Introduction
Motor neuron disease
Trials in MND
Recruitment and retention
Aims
Hypothesis
Materials and methods
Study assessments
Analysis plan
Results
Participant overview
Characteristics | Study participants (N = 120) | Consent to Share clinical data for research provided on CARE–MND register (N = 295) | Consent to be contact about research studies provided on CARE–MND register (N = 216) |
---|---|---|---|
Age at participation in years, mean (SD) | 66 (9) | N/A | N/A |
Age at diagnosis in years, mean (SD) | 62 (10) | 61 (14) | 60 (14) |
Survival length (%) | |||
Long survivors (> 7 years) | 17 (14) | 55 (19) | 39 (18) |
Males, no. (%) | 81 (68) | 172 (58) | 136 (63) |
MND sub-type, no. (%) | |||
ALS | 73 (60) | 193 (65) | 135 (63) |
PLS | 16 (13) | 31 (11) | 25 (12) |
PBP | 15 (12) | 25 (8) | 18 (8) |
PMA | 5 (4) | 10 (3) | 9 (4) |
Other | 3 (3) | 11 (4) | 8 (3) |
No data | 8 (8) | 25 (9) | 21 (10) |
Bulbar onset (%) | 28 (23) | 89 (30) | 61 (28) |
Intervention use (%) | |||
Riluzole | 39 (33) | 91 (31) | 74 (34) |
Non-invasive ventilation | 12 (10) | 47 (16) | 40 (19) |
Gastrostomy | 19 (16) | 67 (23) | 45 (21) |
Attitudes to trials questionnaire
Mean score, interpretation (n) | |
---|---|
Barriers to participationc | |
(2) The distance to the clinic is too far | 3.2, Slightly important (118) |
(1) The time commitment required to participate | 2.9, Slightly important (118) |
(6) I am concerned about the potential dangers and side effects of trial medicationsb | 2.9, Slightly important (119) |
(7) I am worried about the possibility of being assigned to the placebo groupb | 2.7, Slightly important (117) |
(3) I would not feel well enough to participate because of how my condition affects me | 2.6, Slightly important (119) |
(5) I may not benefit personally from the development of new drugs | 2.4, Not at all (117) |
(4) I am already participating in other research projects | 2.3, Not at all (116) |
(8) I already feel I have a lot of appointments | 2.2, Not at all (118) |
Reasons for participationc | |
(12) I want to help other people with the same condition as me | 4.8, Very important (118) |
(14) I want the opportunity to contribute to research | 4.6, Very important (119) |
(9) I may get to try new medicines which are not available to everyone with my condition | 4.1, Quite important (119) |
(10) I will get additional monitoring of how my condition is changing | 3.9, Quite important (119) |
(11) I will receive more regular contact with medical staff | 3.7, Quite important (118) |
(13) I have participated in research before and had a positive experienceb | 2.4, Slightly important (116) |
Understanding of clinical trials and multi-arm multi-stage designa | |
(15) Why clinical trials often need to have a group of people taking a placebo drug | 4.0, Good understanding (119) |
(16) Why not everyone may be suitable to participate in a specific clinical trial | 4.0, Good understanding (118) |
(17) Why researchers believe these experimental treatments may be effective | 3.9, Good understanding (119) |
(19) Why having multiple ‘arms’ means we can test more than one drug and why this matters | 3.5, Some understanding, (119) |
(18) What is a re-purposed medicine and why may it be effective in my condition | 3.4, Some understanding (119) |
Overview of recruitment and retention
Interest in participation shown | Remaining in MND–SMART participants | MND–SMART participants | No engagement | |
---|---|---|---|---|
Registered interest with the trial team, were screened for participation or joined MND–SMART | Participated in MND–SMART and remain participants at 1-year timepoint | Participated in MND–SMART at some stage in the 1-year time frame | Did not become MND–SMART participants and did not register interest | |
n = 93 | n = 38 | n = 59 | n = 48 | |
Gender | ||||
Male | 63 | 25 | 41 | 31 |
Female | 30 | 13 | 18 | 17 |
Long survivor | ||||
Yes | 19 | 10 | 11 | 15 |
No | 74 | 28 | 48 | 33 |
Region of onset | ||||
Lower limb | 37 | 20 | 25 | 16 |
Upper limb | 21 | 10 | 14 | 9 |
Bulbar | 18 | 5 | 13 | 16 |
Respiratory | 2 | 2 | 2 | - |
