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Table 4 Methods for managing clustering and learning by analysis

From: Managing clustering effects and learning effects in the design and analysis of multicentre randomised trials: a survey to establish current practice

Question

Category

Response statistics

n

N

n/N%

6

a

Assuming that you have stratified by centre, do you combine by the stratification factor for the purpose of analysis? If so how?

See Table5for further details.

Yes

24

44

55%

 Pre-specified grouping rules at design stage

19

24

80%

 Ad hoc approach, e.g. determined after design due to small numbers per group

14

24

58%

 Other grouping rule or further details provided

6

24

26%

No

17

44

39%

No response

3

44

7%

b

Assuming that you have stratified by treatment provider, do you combine by the stratification factor for the purpose of analysis? If so how?

Yes

16

44

36%

 Pre-specified grouping rules at design stage

12

16

75%

 Ad hoc approach, e.g. determined after design due to small numbers per group

7

16

44%

See Table5for further details.

 Other grouping rule or further details provided

5

16

31%

No

14

44

32%

No experience with trials of this type

1

44

2%

No response

13

44

30%

7

Does your Unit include centre in the statistical model when comparing treatment?

Yes

39

44

89%

 But only if it was used to stratify randomisation

18

39

46%

 Always

6

39

15%

 Sometimesa

15

39

38%

No, never

3

44

7%

No responseb

2

44

5%

a

If yes, and assuming that the sample size allows either, would you treat this effect as fixed or random?

See Supplementary Box3for further details.

Fixed or random, depending on circumstances

14

39

36%

Fixed

11

39

28%

Random

12

39

31%

No response

2

39

5%

8

Does your Unit include treatment provider in the statistical model when comparing treatment?

Yes

26

44

59%

 But only if it was used to stratify randomisation

8

26

31%

See Supplementary Box4for further details.

 Always

0

26

0%

 Sometimesc

18

26

69%

No, never

13

46

30%

No responsed

5

44

11%

a

If yes, and assuming that the sample size allows either, would you treat this effect as fixed or random?

Fixed or random, depending on circumstances

4

26

15%

Fixed

2

26

8%

Random

18

26

69%

No response

2

26

8%

b

If yes, has this effect ever been treated as time-varying within the statistical model?

Yes

2

26

8%

No

21

26

81%

No response

3

26

12%

9

In each of the following scenarios, regardless of the randomisation stratification approach, has a treatment by centre or surgeon interaction investigated, in trials that your Unit has run? Select all that apply.

See Supplementary Table6for further details.

   

A

Large sample size,e recruiting in several centres, each with multiple treatment providers

Experience in trial type

35

44

80%

 Centre

16

35

46%

 Treatment provider

4

35

11%

 Both

3

35

9%

 Neither

20

35

57%

No experience in trial type

7

44

16%

No response

2

44

5%

B

Small sample size,f With centres each recruiting 2 to 3 patients

Experience in trial type

30

44

68%

 Centre

5

30

17%

 Treatment provider

0

30

0%

 Both

0

30

0%

 Neither

25

30

83%

No experience in trial type

12

44

27%

No response

2

44

5%

C

Recruiting in several centres, where treatment providers treat patients across recruiting centres (treatment provider is not unique to a centre)

Experience in trial type

15

44

34%

 Centre

4

15

27%

 Treatment provider

1

15

7%

 Both

0

15

0%

 Neither

11

15

73%

No experience in trial type

27

44

61%

No response

2

44

5%

D

A trial investigating a surgical intervention, recruiting from several centres, each with multiple treatment providers

Experience in trial type

21

44

48%

 Centre

5

19

24%

 Treatment provider

3

19

14%

 Both

1

19

5%

 Neither

14

19

67%

No experience in trial type

19

44

43%

No response

4

44

9%

E

Recruiting from several centres, each with multiple treatment providers, comparing substantially different interventions, e.g. surgery to an injection

Experience in trial type

14

44

32%

 Centre

5

14

36%

 Treatment provider

1

14

7%

 Both

0

14

0%

 Neither

9

14

64%

No experience in trial type

26

44

59%

No response

4

44

9%

In scenarios where Unit has experience, approaches to stratification changes across scenario, i.e. within-Unit variation to stratification

Different approaches across scenarios

12

44

27%

Same approach across all scenarios

24

44

55%

No response to Question 9

8

44

18%

10

a

If a positive treatment effect is found, does your Unit explore heterogeneity of treatment effects by centre?

See Supplementary Table7for further details.

Yes

32

44

73%

No

9

44

20%

No response

3

44

7%

i. If yes to a, do you explore by graphical display?

Yes

31

32

97%

No

0

32

3%

No response

1

32

3%

ii. If yes to a, do you explore by analytical methods, e.g. significance testing?

Yes

22

32

69%

No

5

32

16%

No response

5

32

16%

b

If a positive treatment effect is found, does your Unit explore heterogeneity of treatment effects by treatment provider?

See Supplementary Table8for further details.

Yes

12

44

27%

No

23

44

52%

No response

9

44

20%

i. If yes to b, do you explore by graphical display?

Yes

11

12

92%

No

0

12

0%

No response

1

12

8%

ii. If yes to b, would you explore by analytical methods, e.g. significance testing?

Yes

9

12

75%

No

1

12

8%

No response

2

12

17%

  1. a’Sometimes’ here is ’usually’—it is a rare exception where we don’t [ID10]
  2. bNo Standard Operating Procedure in place [ID3]
  3. c’Sometimes’ here is ’usually’—it is a rare exception where we don’t [ID10]
  4. dNo experience in trials of this type [ID1]. Not applicable [ID2]
  5. eWith centres each recruiting at least 10 patients
  6. fWith centres each recruiting 2 to 3 patients