The recommendations are graded by their level (I, II) and strength (A, B, C+, C, D, D+, D-) of evidence. Definitions for the level and strength of the recommendations are presented at the end of the "Major Recommendations" field.
Clinical Practice Guidelines for Intensity and Organization of Rehabilitation
Stroke unit versus general ward, level I (randomized controlled trial [RCT]) and level II (controlled clinical trial [CCT]): Grade A for length of stay at end of treatment, 2 weeks, and follow-up, 3 years (clinically important benefit demonstrated); grade B for mobility (number of patients able to walk long distances independently) at end of treatment, 6 weeks (clinically important benefit demonstrated); grade C+ for functional status (number of patients with mild-moderate impairment) at follow-up, 1 year (clinically important benefit demonstrated without statistical significance); grade C for functional status (number of patients deteriorated in activities of daily living (ADL) score) at end of treatment, 3 months, and follow-up, 6 months, functional status (number of patients independent in ADL) at end of treatment, 6 weeks, length of stay (in days) at end of treatment, 6 weeks and 3 months, mobility (number of patients independent in walking mobility) at end of treatment, 16 weeks, mobility (number of patients independent in walking [Barthel Index], number of patients independent in indoor and outdoor walking [Rivermead ADL Scale–self-care], number of patients independent in walking outside and climbing stairs [Rivermead ADL Scale–household]) at end of treatment, 3 and 6 months, motor function (number of patients independent in upper extremity and lower extremity function) at end of treatment, 16 weeks, efficiency at end of treatment, 2 weeks, postural status (number of patients sitting and standing) at follow-up, 6 weeks, functional status (ADL score) at end of treatment, 3 months, and follow-up, 9 months, and resource cost (total cost per patient in thousands of dollars) at follow-up, 1 year (no benefit demonstrated); grade D for mobility (number of patients able to walk short distances with or without aids) at end of treatment, 6 weeks, functional status (number of functional patients) at follow-up, 1 year, and resource cost (number of physician visits per patient) at follow-up, 1 year (no benefit demonstrated but favoring control); grade D+ for functional status (ADL score) at end of treatment, 1 week (clinically important benefit favoring control demonstrated without statistical significance). Patients with acute, subacute, postacute, and chronic stroke.
Stroke unit versus home care, level I (RCT): Grade A for functional status (number of patients independent with Barthel) at follow-up, 9 months (clinically important benefit demonstrated); grade C for functional status (number of patients independent with Modified Rankin score) at end of treatment, 3 months, and follow-up, 9 months, and functional status (number of patients independent with Barthel) at end of treatment, 3 months (no benefit demonstrated). Patients with acute stroke.
Stroke unit (large artery stroke) versus general ward (large artery stroke), level I (RCT): Grade A for functional status at follow-up, 1 year, and quality of life at follow-up, 3 months (clinically important benefit demonstrated); grade C for functional status at follow-up, 3 months, and quality of life at follow-up, 3 months (no benefit demonstrated); grade D for length of stay at follow-up, 3 months (no benefit demonstrated but favoring control); grade D- for efficiency at follow-up, 3 months (clinically important benefit favoring control demonstrated with statistical significance). Patients with acute stroke.
Stroke unit (small artery stroke) versus general ward (small artery stroke), level I (RCT): Grade A for quality of life at follow-up, 3 months (clinically important benefit demonstrated); grade C for quality of life at follow-up, 1 year (no benefit demonstrated); grade D for functional status at follow-up, 3 months, and 1 year (no benefit demonstrated but favoring control); grade D- for length of stay and efficiency at follow-up, 3 months (clinically important benefit favoring control demonstrated with statistical significance). Patients with acute stroke.
Intensive outpatient physiotherapy rehabilitation program versus control group, level I (RCT): Grade C+ for quality of life at end of treatment, 3 months (clinically important benefit demonstrated without statistical significance); grade C for functional status at end of treatment, 3 months (no benefit demonstrated); grade D for functional status at follow-up, 6 months (no benefit demonstrated but favoring control). Patients with chronic stroke.
Six days/week versus seven days/week treatment, level I (RCT): Grade C+ for mobility at end of treatment, 3 weeks (clinically important benefit demonstrated without statistical significance); grade C for functional status and length of stay at end of treatment, 3 weeks (no benefit demonstrated). Patients with post-acute stroke.
