Table 1.

Results of convergent mixed-methods analysis presented using implementation outcome framework with associated implications for a future RCT

Implementation Outcome	Quantitative Results	Qualitative Results with Example Quotes	Implication for Future RCT
Acceptability of an RCT evaluating APPS	57% of clinicians perceive randomization to control group unacceptable	Clinicians report perceived lack of equipoise for prone positioning, lack of alternatives: “[Avoiding proning] is a little bit more challenging to me because we obviously don’t have a lot of things that work for COVID…I think a lot of the patients do respond to going to a prone position as far as their oxygen saturation levels, so, telling people to not do that, I do have a little hesitation with that.”	May hinder recruitment or lead to selection bias; consider clinician education strategy or switch to nontraditional (e.g., quasi-experimental) trial design
Adoption of an RCT evaluating APPS	74% of physicians assigned to APPS prescribed the intervention to eligible patients		May require modifying intervention to encourage uptake, anticipate dilution of treatment effect in intention-to-treat analyses
Appropriateness of an RCT evaluating APPS	71% of clinicians reported that trial intervention has become usual care		Consider organizational education strategy to reinforce equipoise or quasi-experimental design
Effectiveness of an RCT evaluating APPS	Direction of research outcomes favored prone positioning. 100% of respondents endorsed ICU use and/or advanced respiratory support rates to be relevant and patient-centered primary outcome	Patients subjectively felt that prone positioning improved their breathing: “I mean, [proning] did work.” “Yes. [Proning] actually helps, a lot.” “Thank God, I feel better now.”	Further investigation of prone positioning for nonintubated patients in larger studies likely warranted; potential patient-centered outcomes might include ICU or advanced respiratory support use
Equity of an RCT evaluating APPS	Lower rates of adherence among Black (19%) compared with white (56%) and non-Black Hispanic (71%) patients		Develop culturally tailored approaches to reduce disparities in adherence
Feasibility of an RCT evaluating APPS	95% enrollment rate (only 2 patients met exclusion criteria). 98% of patients completed the study. Only 2 of 27 patients had documentation of prone position duration. Outcome data collection: no missing data for ICU transfer, advanced respiratory support, or mortality	Nurses reported adherence to a strict positioning schedule to be challenging owing to complexities of care environment: “Working on the COVID unit is just so unpredictable and everybody can be fine one minute and the next they are not. So, we could say at 2:00 we are going to prone all of our patients for 1 h; however, at 2:00, everything can go awry and we get nobody proned, and then it would be completely off schedule.…So, there would definitely be a lot of challenges to it.”	Tailor strategies to reduce complexity and increase flexibility of the intervention delivery protocol. Traditional RCTs with active data collection or novel approaches such as smart phone applications and patient-reported measures will be needed if reliable estimates of prone duration are desired. Otherwise, pragmatic trials should not plan specific analyses around these data
Fidelity of an RCT evaluating APPS	50% of patients had protocol violations/crossovers. 0% of patients managed the 12- to 16-h prone target time suggested by clinicians. Patients estimated spending between 10 and 120 min a day in prone position	Patients perceived prone positioning to be difficult: “Just that at the time, in the condition that my body was in, I could not bear it for too long with my back pain. So, I had to turn a lot.”	Will require strategies to enhance organizational and individual buy-in and improve comfort/tolerability. Consider more flexible prone time targets than those recommended in mechanically ventilated patients. Anticipate dilution of treatment effect, plan education strategy to clinicians to limit crossovers
Penetration of an RCT evaluating APPS	No patients experienced intubation or death during hospitalization		Adapt recruitment strategies, may require inclusion of nonintubated patients admitted to ICU

Definition of abbreviations: APPS = Awake Prone Positioning Strategy; COVID = coronavirus disease; ICU = intensive care unit; RCT = randomized controlled trial.