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Table 1 Overview of a-priori hypotheses (n = 63) and scores to accept these hypotheses

From: Construct validity of the OCTOPuS stratification algorithm for allocating patients with knee osteoarthritis into subgroups

RESEARCH QUESTION I: SIMILAR SUBGROUP PROPORTIONS
Subgroup proportion in one cohort is similar to subgroup proportion in total sample Deviation
‘Low muscle strength subgroup’
 AMS-OA [5] vs. total sample −10, + 10%1
 STABILO [17] vs. total sample −10, + 10%1
 NEXA [18] vs. total sample −10, + 10%1
 CBT [19] vs. total sample −10, + 10%1
 VIDEX (De Zwart AH, Dekker J, Roorda LD, van der Esch M, Lips P, van Schoor NM, et al.: High-intensity resistance training and vitamin D supplementation for knee osteoarthritis: a randomized controlled trial, Under review) vs. total sample −10, + 10%1
‘High muscle strength subgroup’
 AMS-OA [5] vs. total sample − 10, + 10%1
 STABILO [17] vs. total sample −10, + 10%1
 NEXA [18] vs. total sample −10, + 10%1
 CBT [19] vs. total sample −10, + 10%1
 VIDEX (De Zwart AH, Dekker J, Roorda LD, van der Esch M, Lips P, van Schoor NM, et al.: High-intensity resistance training and vitamin D supplementation for knee osteoarthritis: a randomized controlled trial, Under review) vs. total sample −10, + 10%1
‘Obesity subgroup’
 AMS-OA [5] vs. total sample − 10, + 10%1
 STABILO [17] vs. total sample −10, + 10%1
 NEXA [18] vs. total sample −10, + 10%1
 CBT [19] vs. total sample −10, + 10%1
 VIDEX (De Zwart AH, Dekker J, Roorda LD, van der Esch M, Lips P, van Schoor NM, et al.: High-intensity resistance training and vitamin D supplementation for knee osteoarthritis: a randomized controlled trial, Under review) vs. total sample -10, + 10%1
RESEARCH QUESTION 2: CHARACTERISTICS IN LINE WITH UNDERLYING PHENOTYPES
Characteristic in one subgroup that is in line with proposed underlying phenotype is different from other subgroups p-value
‘Low muscle strength subgroup’ (‘age-induced phenotype’)
 Higher age, compared to:
  ‘high muscle strength subgroup’ P < 0.052
  ‘obesity subgroup’ P < 0.052
 Lower muscle strength, compared to:
  ‘high muscle strength subgroup’ P < 0.052
  ‘obesity subgroup’ P < 0.052
High muscle strength subgroup’ (‘post-traumatic phenotype’)
 More history of knee surgery, compared to:
  ‘low muscle strength subgroup’ P < 0.052
  ‘obesity subgroup’ P < 0.052
 Higher muscle strength, compared to:
  ‘low muscle strength subgroup’ P < 0.052
  ‘obesity subgroup’ P < 0.052
 More males, compared to:
  ‘low muscle strength subgroup’ P < 0.052
  ‘obesity subgroup’ P < 0.052
 Younger age, compared to:
  ‘low muscle strength subgroup’ P < 0.052
  ‘obesity subgroup’ P < 0.052
 Higher K/L grade, compared to:
  ‘low muscle strength subgroup’ P < 0.052
  ‘obesity subgroup’ P < 0.052
 Less comorbidities, compared to:
  ‘low muscle strength subgroup’ P < 0.052
  ‘obesity subgroup’ P < 0.052
 Less severe knee pain, compared to:
  ‘low muscle strength subgroup’ P < 0.052
  ‘obesity subgroup’ P < 0.052
 Less impaired physical function, compared to:
  ‘low muscle strength subgroup’ P < 0.052
  ‘obesity subgroup’ P < 0.052
‘Obesity subgroup’ (‘metabolic phenotype’)
 Higher BMI, compared to:
  ‘high muscle strength subgroup’ P < 0.052
  ‘low muscle strength subgroup’ P < 0.052
 More comorbidities, compared to:
  ‘high muscle strength subgroup’ P < 0.052
  ‘low muscle strength subgroup’ P < 0.052
 Lower muscle strength, compared to:
  ‘high muscle strength subgroup’ P < 0.052
  ‘low muscle strength subgroup’ P < 0.052
 More severe knee pain, compared to:
  ‘high muscle strength subgroup’ P < 0.052
  ‘low muscle strength subgroup’ P < 0.052
 More severe impaired physical function, compared to:
  ‘high muscle strength subgroup’ P < 0.052
  ‘low muscle strength subgroup’ P < 0.052
RESEARCH QUESTION 3: EFFECTS OF USUAL EXERCISE THERAPY IN LINE WITH HYPOTHESIZED EFFECTS
  Effect size/ % with MIC
Large effects in ‘low muscle strength subgroup’
 Large effect size on knee pain 0.8 ± 0.2
 Majority with MIC on knee pain >  67%
 Large effect size on physical function 0.8 ± 0.2
 Majority with MIC on physical function >  67%
 Large effect size on muscle strength 0.8 ± 0.2
 Majority with MIC on muscle strength <  67%
Medium effects in ‘obesity subgroup’
 Medium effect size on knee pain 0.5 ± 0.2
 Half with MIC on knee pain 33–67%
 Medium effect size on physical function 0.5 ± 0.2
 Half with MIC on physical function 33–67%
 Medium effect size on muscle strength 0.5 ± 0.2
 Half with MIC on muscle strength 33–67%
Small effects in ‘high muscle strength subgroup’
 Small effect size on knee pain 0.2 ± 0.2
 Minority with MIC on knee pain <  33%
 Small effect size on physical function 0.2 ± 0.2
 Minority with MIC on physical function <  33%
 Small effect size on muscle strength 0.2 ± 0.2
 Minority with MIC on muscle strength <  33%
  1. MIC = minimal important change; 1 difference in subgroup proportion (%)in one cohort compared to subgroup proportion in total sample; 2 p-value for differences between subgroups; 3 isokinetic knee extensor strength measure as outcome; 4 30-s chair stand test as outcome; *significant finding in the opposite direction as expected, therefore hypothesis not accepted