Enhanced occupational therapy versus standard customary occupational therapy, level I (RCT): Grade A for functional status (number of patients improved in ADL) at end of treatment, 8 weeks and 6 months, life habit/leisure (overall leisure score) at end of treatment, 3 and 6 months, life habit/leisure (total leisure score) at end of treatment, 6 months, mobility (Nottingham Extended Activities of Daily Living [EADL] score for mobility) at end of treatment, 3 and 6 months, functional status (Nottingham EADL score) at end of treatment, 8 weeks, 3 months, and 6 months (clinically important benefit demonstrated); grade C+ for quality of life (number of patients living independently) and functional status (functional independence measures [FIM] for upper extremity and lower extremity dressing) at end of treatment, 3 weeks, and functional status (EADL total score) at follow-up, 3 months (clinically important benefit demonstrated without statistical significance); grade C for life habit/leisure (total leisure score) and mobility (Nottingham Health Profile [NHP] score for mobility) at end of treatment, 6 months, functional status (Barthel Index score) at follow-up, 3 months (no benefit demonstrated); grade D for mobility (NHP score for mobility) at end of treatment, 3 months (no benefit demonstrated but favoring control); grade D+ for pain relief at end of treatment, 3 months and 6 months, and quality of life (General Health Questionnaire) at follow-up, 3 months (clinically important benefit favoring control demonstrated without statistical significance). Patients with subacute stroke.
Enhanced occupational therapy versus no therapy, level I (RCT): Grade A for mobility (NHP score for mobility and Nottingham EADL for mobility) at end of treatment, 3 months and 6 months, life habit/leisure (overall leisure score and total leisure activity) at end of treatment, 3 and 6 months, functional status (number of patients improved in ADL) at follow-up, 6 months (clinically important benefit demonstrated); grade C+ for activity involvement (Katz Adjustment Index: number of patients satisfied with their walking) at follow-up, 13 weeks, activity involvement (number of patients satisfied with their work in the yard) at end of treatment, 5 weeks, and functional status (EADL) at follow-up, 1 year (clinically important benefit demonstrated without statistical significance); grade C for functional status (Barthel ADL Index) at follow-up, 6 months and 1 year, functional status (EADL) at follow-up, 6 months, activity involvement (number of patients satisfied with their work in and around the house and number of patients satisfied with their walking) at end of treatment, 5 weeks, and activity involvement (number of patients satisfied with their work in the yard) at follow-up, 13 weeks (no benefit demonstrated); grade D for activity involvement (number of patient satisfied with their work in and around house) at follow-up, 13 weeks (no benefit demonstrated but favoring control); grade D+ for pain relief at end of treatment, 3 and 6 months (clinically important benefit favoring control demonstrated without statistical significance). Patients with subacute stroke.
Standard customary occupational therapy versus no therapy, level I (RCT): Grade A for functional status (EADL score) at follow-up, 1 month (clinically important benefit demonstrated); grade C+ for mobility (NHP for mobility) at end of treatment, 3 and 6 months, for pain relief at end of treatment, 3 months (clinically important benefit demonstrated without statistical significance); grade C for life habit/leisure (overall leisure score and total leisure activity score) at end of treatment, 3 and 6 months, for functional status (Barthel Index score) at follow-up, 1 month, pain relief at end of treatment, 6 months (no benefit demonstrated); grade D for quality of life at follow-up, 1 month (no benefit demonstrated but favoring control); grade D+ for functional status (EADL score for mobility) at end of treatment, 3 months and 6 months (clinically important benefit favoring control demonstrated without statistical significance). Patients with subacute stroke.
Enhanced physiotherapy (60-minute treatment of physiotherapy) versus standard customary physiotherapy care (30 minutes), level I (RCT): Grade C for quality of life at end of treatment, 6 weeks (no benefit demonstrated); grade D for quality of life at end of treatment, 6 months (no benefit demonstrated but favoring control). Patients with chronic stroke.
