Background
NMA using individual patient data
NMA using time to event related outcome data
Developing a NMA combining AD and IPD data to synthesise time to event related outcomes
Motivating example: high compression treatments for venous leg ulcers
ID | Study | Treatment | Follow up (weeks) | Number patients | Mean duration (months) | Mean size (cm2) | Number healed | Evidence format available |
---|---|---|---|---|---|---|---|---|
16 | Duby et al. 1993 [18] | 4LB | 12 | 25 | 20.5 | 11.9 | 11 | AD |
SSB | 12 | 25 | 26.7 | 13.1 | 10 | |||
17 | Scriven et al. 1998 [19] | 4LB | 52 | 32 | 13 | 13.3 | 17.6 | AD |
SSB | 52 | 32 | 21 | 8.3 | 18.24 | |||
18 | Partsch et al. 2001 [20] | 4LB | 16 | 53 | 1.25 | 1.5 | 33 | AD |
SSB | 16 | 59 | 1 | 1.9 | 43 | |||
19 | Ukat et al. 2003 [21] | 4LB | 12 | 44 | -- | 17.7 | 13 | AD |
SSB | 12 | 45 | -- | 12.2 | 10 | |||
20 | Franks et al. 2004 [22] | 4LB | 24 | 74 | 2 | 5 | 59 | AD |
SSB | 24 | 82 | 2 | 3.5 | 62 | |||
21 | Junger et al. 2004b [23] | SSB | 12 | 60 | 5.57 | 5.95 | 19 | AD |
HH | 12 | 61 | 4.14 | 5.62 | 29 | |||
22 | Kralj et al. 1996 [24] | 4LB | 24 | 20 | 7.9 | 18.6 | 7 | AD |
Ad hoc: Ba | 24 | 20 | 6.9 | 17.2 | 8 | |||
23 | Polignano et al. 2004b [25] | 4LB | 24 | 39 | -- | 10.1 | 29 | AD |
ZINC | 24 | 29 | -- | 9.3 | 19 | |||
24 | Wilkinson et al. 1997 [26] | 4LB | 12 | 17 | -- | 11.2 | 8 | AD |
Ad hoc: BHeH | 12 | 18 | -- | 8.6 | 8 | |||
25 | Colgan et al. 1995 [27] | 4LB | 12 | 10 | 9.3 | 27.5 | 6 | AD |
Ad hoc: BzeaH | 12 | 10 | 66.5 | 48.5 | 7 | |||
26 | Blecken et al. 2005 [28] | 4LB | 12 | 12 | -- | 50.08 | 4 | AD |
Ad hoc: HV | 12 | 12 | -- | 48.98 | 4 | |||
27 | Moffatt et al. 2008 [29] | 4LB | 4 | 42 | 48.8 | 5.7 | 3 | AD |
2LB | 4 | 39 | 46.6 | 11.8 | 6 | |||
28 | Szewczyk et al. 2010 [30] | 4LB | 12 | 15 | -- | 6 | 9 | AD |
2LB | 12 | 16 | -- | 5.3 | 10 | |||
29 | Wong et al. 2012 [31] | 4LB | 24 | 107 | -- | -- | 72 | AD |
SSB | 24 | 107 | -- | -- | 77 | |||
30 | Iglesias et al. 2004 [32] | 4LB | 52 | 195 | 3 | 3.81 | 107 | IPD |
SSB | 52 | 192 | 3 | 3.82 | 86 | |||
14 | Ashby et al. 2013 [17] | 4LB | 52 | 224 | 12.29 | 9.30 | 157 | IPD |
HH | 52 | 230 | 10.82 | 9.41 | 163 |
Methods
Statistical model for the data
Alternative modelling assumptions
Exploring between-study variation
Time to healing distributions
Distributional shape parameter
Treatment-covariate associations
Model selection and implementation
Results
Model A
|
Model B
|
Model C1
|
Model C2
|
Model D
| ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Hazard ratios | HR | Median (95% CrI) | P | HR | Median (95% CrI) | P | HR | Median (95% CrI) | P | HR | Median (95% CrI) | P | HR | Median (95% CrI) | P | |
Treatment effects
|
4LB
| — | — | 5.5 | — | — | 1.4 | — | — | 6.2 | — | — | 5.7 | — | — | 4.3 |
SSB
| 0.88 | (0.76, 1.03) | 0.4 | 0.96 | (0.77, 1.22) | 0.6 | 0.89 | (0.77, 1.04) | 0.6 | 0.89 | (0.77, 1.04) | 0.6 | 0.84 | (0.70, 0.99) | 0.2 | |
HH
| 1.05 | (0.85, 1.29) | 16.1 | 1.63 | (0.76, 3.53) | 59.2 | 1.03 | (0.83, 1.27) | 14.9 | 1.03 | (0.84, 1.27) | 15.0 | 1.03 | (0.84, 1.28) | 11.1 | |
ZINC
| 0.77 | (0.41, 1.42) | 6.2 | 0.78 | (0.37, 1.62) | 2.8 | 0.78 | (0.41, 1.44) | 6.5 | 0.78 | (0.41, 1.43) | 6.7 | 0.75 | (0.03, 29.49) | 17.5 | |
2LB
| 1.40 | (0.65, 3.05) | 71.9 | 1.39 | (0.62, 3.30) | 36.0 | 1.38 | (0.66, 3.05) | 71.8 | 1.38 | (0.63, 3.04) | 72.0 | 1.59 | (0.61, 5.34) | 67.0 | |
Baseline characteristics
|
Log area
| 0.71 | (0.66, 0.76) | — | 0.71 | (0.66, 0.76) | — | 0.70 | (0.65, 0.75) | — | 0.70 | (0.65, 0.75) | — | 0.71 | (0.65, 0.76) | — |
Log duration
| 0.92 | (0.90, 0.94) | — | 0.92 | (0.90, 0.94) | — | 0.92 | (0.91, 0.94) | — | 0.93 | (0.91, 0.94) | — | 0.92 | (0.90, 0.94) | — | |
Difficulty in walking
| 0.71 | (0.60, 0.85) | — | 0.73 | (0.60, 0.86) | — | 0.72 | (0.60, 0.85) | — | 0.72 | (0.60, 0.85) | — | 0.71 | (0.60, 0.80) | — | |
Immobile
| 0.67 | (0.23, 1.52) | — | 0.66 | (0.23, 1.51) | — | 0.72 | (0.24, 1.65) | — | 0.72 | (0.25, 1.67) | — | 0.68 | (0.24, 1.59) | — | |
Interactions
|
Log area
| — | — | — | — | — | — | — | — | — | — | — | — | 1.00 | (0.97, 1.10) | — |
Log duration
| — | — | — | — | — | — | — | — | — | — | — | — | 1.00 | (0.99, 1.00) | — | |
Btw-centre SD
| 0.04 | (0.01, 0.13) | — | 0.05 | (0.01, 0.13) | — | 0.05 | (0.01, 0.15) | — | 0.05 | (0.01, 0.15) | — | — | |||
Btw-study SD
| — | — | — | 0.13 | (0.01, 0.51) | — | — | — | — | — | — | — | — | — | — | |
λ
| 1.07 | (1.01, 1.13) | — | 1.07 | (1.01, 1.14) |
λ
1
**
| 0.93 | (0.86, 1.01) |
λ
1
| 0.93 | (0.86, 1.01) | — | 1.07 | (1.01, 1.14) | — | |
λ
2
| 1.27 | (1.17, 1.38) |
λ
2
**
| 1.27 | (1.17, 1.38) | |||||||||||
DIC
| 5396.2 | 5396.2 | 5371.2 | 5371.5 | 5377.4 |
Exploring between-study variation
Time to healing distributions
Time to event model
| Akaike Information Criteria (AIC) | |
---|---|---|
IPD study 1 (30) | IPD study 2 (14) | |
Weibull PH
| 1102.1 | 1021.0 |
Gompertz PH
| 1072.5 | 1065.5 |
Exponential PH
| 1102.7 | 1068.4 |
Log-Logistic AFT
| 1026.1 | 971.8 |
Log-Normal AFT
| 1032.2 | 961.5 |