of organ dysfunction in sepsis. Crit Care Clin. 2018;34(1):63-80.
  • 4
    Donovan AL, Aldrich JM, Gross AK, Barchas DM, Thornton KC, Schell-Chaple HM, Gropper MA, Lipshutz AKM; University of California, San Francisco Critical Care Innovations Group. Interprofessional care and teamwork in the ICU. Crit Care Med. 2018;46(6):980-90.
  • 5
    Halpern NA. Innovative designs for the smart ICU: Part 2: The ICU. Chest. 2014;145(3):646-58.
  • 6
    Low XM, Horrigan D, Brewster DJ. The effects of team-training in intensive care medicine: a narrative review. J Crit Care. 2018;48:283-9.
  • 7
    Armstrong BA, Betzold RD, May AK. Sepsis and Septic Shock Strategies. Surg Clin North Am. 2017;97(6):1339-79.
  • 8
    Dinglas VD, Faraone LN, Needham DM. Understanding patient-important outcomes after critical illness: a synthesis of recent qualitative, empirical, and consensus-related studies. Curr Opin Crit Care. 2018;24(5):401-9.
  • 9
    Dinglas VD, Chessare CM, Davis WE, Parker A, Friedman LA, Colantuoni E, et al. Perspectives of survivors, families and researchers on key outcomes for research in acute respiratory failure. Thorax. 2018;73(1):7-12.
  • 10
    Gaudry S, Messika J, Ricard JD, Guillo S, Pasquet B, Dubief E, et al. Patient-important outcomes in randomized controlled trials in critically ill patients: a systematic review. Ann Intensive Care. 2017;7(1):28.
  • 11
    Agarwal A, Johnston BC, Vernooij RW, Carrasco-Labra A, Brignardello-Petersen R, Neumann I, et al. Authors seldom report the most patient-important outcomes and absolute effect measures in systematic review abstracts. J Clin Epidemiol. 2017;81:3-12.
  • 12
    Young K. Doctors' understanding of rheumatoid disease does not align with patients' experiences. BMJ. 2013;346:f2901.
  • 13
    Richards T, Montori VM, Godlee F, Lapsley P, Paul D. Let the patient revolution begin. BMJ. 2013;346:f2614.
  • 14
    Pardo-Hernandez H, Alonso-Coello P. Patient-important outcomes in decision-making: a point of no return. J Clin Epidemiol. 2017;88:4-6.
  • 15
    Chrusch CA, Martin CM, Project TQ. Quality improvement in critical care: selection and development of quality indicators. Can Respir J. 2016;2016:2516765.
  • 16
    de Grooth HJ, Parienti JJ, Oudemans-van Straaten HM. Should we rely on trials with disease- rather than patient-oriented endpoints? Intensive Care Med. 2018;44(4):464-6.
  • 17
    Cavalcanti AB, Zampieri FG, Rosa RG, Azevedo LCP, Veiga VC, Avezum A, Damiani LP, Marcadenti A, Kawano-Dourado L, Lisboa T, Junqueira DL, de Barros E Silva PG, Tramujas L, Abreu-Silva EO, Laranjeira LN, Soares AT, Echenique LS, Pereira AJ, Freitas FG, Gebara OC, Dantas VC, Furtado RH, Milan EP, Golin NA, Cardoso FF, Maia IS, Hoffmann Filho CR, Kormann AP, Amazonas RB, Bocchi de Oliveira MF, Serpa-Neto A, Falavigna M, Lopes RD, Machado FR, Berwanger O; Coalition Covid-19 Brazil I Investigators. Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19. N Engl J Med. 2020;383(21):2041-52.
  • 18
    Angus DC, Derde L, Al-Beidh F, Annane D, Arabi Y, Beane A, et al. Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. JAMA. 2020;324(13):1317-29.
  • 19
    Pino C, Boutron I, Ravaud P. Outcomes in registered, ongoing randomized controlled trials of patient education. PLoS One. 2012;7(8):e42934.
  • 20
    Gandhi GY, Murad MH, Fujiyoshi A, Mullan RJ, Flynn DN, Elamin MB, et al. Patient-important outcomes in registered diabetes trials. JAMA. 2008;299(21):2543-9.
  • 21
    Trujols J, Portella MJ, Iraurgi I, Campins MJ, Siñol N, de los Cobos JP. Patient-reported outcome measures: are they patient-generated, patient-centred or patient-valued? J Ment Health. 2013;22(6):555-62.
  • 22
    Wunsch H, Guerra C, Barnato AE, Angus DC, Li G, Linde-Zwirble WT. Three-year outcomes for Medicare beneficiaries who survive intensive care. JAMA. 2010;303(9):849-56.
  • 23
    Biason BL, Teixeira C, Haas JS, Cabral CD, Friedman G. Effects of sepsis on morbidity and mortality in critically ill patients 2 years after intensive care unit discharge. Am J Crit Care. 2019;28(6):424-32.