Enhanced physiotherapy versus standard customary physiotherapy treatment, level I (RCT): Grade A for motor function (Action Research Arm Test [ARAT]) at follow-up, 21 weeks (clinically important benefit demonstrated); grade C+ for functional status (Barthel Index) at follow-up, 3 and 16 weeks (clinically important benefit demonstrated without statistical significance); grade C for functional status (Barthel Index) at end of treatment, 5 weeks, and follow-up, 21 weeks, functional status (EADL score) at follow-up, 16 weeks and 21 weeks, motor function (Rivermead Motor Assessment–upper extremity) at end of treatment, 5 weeks, and follow-up, 21 weeks, motor function (Ten-Hole Peg Test) at end of treatment, 5 weeks, and follow-up, 16 weeks, and motor function (ARAT) at end of treatment, 5 weeks (no benefit demonstrated); grade D for functional status (EADL score) at end of treatment, 5 weeks (no benefit demonstrated but favoring control); grade D+ for motor function (Rivermead Motor Assessment–gross function) at follow-up, 3 weeks, and grip strength (maximum grip) at follow-up, 16 weeks (clinically important benefit favoring control demonstrated without statistical significance); grade D- for motor function (Rivermead Motor Assessment-upper extremity) at follow-up, 3 weeks and 16 weeks, motor function (ARAT) at follow-up, 16 weeks, motor function (Rivermead Motor Assessment–gross function) at end of treatment, 5 weeks, and follow-up, 16 weeks, and grip strength (maximum grip) at end of treatment, 5 weeks, and follow-up, 3 weeks (clinically important benefit favoring control demonstrated with statistical significance). Patients with subacute stroke.
Enhanced assistant physiotherapist versus standard customary physiotherapy treatment, level I (RCT): Grade A for motor function (Rivermead Motor Assessment-upper extremity) at follow-up, 21 weeks, motor function (ARAT) at end of treatment, 5 weeks, and follow-up, 21 weeks (clinically important benefit demonstrated); grade C+ for functional status (Barthel Index) at follow-up, 3 and 16 weeks, functional status (EADL) at end of treatment, 5 weeks, and follow-up, 21 weeks, motor function (ARAT) at follow-up, 16 weeks (clinically important benefit demonstrated without statistical significance); grade C for functional status (Barthel Index) at end of treatment, 5 weeks, functional status (EADL score) at follow-up, 16 weeks, motor function (Rivermead Motor Assessment-upper extremity) at end of treatment, 5 weeks, and follow-up, 16 weeks, motor function (Rivermead Motor Assessment–gross function) at follow-up, 3 and 16 weeks, motor function (Ten-Hole Peg Test) at end of treatment, 5 weeks, and follow-up, 16 weeks (no benefit demonstrated); grade D for functional status (Barthel Index) at follow-up, 21 weeks (no benefit demonstrated but favoring control); grade D+ for motor function (Rivermead Motor Assessment-upper extremity) at follow-up, 3 weeks, and grip strength (maximum grip) at end of treatment, 5 weeks, and follow-up, 16 weeks (clinically important benefits favoring control demonstrated without statistical significance); grade D- for motor function (Rivermead Motor Assessment–gross function) at end of treatment, 5 weeks, and grip strength (maximum grip) at follow-up, 3 weeks (clinically important benefit favoring control demonstrated with statistical significance). Patients with subacute stroke.
Enhanced physiotherapy versus enhanced assistant physiotherapist treatment, level I (RCT): Grade A for motor function (Rivermead Motor Assessment–gross function) at end of treatment, 5 weeks, grip strength (maximum grip) at follow-up, 3 weeks, and motor function (ARAT) at follow-up, 21 weeks (clinically important benefit demonstrated); grade A favoring enhanced assistant physiotherapist for functional status (Barthel Index) at end of treatment, 5 weeks, motor function (Rivermead Motor Assessment–upper extremity) at follow-up, 16 weeks and 21 weeks, functional status (EADL score) at follow-up, 21 weeks, motor function (ARAT) at end of treatment, 5 weeks, and follow-up, 16 weeks (clinically important benefit demonstrated); grade C+ for motor function (Rivermead Motor Assessment–gross function) at follow-up, 16 weeks (clinically important benefit demonstrated without statistical significance); grade C+ favoring enhanced assistant physiotherapist for functional status (Barthel Index) at follow-up, 3 and 16 weeks, functional status (EADL) at end of treatment, 5 weeks, motor function (Rivermead Motor Assessment–upper extremity) at follow-up, 3 weeks, grip strength at end of treatment, 5 weeks, and follow-up, 16 weeks (clinically important benefit demonstrated without statistical significance); grade C for functional status (Barthel Index) at follow-up, 21 weeks, functional status (EADL score) at follow-up, 16 weeks, motor function (Rivermead Motor assessment–upper extremity) at end of treatment, 5 weeks, and motor function (Ten-Hole Peg Test) at end of treatment, 5 weeks, and follow-up, 16 weeks (no benefit demonstrated). Patients with subacute stroke.
