A survey of Delphi panelists after core outcome set development revealed positive feedback and methods to facilitate panel member participation.

OBJECTIVES: The objective of this study was to elicit feedback on consensus methodology used for core outcome set (COS) development. STUDY DESIGN AND SETTING: An online survey of international Delphi panelists participating in a recent COS for clinical research studies evaluating acute respiratory failure (ARF) survivors was conducted. Panelists represented 14 countries (56% outside the United States). RESULTS: Seventy (92%) panelists completed the survey, including 32 researchers, 19 professional association representatives, 4 research funding representatives, and 15 ARF survivors/caregiver members. Among respondents, 91% reported that the time required to participate was appropriate and 96% were not bothered by reminders for timely response. Attributes of measurement instruments and voting results from previous rounds were evaluated differently across stakeholder groups. When measurement properties were explained in the stem of the survey question, 59 (84%) panelists (including 73% of survivors/families) correctly interpreted information about an instrument's reliability. Without a reminder in the stem, only 20 (29%) panelists (including 38% of researchers) correctly identified properties of a COS. CONCLUSION: This international Delphi panel, including >20% patients/caregivers, favorably reported on feasibility of the methodology. Providing all panelists pertinent information/reminders about the project's objective at each voting round is important to informed decision making across all stakeholder groups.

Factors associated with missed assessments in a 2-year longitudinal study of acute respiratory distress syndrome survivors.

BACKGROUND: To evaluate participant-related variables associated with missing assessment(s) at follow-up visits during a longitudinal research study. METHODS: This is a prospective, longitudinal, multi-site study of 196 acute respiratory distress syndrome (ARDS) survivors. More than 30 relevant sociodemographic, physical status, and mental health variables (representing participant characteristics prior to ARDS, at hospital discharge, and at the immediately preceding follow-up visit) were evaluated for association with missed assessments at 3, 6, 12, and 24-month follow-up visits (89-95% retention rates), using binomial logistic regression. RESULTS: Most participants were male (56%), white (58%), and ≤ high school education (64%). Sociodemographic characteristics were not associated with missed assessments at the initial 3-month visit or subsequent visits. The number of dependencies in Activities of Daily Living (ADLs) at hospital discharge was associated with higher odds of missed assessments at the initial visit (OR: 1.26, 95% CI: 1.12, 1.43). At subsequent 6-, 12-, and 24 months visits, post-hospital discharge physical and psychological status were not associated with subsequent missed assessments. Instead, the following were associated with lower odds of missed assessments: indicators of poorer health prior to hospital admission (inability to walk 5 min (OR: 0.46; 0.23, 0.91), unemployment due to health (OR: 0.47; 0.23, 0.96), and alcohol abuse (OR: 0.53; 0.28, 0.97)) and having the preceding visit at the research clinic rather than at home/facility, or by phone/mail (OR: 0.54; 0.31, 0.96). Inversely, variables associated with higher odds of missed assessments at subsequent visits include: functional dependency prior to hospital admission (i.e. dependency with > = 2 Instrumental Activities of Daily Living (IADLs) (OR: 1.96; 1.08, 3.52), and missing assessments at preceding visit (OR: 2.26; 1.35, 3.79). CONCLUSIONS: During the recovery process after hospital discharge, dependencies in physical functioning (e.g. ADLs, IADLs) prior to hospitalization and at hospital discharge were associated with higher odds of missed assessments. Conversely, other indicators of poorer health at baseline were associated with lower odds of missed assessments after the initial post-discharge visit. To reduce missing assessments, longitudinal clinical research studies may benefit from focusing additional resources on participants with dependencies in physical functioning prior to hospitalization and at hospital discharge.

Return to work and lost earnings after acute respiratory distress syndrome: a 5-year prospective, longitudinal study of long-term survivors.