  • 24
    Rosa RG, Falavigna M, Robinson CC, Sanchez EC, Kochhann R, Schneider D, Sganzerla D, Dietrich C, Barbosa MG, de Souza D, Rech GS, Dos Santos RD, da Silva AP, Santos MM, Dal Lago P, Sharshar T, Bozza FA, Teixeira C; Quality of Life After ICU Study Group Investigators and the BRICNet. Early and late mortality following discharge from the ICU: a multicenter prospective cohort study. Crit Care Med. 2020;48(1):64-72.
  • 25
    Prescott HC, Angus DC. Enhancing recovery from sepsis: a review. JAMA. 2018;319(1):62-75.
  • 26
    Prince E, Gerstenblith TA, Davydow D, Bienvenu OJ. Psychiatric morbidity after critical illness. Crit Care Clin. 2018;34(4):599-608.
  • 27
    Oeyen SG, Vandijck DM, Benoit DD, Annemans L, Decruyenaere JM. Quality of life after intensive care: a systematic review of the literature. Crit Care Med. 2010;38(12):2386-400.
  • 28
    Wolters AE, Slooter AJC, van der Kooi AW, van Dijk D. Cognitive impairment after intensive care unit admission: a systematic review. Intensive Care Med. 2013;39(3):376-86.
  • 29
    Mæhlisen MH, Pasgaard AA, Mortensen RN, Vardinghus-Nielsen H, Torp-Pedersen C, Bøggild H. Perceived stress as a risk factor of unemployment: a register-based cohort study. BMC Public Health. 2018;18(1):728.
  • 30
    Wadhera RK, Joynt Maddox KE, Wasfy JH, Haneuse S, Shen C, Yeh RW. Association of the hospital readmissions reduction program with mortality among medicare beneficiaries hospitalized for heart failure, acute myocardial infarction, and pneumonia. JAMA. 2018;320(24):2542-52.
  • 31
    Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the medicare fee-for-service program. N Engl J Med. 2009;360(14):1418-28.
  • 32
    Prescott HC. Variation in postsepsis readmission patterns: a cohort study of veterans affairs beneficiaries. Ann Am Thorac Soc. 2017;14(2):230-7.
  • 33
    Winters BD, Eberlein M, Leung J, Needham DM, Pronovost PJ, Sevransky JE. Long-term mortality and quality of life in sepsis: a systematic review. Crit Care Med. 2010;38(5):1276-83.
  • 34
    Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304(16):1787-94.
  • 35
    Nikayin S, Rabiee A, Hashem MD, Huang M, Bienvenu OJ, Turnbull AE, et al. Anxiety symptoms in survivors of critical illness: a systematic review and meta-analysis. Gen Hosp Psychiatry. 2016;43:23-9.
  • 36
    Rabiee A, Nikayin S, Hashem MD, Huang M, Dinglas VD, Bienvenu OJ, et al. Depressive symptoms after critical illness: a systematic review and meta-analysis. Crit Care Med. 2016;44(9):1744-53.
  • 37
    Righy C, Rosa RG, da Silva RT, Kochhann R, Migliavaca CB, Robinson CC, et al. Prevalence of post-traumatic stress disorder symptoms in adult critical care survivors: a systematic review and meta-analysis. Crit Care. 2019;23(1):213.
  • 38
    Girard TD. Sedation, delirium, and cognitive function after critical illness. Crit Care Clin. 2018;34(4):585-98.
  • 39
    Turnbull AE, Rabiee A, Davis WE, Nasser MF, Venna VR, Lolitha R, et al. Outcome measurement in ICU survivorship research from 1970 to 2013: a scoping review of 425 publications. Crit Care Med. 2016;44(7):1267-77.
  • 40
    Williamson PR, Altman DG, Blazeby JM, Clarke M, Devane D, Gargon E, et al. Developing core outcome sets for clinical trials: issues to consider. Trials. 2012;13:132.
  • 41
    Dowdy DW, Eid MP, Sedrakyan A, Mendez-Tellez PA, Pronovost PJ, Herridge MS, et al. Quality of life in adult survivors of critical illness: a systematic review of the literature. Intensive Care Med. 2005;31(5):611-20.
  • 42
    Cameron JI, Chu LM, Matte A, Tomlinson G, Chan L, Thomas C, Friedrich JO, Mehta S, Lamontagne F, Levasseur M, Ferguson ND, Adhikari NK, Rudkowski JC, Meggison H, Skrobik Y, Flannery J, Bayley M, Batt J, dos Santos C, Abbey SE, Tan A, Lo V, Mathur S, Parotto M, Morris D, Flockhart L, Fan E, Lee CM, Wilcox ME, Ayas N, Choong K, Fowler R, Scales DC, Sinuff T, Cuthbertson BH, Rose L, Robles P, Burns S, Cypel M, Singer L, Chaparro C, Chow CW, Keshavjee S, Brochard L, Hébert P, Slutsky AS, Marshall JC, Cook D, Herridge MS; RECOVER Program Investigators (Phase 1: towards RECOVER); Canadian Critical Care Trials Group. One-year outcomes in caregivers of critically ill patients. N Engl J Med. 2016;374(19):1831-41.