Enhanced upper-extremity treatment versus interdisciplinary treatment, level I (RCT): Grade A for motor function (Frenchay Arm Test) and functional status (Barthel Index) at follow-up, 18 weeks (clinically important benefit demonstrated); grade C for motor function (Upper Limb Motricity Index and Frenchay Arm Test) at follow-up, 6 weeks, functional status (Nottingham EADL) at follow-up, 18 weeks, and functional status (Barthel Index) at follow-up, 6 weeks (no benefit demonstrated); grade D for motor function (Upper Limb Motricity Index) at follow-up, 18 weeks, functional status (Nottingham EADL) at follow-up, 6 weeks (no benefit demonstrated but favoring control); grade D+ for motor function (ARAT) at follow-up, 6 and 18 weeks (clinically important benefit favoring control demonstrated without statistical significance). Patients with subacute stroke.
Enhanced therapy (severe stroke) versus standard customary care (severe stroke), level I (RCT): Grade D for mobility at end of treatment, 6 months (no benefit demonstrated). Patients with acute stroke.
Enhanced therapy (mild stroke) versus standard customary care (mild stroke), level I (RCT): Grade D for mobility at end of treatment, 6 months (no benefit demonstrated). Patients with acute stroke.
Home therapy (physiotherapy) versus standard customary care without home visits, level I (RCT): Grade C+ for functional status (Instrumental Activities of Daily Living [IADL]–domestic activities) at follow-up, 6 months (clinically important benefit demonstrated without statistical significance); grade C for discharge disposition, functional status, mobility, and life habits/leisure at follow-up, 6 months (no benefit demonstrated). Patients with chronic stroke.
Home-based physiotherapy at high-intensity versus low-intensity physiotherapy control, level I (RCT): Grade A for motor function (STroke REhabilitation Assessment of Movement [STREAM] lower extremity) at follow-up, 11 weeks (clinically important benefit demonstrated); grade C+ functional status and motor function (STREAM–upper extremity) at follow-up, 11 weeks (clinically important benefit demonstrated without statistical significance); grade C for mobility at follow-up, 11 weeks, functional status and motor function (STREAM–upper extremity) at follow-up, 22 weeks (no benefit demonstrated); grade D for mobility at follow-up, 22 weeks (no benefit demonstrated but favoring control); grade D+ for motor function (STREAM–lower extremity) at follow-up, 22 weeks (clinically important benefit favoring control demonstrated without statistical significance). Patients with chronic stroke.
Home-based rehabilitation versus hospital-based rehabilitation, levels I and II (RCT, CCT): Grade C for resource cost at follow-up, 1 year, and mobility and functional status at end of treatment, 3 months (no benefit demonstrated). Patients with post-acute and chronic stroke.
Rehabilitation versus no rehabilitation group, level II (CCT): Grade D for motor function at end of treatment, 6 months (no benefit demonstrated but favoring control); grade D+ for functional status at end of treatment, 6 months (clinically important benefit favoring control demonstrated without statistical significance). Patients with subacute stroke.
Home therapy (physician) versus standard customary care without home visits, level I (RCT): Grade A for decrease in hospital readmissions and functional status (Frenchay Activities Index [FAI]) at follow-up, 6 months (clinically important benefit demonstrated); grade C for functional status (Functional Quality of Movement Scale [FQM]) motor performance, Barthel Index, EADL–personal daily care, IADL–domestic activities), mobility and life habits/leisure at follow-up, 6 months (no benefit demonstrated); grade D for functional status (FQM quality of movement) at follow-up, 6 months (no benefit demonstrated but favoring control). Patients with chronic stroke.
Home therapy (physician) versus home therapy (physiotherapy), level I (RCT): Grade C+ favoring home therapy (physiotherapy) for functional status (IADL–domestic activities) at follow-up, 6 months (clinically important benefit demonstrated without statistical significance); grade C for decrease in hospital readmission, functional status (Frenchay Activities Index, FQM motor performance, FQM quality of movement, Barthel Index, and EADL–personal daily care), mobility and life habits/leisure at follow-up, 6 months (no benefit demonstrated). Patients with chronic stroke.