BACKGROUND: Delayed return to work is common after acute respiratory distress syndrome (ARDS), but has undergone little detailed evaluation. We examined factors associated with the timing of return to work after ARDS, along with lost earnings and shifts in healthcare coverage. METHODS: Five-year, multisite prospective, longitudinal cohort study of 138 2-year ARDS survivors hospitalised between 2004 and 2007. Employment and healthcare coverage were collected via structured interview. Predictors of time to return to work were evaluated using Fine and Grey regression analysis. Lost earnings were estimated using Bureau of Labor Statistics data. RESULTS: Sixty-seven (49%) of the 138 2-year survivors were employed prior to ARDS. Among 64 5-year survivors, 20 (31%) never returned to work across 5-year follow-up. Predictors of delayed return to work (HR (95% CI)) included baseline Charlson Comorbidity Index (0.77 (0.59 to 0.99) per point; p=0.04), mechanical ventilation duration (0.67 (0.55 to 0.82) per day up to 5 days; p<0.001) and discharge to a healthcare facility (0.49 (0.26 to 0.93); p=0.03). Forty-nine of 64 (77%) 5-year survivors incurred lost earnings, with average (SD) losses ranging from US$38 354 (21,533) to US$43 510 (25,753) per person per year. Jobless, non-retired survivors experienced a 33% decrease in private health insurance and concomitant 37% rise in government-funded coverage. CONCLUSIONS: Across 5-year follow-up, nearly one-third of previously employed ARDS survivors never returned to work. Delayed return to work was associated with patient-related and intensive care unit/hospital-related factors, substantial lost earnings and a marked rise in government-funded healthcare coverage. These important consequences emphasise the need to design and evaluate vocation-based interventions to assist ARDS survivors return to work.

Psychiatric symptoms after acute respiratory distress syndrome: a 5-year longitudinal study.

PURPOSE: We aimed to characterize anxiety, depression, and posttraumatic stress disorder (PTSD) symptoms over 5-year follow-up after acute respiratory distress syndrome (ARDS) and determine risk factors for prolonged psychiatric morbidity. METHODS: This prospective cohort study enrolled patients from 13 medical and surgical intensive care units in four hospitals, with follow-up at 3, 6, 12, 24, 36, 48, and 60 months post-ARDS. Trained research staff administered the Hospital Anxiety and Depression Scale (HADS) (scores ≥ 8 on anxiety and depression subscales indicating substantial symptoms) and the Impact of Event Scale-Revised (IES-R, scores ≥ 1.6 indicating substantial PTSD symptoms) at each follow-up visit. RESULTS: Of 196 consenting survivors, 186 (95%) completed HADS and IES-R assessments; 96 (52%) had any continuous or recurring (prolonged) symptoms, and 71 (38%), 59 (32%), and 43 (23%) had prolonged anxiety, depression, and PTSD symptoms, respectively (median total durations 33-39 months, 71-100% of observed follow-up time). Prolonged psychiatric symptoms tended to co-occur across domains; the most common morbidity pattern involved substantial symptoms in all three domains. Worse pre-ARDS mental health, including prior depression and psychological distress in the period immediately preceding ARDS, was strongly associated with prolonged post-ARDS psychiatric morbidity across symptom domains. CONCLUSIONS: Clinically significant and long-lasting symptoms of anxiety, depression, and PTSD are common in the first 5 years after ARDS. In-hospital screening of psychiatric history, including recent anxiety and depression symptoms, may be useful for long-term mental health treatment planning after ARDS.

Core Outcome Measures for Clinical Research in Acute Respiratory Failure Survivors. An International Modified Delphi Consensus Study.

RATIONALE: Research evaluating acute respiratory failure (ARF) survivors' outcomes after hospital discharge has substantial heterogeneity in terms of the measurement instruments used, creating barriers to synthesizing study data. OBJECTIVES: To identify a minimum set of core outcome measures that are essential to include in all clinical research studies evaluating ARF survivors after discharge. METHODS: We conducted a three-round modified Delphi consensus process with 77 participants (47% female, 55% outside the United States), including clinical researchers from more than 16 countries across six continents, patients/caregivers, clinicians, and research funders. Participants reviewed standardized information on measure instruments for seven consensus-derived outcomes plus one recommended outcome. MEASUREMENTS AND MAIN RESULTS: Response rates were 91 to 97% across the three rounds. Among 75 measurement instruments evaluated, the following met a priori consensus criteria: EQ-5D and 36-item Short Form Health Survey version 2 (optional) for the "satisfaction with life and personal enjoyment" and "pain" outcomes, and both the Hospital Anxiety and Depression Scale and the Impact of Events Scale-Revised for the "mental health" outcome. No measures reached consensus for the following outcomes: cognition, muscle and/or nerve function, physical function, and pulmonary function. All measures considered for pulmonary function met consensus criteria for exclusion. The following measures did not reach the threshold for consensus but achieved the highest scores for their respective outcomes: the Montreal Cognitive Assessment (cognition), manual muscle testing and handgrip dynamometry (muscle and/or nerve function), and 6-minute-walk test (physical function). CONCLUSIONS: This Core Outcome Measurement Set is recommended for use in all clinical research evaluating ARF survivors after hospital discharge. In the future, researchers should evaluate measures for outcomes not reaching consensus.