  • 43
    van Beusekom I, Bakhshi-Raiez F, de Keizer NF, Dongelmans DA, van der Schaaf M. Reported burden on informal caregivers of ICU survivors: a literature review. Crit Care. 2016;20:16.
  • 44
    Ullman AJ, Aitken LM, Rattray J, Kenardy J, Le Brocque R, MacGillivray S, et al. Intensive care diaries to promote recovery for patients and families after critical illness: a Cochrane Systematic Review. Int J Nurs Stud. 2015;52(7):1243-53.
  • 45
    Handley MA, Gorukanti A, Cattamanchi A. Strategies for implementing implementation science: a methodological overview. Emerg Med J. 2016;33(9):660-4.
  • 46
    Brown SM, Rozenblum R, Aboumatar H, Fagan MB, Milic M, Lee BS, et al. Defining patient and family engagement in the intensive care unit. Am J Respir Crit Care Med. 2015;191(3):358-60.
  • 47
    Burns KE, Misak C, Herridge M, Meade MO, Oczkowski S; Patient and Family Partnership Committee of the Canadian Critical Care Trials Group. Patient and family engagement in the ICU. Untapped opportunities and underrecognized challenges. Am J Respir Crit Care Med. 2018;198(3):310-9.
  • 48
    Young B, Bagley H. Including patients in core outcome set development: issues to consider based on three workshops with around 100 international delegates. Res Involv Engagem. 2016;2:25.
  • 49
    Prinsen CA, Vohra S, Rose MR, King-Jones S, Ishaque S, Bhaloo Z, et al. Core Outcome Measures in Effectiveness Trials (COMET) initiative: protocol for an international Delphi study to achieve consensus on how to select outcome measurement instruments for outcomes included in a "core outcome set." Trials. 2014;15:247.
  • 50
    Kirkham JJ, Boers M, Tugwell P, Clarke M, Williamson PR. Outcome measures in rheumatoid arthritis randomised trials over the last 50 years. Trials. 2013;14:324.
  • 51
    Petkovic J, Barton JL, Flurey C, Goel N, Bartels CM, Barnabe C, et al. Health equity considerations for developing and reporting patient-reported outcomes in clinical trials: a report from the OMERACT Equity Special Interest Group. J Rheumatol. 2017;44(11):1727-33.
  • 52
    Blackwood B, Ringrow S, Clarke M, Marshall J, Rose L, Williamson P, et al. Core Outcomes in Ventilation Trials (COVenT): protocol for a core outcome set using a Delphi survey with a nested randomised trial and observational cohort study. Trials. 2015;16:368.
  • 53
    Needham DM, Sepulveda KA, Dinglas VD, Chessare CM, Friedman LA, Bingham CO 3rd, 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(9):1122-30.
  • 54
    Turnbull AE, Sepulveda KA, Dinglas VD, Chessare CM, Bingham CO 3rd, Needham DM. Core Domains for Clinical Research in Acute Respiratory Failure Survivors: An International Modified Delphi Consensus Study. Crit Care Med. 2017;45(6):1001-10.
  • 55
    Hodgson CL, Burrell AJ, Engeler DM, Pellegrino VA, Brodie D, Fan E; International ECMO Network. Core Outcome Measures for Research in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation for Acute Respiratory or Cardiac Failure: An International, Multidisciplinary, Modified Delphi Consensus Study. Crit Care Med. 2019;47(11):1557-63.
  • 56
    Miika M. Seeking Clarity on FDA Medical Apps Oversight. JAMA. 2014;311(18):1847.
  • 57
    Frank L, Forsythe L, Ellis L, Schrandt S, Sheridan S, Gerson J, et al. Conceptual and practical foundations of patient engagement in research at the patient-centered outcomes research institute. Qual Life Res. 2015;24(5):1033-41.
  • 58
    Eakin MN, Patel Y, Mendez-Tellez P, Dinglas VD, Needham DM, Turnbull AE. Patients´outcomes after acute respiratory failure: a qualitative study with the PROMIS Framework. Am J Crit Care. 2017;26(6):456-65.

Publication Dates

  • Publication in this collection
    05 July 2021
  • Date of issue
    Apr-Jun 2021

History

  • Received
    12 May 2020
  • Accepted
    04 Oct 2020
Associação de Medicina Intensiva Brasileira - AMIB Rua Arminda, 93 - Vila Olímpia, CEP 04545-100 - São Paulo - SP - Brasil, Tel.: (11) 5089-2642 - São Paulo - SP - Brazil
E-mail: rbti.artigos@amib.com.br