Extended stroke unit service with early supported discharge versus ordinary stroke unit service, level I (RCT): Grade A for functional status (number of patients with Rankin score less than 2) at follow-up, 6 months (clinically important benefits demonstrated); grade C+ for physical mobility at follow-up, 3 weeks and 1 year (clinically important benefits demonstrated without statistical significance); grade C for functional status (number of patients with Barthel Index score higher than 95) at follow-up, 3 weeks, 6 months, and 1 year, for discharge status and preventing mortality at follow-up, 1 year, for energy level and pain at follow-up, 3 weeks, 6 months, and 1 year, for global health status at follow-up, 1 year, and functional status (number of patients with Rankin score less than 2) at follow-up, 3 weeks and 1 year (no benefit demonstrated); grade D for global health status at follow-up, 3 weeks and 6 months (no benefit demonstrated but favoring control); grade D+ for physical mobility at follow-up, 6 months (clinically important benefits demonstrated without statistical significance favoring control). Patients with acute stroke.
Early physiotherapy intervention versus control group, level I (RCT): Grade C+ for functional status (Modified Barthel Index) and motor function (Fugl-Meyer score for lower extremity) at end of treatment, 1 month, and follow-up, 5 months, and motor function (Fugl-Meyer score for upper extremity) at end of treatment, 1 month (clinically important benefits demonstrated without statistical significance);
grade D for motor function (Fugl-Meyer score for upper extremity) at follow-up, 5 months (no benefit demonstrated but favoring control). Patients with acute stroke.
Home-based exercise training versus control, level I (RCT): Grade A for change in gait speed, gait endurance, torque (change in knee isometric extensors), endurance, and cardiopulmonary function at end of treatment, 12 weeks; grade C+ for motor function (change in Fugl-Meyer lower extremity), change in gait speed, gait endurance, functional status (Physical Function Index), and strength (change in grip strength) at end of treatment, 12 weeks (clinically important benefit demonstrated without statistical significance); grade C for motor function (change in Fugl-Meyer upper extremity and lower extremity), balance (Berg balance and change in Berg balance), functional status (IADL and Barthel ADL Index) at end of treatment, 12 weeks (no benefit demonstrated); grade D+ for balance (Functional reach) at end of treatment, 12 weeks (clinically important benefit favoring control demonstrated without statistical significance); grade D for torque (change in ankle isometric dorsiflexors; no benefit demonstrated but favoring control). Patients with post-acute stroke.
Outpatient versus home exercise group, level I (RCT): Grade C+ favoring home exercise group for gait speed at end of treatment, 6 months, and follow- up, 3 months (clinically important benefit demonstrated without statistical significance); grade C for single support time at end of treatment, 6 months, and follow-up, 3 months (no benefit demonstrated). Patients with chronic stroke.
Outpatient versus control, level I (RCT): Grade D for gait speed at follow-up, 3 months (no benefit demonstrated but favoring control); grade D+ for gait speed at end of treatment, 6 months, and single support time at end of treatment, 6 months, and follow-up, 3 months (clinically important benefit demonstrated without statistical significance). Patients with chronic stroke.
Outpatient therapy versus home therapy, level I (RCT): Grade C for grip strength on affected side and motor assessment, functional status, and gait speed at end of treatment, 6 weeks and 3 months (no benefit demonstrated). Patients with subacute stroke.
Home physiotherapy versus day-hospital group, level I (RCT): Grade A for resource cost at end of treatment, 8 weeks (clinically important benefit demonstrated). Patients with subacute stroke.
Home-exercise versus control group, level I (RCT): Grade C for gait speed at end of treatment, 6 months, and follow-up, 3 months (no benefit demonstrated); grade D for single support time at end of treatment, 6 months, and follow-up, 3 months (no benefit demonstrated but favoring control). Patients with chronic stroke.
Home therapy versus control group, level II (CCT): Grade C for motor function at end of treatment, 9 weeks (no benefit demonstrated). Patients with subacute stroke.
Combined outpatients and home exercise versus control group, level I (RCT): Grade C for gait speed at end of treatment, 6 months, and follow-up, 3 months (no benefit demonstrated); grade D for single support time at end of treatment, 6 months, and follow-up, 3 months (no benefit demonstrated but favoring control). Patients with chronic stroke.
Early care versus standard customary care in stroke unit, level I (RCT): Grade A for length of stay at end of treatment, 6 weeks (clinically important benefit demonstrated); grade C for mobility and functional status at end of treatment, 6 weeks (no benefit demonstrated). Patients with acute stroke.