Core Domains for Clinical Research in Acute Respiratory Failure Survivors: An International Modified Delphi Consensus Study.

OBJECTIVES: To identify the "core domains" (i.e., patient outcomes, health-related conditions, or aspects of health) that relevant stakeholders agree are essential to assess in all clinical research studies evaluating the outcomes of acute respiratory failure survivors after hospital discharge. DESIGN: A two-round consensus process, using a modified Delphi methodology, with participants from 16 countries, including patient and caregiver representatives. Prior to voting, participants were asked to review 1) results from surveys of clinical researchers, acute respiratory failure survivors, and caregivers that rated the importance of 19 preliminary outcome domains and 2) results from a qualitative study of acute respiratory failure survivors' outcomes after hospital discharge, as related to the 19 preliminary outcome domains. Participants also were asked to suggest any additional potential domains for evaluation in the first Delphi survey. SETTING: Web-based surveys of participants representing four stakeholder groups relevant to clinical research evaluating postdischarge outcomes of acute respiratory failure survivors: clinical researchers, clinicians, patients and caregivers, and U.S. federal research funding organizations. SUBJECTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Survey response rates were 97% and 99% in round 1 and round 2, respectively. There were seven domains that met the a priori consensus criteria to be designated as core domains: physical function, cognition, mental health, survival, pulmonary function, pain, and muscle and/or nerve function. CONCLUSIONS: This study generated a consensus-based list of core domains that should be assessed in all clinical research studies evaluating acute respiratory failure survivors after hospital discharge. Identifying appropriate measurement instruments to assess these core domains is an important next step toward developing a set of core outcome measures for this field of research.

Healthcare Resource Use and Costs in Long-Term Survivors of Acute Respiratory Distress Syndrome: A 5-Year Longitudinal Cohort Study.

OBJECTIVE: To evaluate the time-varying relationship of annual physical, psychiatric, and quality of life status with subsequent inpatient healthcare resource use and estimated costs. DESIGN: Five-year longitudinal cohort study. SETTING: Thirteen ICUs at four teaching hospitals. PATIENTS: One hundred thirty-eight patients surviving greater than or equal to 2 years after acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Postdischarge inpatient resource use data (e.g., hospitalizations, skilled nursing, and rehabilitation facility stays) were collected via a retrospective structured interview at 2 years, with prospective collection every 4 months thereafter, until 5 years postacute respiratory distress syndrome. Adjusted odds ratios for hospitalization and relative medians for estimated episode of care costs were calculated using marginal longitudinal two-part regression. The median (interquartile range) number of inpatient admission hospitalizations was 4 (2-8), with 114 patients (83%) reporting greater than or equal to one hospital readmission. The median (interquartile range) estimated total inpatient postdischarge costs over 5 years were $58,500 ($19,700-157,800; 90th percentile, $328,083). Better annual physical and quality of life status, but not psychiatric status, were associated with fewer subsequent hospitalizations and lower follow-up costs. For example, greater grip strength (per 6 kg) had an odds ratio (95% CI) of 0.85 (0.73-1.00) for inpatient admission, with 23% lower relative median costs, 0.77 (0.69-0.87). CONCLUSIONS: In a multisite cohort of long-term acute respiratory distress syndrome survivors, better annual physical and quality of life status, but not psychiatric status, were associated with fewer hospitalizations and lower healthcare costs.

Health care resource use and costs of two-year survivors of acute lung injury. An observational cohort study.