Early supported discharge with home rehabilitation versus standard customary rehabilitation, level I (RCT): Grade A for functional status (Older Americans Resource Scale for Instrumental ADL) at end of treatment, 1 and 3 months, and length of stay at follow-up, 3 months (clinically important benefit demonstrated); grade C for motor function and mobility at end of treatment, 1 and 3 months, quality of life at follow-up, 6 months, functional status (Barthel Index) and pain relief at end of treatment, 3 months (no benefit demonstrated); grade D for functional status (Nottingham EADL score) at end of treatment, 3 months, and follow-up, 6 months, quality of life at end of treatment, 3 months, pain relief and functional status (Barthel Index) at end of treatment, 1 month (no benefit demonstrated but favoring control). Patients with acute stroke.
Early supported discharge versus standard customary rehabilitation, level I (RCT): Grade A for length of stay and quality of life (Dartmouth Coop Global Health Status–total) at end of treatment, 3 months, and functional status (Nottingham EADL) at follow-up, 3 months (clinically important benefit demonstrated); grade C for motor function and functional status (Rivermead ADL score) at follow-up, 9 months, gait speed and functional status (Barthel ADL Index) at end of treatment, 3 months, and follow-up, 9 months, and quality of life (Dartmouth Coop Global Health Status–physical fitness, daily activities, and pain relief) at end of treatment, 3 months (no benefit demonstrated); grade D for motor function and functional status (Nottingham ADL) at end of treatment, 3 months (no benefit demonstrated but favoring control); grade D+ for functional status (Nottingham ADL) at follow-up, 9 months (clinically important benefit favoring control demonstrated without statistical significance). Patients with acute and post-acute stroke.
Home intervention (rehabilitation and nursing services) versus standard customary care, level I (RCT): Grade A for resource cost at follow-up, 3 months (clinically important benefit demonstrated); grade C for quality of life at follow-up, 3 months (no benefit demonstrated). Patients with subacute stroke.
Nursing early activation program versus no therapy, level I (RCT): Grade C for mobility and functional status at follow-up, 1 year (no benefit demonstrated). Patients with acute stroke.
Integrated care pathway versus standard customary multidisciplinary team care, level I (RCT):
Grade C for functional status (number of patients with no problems with self-care, number of patients with no problems with usual activities) and pain relief at end of treatment, 6 months (no benefit demonstrated); grade D for mobility, functional status (number of patients with some problems with usual activities), and pain relief at end of treatment, 6 months (no benefits demonstrated but favoring control); grade D+ for functional status (number of patients with some problems with washing and dressing) at end of treatment, 6 months (clinically important benefit favoring control demonstrated without statistical significance). Patients with acute stroke.
Full-time integrated treatment (FIT) versus standard customary rehabilitation, level II (CCT): Grade C for functional status at end of treatment, 4 weeks and 6 weeks, and length of stay at end of treatment, 4 weeks (no benefit demonstrated). Patients with acute stroke.
Critical path method versus standard customary care method, level I (RCT): Grade C for functional status (FIM motor subscale) at end of treatment, 1 month (no benefit demonstrated); grade D for functional status (FIM raw score) and length of stay at end of treatment, 1 month (no benefit demonstrated but favoring control). Patients with acute stroke.
Structured nursing intervention versus conventional rehabilitation, level I (RCT): Grade C for functional status (FIM and IADL) and self-perception of health at end of treatment, 3 months, and follow-up, 3 months (no benefit demonstrated). Patients with acute stroke.
Home hospitalization versus standard stroke care (inpatient), level I (RCT): Grade D for neurological status and functional status at follow-up, 6 months (no benefit demonstrated but favoring control). Patients with acute stroke.
Definitions:
Level of Evidence
Level I: Randomized controlled trials
Level II: Nonrandomized studies
Grade of Recommendation
Grade A: Evidence from one or more randomized controlled trials (RCTs) of a statistically significant, clinically important benefit (>15%)
Grade B: Statistically significant, clinically important benefit (>15%), if the evidence was from observational studies or controlled clinical trials (CCTs)
Grade C+: Evidence of clinical importance (>15%) but not statistical significance
Grade C: Interventions where an appropriate outcome was measured in a study that met the inclusion criteria, but no clinically important difference and no statistical significance were shown
Grade D: Evidence from one or more randomized controlled trials of a statistically significant benefit favoring the control group (<0%: favors controls)
Grade D+: Evidence of clinical importance (<-15% for controls) without statistical significance
Grade D-: Evidence from one or more randomized controlled trials of a clinically important benefit (<-15% for controls) that was statistically significant, where the number of participants in the study is equal to or higher than 100