RATIONALE: Survivors of acute lung injury (ALI) require ongoing health care resources after hospital discharge. The extent of such resource use, and associated costs, are not fully understood. OBJECTIVES: For patients surviving at least 2 years after ALI, we evaluated cumulative 2-year inpatient admissions and related costs, and the association of patient- and intensive care unit-related exposures with these costs. METHODS: Multisite observational cohort study in 13 intensive care units at four academic teaching hospitals evaluating 138 two-year survivors of ALI. MEASUREMENTS AND MAIN RESULTS: Two-year inpatient health care use data (i.e., admissions to hospitals, and skilled nursing and rehabilitation facilities) were collected for patients surviving at least 2 years, via (1) one-time retrospective structured interview with patient and/or proxy, (2) systematic medical record review for nonfederal study site hospitals, and (3) inpatient medical record review for non-study site hospitals, as needed for clarifying patient/proxy reports. Costs are reported in 2013 U.S. dollars. A total of 138 of 142 (97%) 2-year survivors completed the interview, with 111 (80%) reporting at least one inpatient admission during follow-up, for median (interquartile range [IQR]) estimated costs of $35,259 ($10,565-$81,166). Hospital readmissions accounted for 76% of costs. Among 12 patient- and intensive care unit-related exposures evaluated, baseline comorbidity and intensive care unit length of stay were associated with increased odds of incurring any follow-up inpatient costs. Having Medicare or Medicaid (vs. private insurance) was associated with median estimated costs that were 85% higher (relative median, 1.85; 95% confidence interval, 1.01-3.45; P=0.045). CONCLUSIONS: In this multisite study of 138 two-year survivors of ALI, 80% had one or more inpatient admission, representing a median (IQR) estimated cost $35,259 ($10,565-$81,166) per patient and $6,598,766 for the entire cohort. Hospital readmissions represented 76% of total inpatient costs, and having Medicare or Medicaid before ALI was associated with increased costs. With the aging population and increasing comorbidity, these findings have important health policy implications for the care of critically ill patients.

Personalized contact strategies and predictors of time to survey completion: analysis of two sequential randomized trials.

BACKGROUND: Effective strategies for contacting and recruiting study participants are critical in conducting clinical research. In this study, we conducted two sequential randomized controlled trials of mail- and telephone-based strategies for contacting and recruiting participants, and evaluated participant-related variables' association with time to survey completion and survey completion rates. Subjects eligible for this study were survivors of acute lung injury who had been previously enrolled in a 12-month observational follow-up study evaluating their physical, cognitive and mental health outcomes, with their last study visit completed at a median of 34 months previously. METHODS: Eligible subjects were contacted to complete a new research survey as part of two randomized trials, initially using a randomized mail-based contact strategy, followed by a randomized telephone-based contact strategy for non-responders to the mail strategy. Both strategies focused on using either a personalized versus a generic approach. In addition, 18 potentially relevant subject-related variables (e.g., demographics, last known physical and mental health status) were evaluated for association with time to survey completion. RESULTS: Of 308 eligible subjects, 67% completed the survey with a median (IQR) of 3 (2, 5) contact attempts required. There was no significant difference in the time to survey completion for either randomized trial of mail- or phone-based contact strategy. Among all subject-related variables, age ≤40 years and minority race were independently associated with a longer time to survey completion. CONCLUSION: We found that age ≤40 years and minority race were associated with a longer time to survey completion, but personalized versus generic approaches to mail- and telephone-based contact strategies had no significant effect. Repeating both mail and telephone contact attempts was important for increasing survey completion rate. TRIAL REGISTRATION: NCT00719446.

Repeated attempts using different strategies are important for timely contact with study participants.

OBJECTIVE: To study the effect of different mail- and phone-based strategies, along with patient- and research-related factors, on the time to contact with research participants. STUDY DESIGN AND SETTING: A prospective evaluation of a 12-week standardized protocol (embedded with two randomized trials of mail- and phone-based strategies) for contacting existing research participants for recruitment into a related study. RESULTS: Of 146 participants, 87 were eligible for contact via the standardized protocol, and 63 (72%) of these were successfully contacted within 12 weeks after multiple mail- and phone-based efforts. Using Cox proportional hazards regression analysis, the different mail and phone strategies showed no significant difference in the time to contact with participants. Of 34 patient- and research-related factors evaluated, only two were independently associated with time to contact among all 146 participants: (1) participants having their last visit conducted outside of the research clinic because of patient illness/condition had a longer time to contact and (2) those with a self-reported chronic fatigue history had a shorter time to contact. CONCLUSION: Few patient characteristics and research-related factors accurately predict time to contact. Repeated attempts using different strategies are important for successful and timely contact with study participants.