Mixed | 9 | 1 | 3 | 5 |
No data | 6 | – | 2 | 2 |
Sub-type | ||||
ALS | 59 | 24 | 36 | 33 |
PLS | 14 | 8 | 9 | 5 |
PMA | 3 | 2 | 2 | 2 |
PBP | 9 | 2 | 8 | 6 |
MND–FTD | 1 | – | – | 1 |
Other | 2 | 1 | 2 | – |
Mean (SD) | ||||
---|---|---|---|---|
Age | 64.91 (9.01) | 62.66 (10.29) | 63.53 (9.35) | 70 (7.98) |
Number of interventions used | 0.56 (0.63) | 0.53 (0.60) | 0.63 (0.64) | 0.65 (0.73) |
Number of studies previously participated in | 0.91 (1.39) | 1.13 (1.38) | 1.02 (1.47) | 1.02 (1.45) |
ECAS total score | 109.73 (13.32) | 108.97 (12.85) | 109.48 (13.23) | 116.17 (10.74) |
ALSFRS (R) | 32.99 (8.87) | 34.58 (7.63) | 32.72 (9.02) | 30.53 (9.59) |
HADS | ||||
Anxiety | 5.99 (3.91) | 5.79 (4.13) | 6.31 (4.20) | 5.58 (4.01) |
Depression | 6.16 (3.56) | 5.32 (3.29) | 6.00 (3.62) | 6.92 (3.04) |
Total | 12.44 (6.85) | 11.34 (7.14) | 12.56 (7.31) | 12.71 (6.53) |
STAI | ||||
State | 45.84 (5.54) | 46.50 (5.34) | 45.92 (5.73) | 45.44 (6.25) |
Trait | 45.24 (5.22) | 45.76 (5.13) | 45.25 (5.30) | 43.65 (6.68) |
Total | 90.87 (9.44) | 92.05 (8.92) | 91.03 (9.62) | 88.65 (11.05) |
PHQ | ||||
Total | 6.86 (5.29) | 6.89 (4.14) | 7.02 (4.55) | 7.17 (6.03) |
Presence of suicidality n (%) | 18 (19) | 4 (11) | 11 (19) | 11 (23) |
ALSQOL | 4.80 (1.39) | 4.74 (1.46) | 4.98 (1.39) | 4.96 (1.41) |
HRQOL | ||||
Overall health | 2.86 (1.12) | 2.95 (1.06) | 2.93 (1.08) | 2.46 (1.07) |
Physical health symptoms | 13.87 (12.86) | 14.76 (12.79) | 13.14 (12.70) | 18.62 (13.15) |
Mental health symptoms | 7.17 (9.49) | 9.38 (11.16) | 8.60 (10.42) | 5.48 (7.82) |
Days impacting usual activities | 9.24 (12.25) | 10.03 (12.57) | 10.28 (12.89) | 10.75 (12.71) |
bDAS | 7.82 (5.27) | 6.26 (4.70) | 6.77 (4.89) | 8.45 (5.21) |
Variables associated with recruitment to MND–SMART
Estimate | OR | 95% CI | z | df | p value | |
---|---|---|---|---|---|---|
Recruitment | ||||||
Intercept | ||||||
Number of studies | − 0.57 | − 0.26 | 117 | 0.81 | ||
Previously participated in | 0.04 | 1.04 | 0.80–1.35 | 0.32 | 0.75 | |
Intercept | 5.46 | 3.45 | 117 | 0.0006** | ||
Age at participation | − 0.08 | 0.92 | 0.88–0.96 | − 3.49 | 0.0005** | |
Intercept | − 0.12 | − 0.49 | 117 | 0.63 | ||
Number of interventions | 0.17 | 1.19 | 0.69–2.06 | 0.63 | 0.53 | |
Intercept | 3.90 | 1.41 | 65 | 0.16 | ||
ECAS | − 0.02 | 0.98 | 0.93–1.02 | − 0.97 | 0.33 | |
Intercept | − 0.122 | − 0.17 | 105 | 0.86 | ||
ALSFRS(R) | 0.009 | 1.01 | 0.97–1.05 | 0.42 | 0.67 | |
Intercept | 117 | |||||
HADS total | − 0.15 | 1.01 | 0.96–1.06 | − 0.04 | 0.69 | |
HADS anxiety | 0.01 | 1.06 | 0.97–1.17 | 0.40 | 0.68 | |
HADS depression | 0.06 | 0.96 | 0.87–1.07 | 1.32 | 0.18 | |
Intercept | − 1.10 | − 0.68 | 117 | 0.50 | ||
STAI total | 0.01 | 1.01 | 0.98–1.05 | 0.67 | 0.50 | |
STAI state | 0.001 | 1.001 | 0.94–1.06 | 0.03 | 0.98 | |
STAI trait | 0.03 | 1.03 | 0.97–1.10 | 0.94 | 0.35 | |
Intercept | − 0.16 | − 0.52 | 117 | 0.60 | ||
PHQ total | 0.02 | 1.02 | 0.95–1.10 | 0.58 | 0.56 | |
Intercept | − 0.54 | − 0.84 | 117 | 0.40 | ||
ALSQOL | 0.11 | 1.12 | 0.88–1.45 | 0.84 | 0.40 | |
Intercept | 0.69 | 1.67 | 84 | 0.11 | ||
bDAS | − 0.08 | 0.92 | 0.84–1.00 | − 1.82 | 0.07 | |
Retention | ||||||
Intercept | ||||||
Number of studies | 0.87 | − 3.60 | 0.0003*** | |||
Previously participated in | 0.11 | 1.11 | 0.85–1.45 | 0.82 | 117 | 0.41 |
Intercept | 4.13 | 2.62 | 0.009** | |||
Age at participation | − 0.07 | 0.93 | 0.88–0.97 | − 3.09 | 117 | 0.002** |
Intercept | − 0.64 | − 2.47 | 117 | 0.01* | ||
Number of interventions | − 0.21 | 0.81 | 0.44–1.45 | − 0.69 | 0.49 | |
Intercept | 2.17 | 1.01 | 0.31 | |||
ECAS | 0.02 | 0.98 | 0.94–1.02 | − 0.92 | 65 | 0.36 |
Intercept | − 2.05 | − 2.50 | 0.01* | |||
ALSFRS(R) | 0.04 | 1.05 | 1.01–1.10 | 1.82 | 105 | 0.07 |
Intercept | -0.37 | − 0.91 | 117 | 0.36 | ||
HADS total | − 0.03 | 0.97 | 0.90–1.03 | − 1.05 | 0.29 | |
HADS anxiety | − 0.002 | 1.10 | 0.90–1.09 | − 0.05 | 0.96 | |
HADS depression | − 0.12 | 0.89 | 0.78–1.10 | − 1.93 | 0.05 | |
Intercept | − 2.9 | − 1.59 | 117 | 0.11 | ||
STAI total | 0.02 | 1.02 | 0.99–1.07 | 1.19 | 0.23 | |
STAI state | 0.03 | 1.03 | 0.96–1.10 | 0.76 | 0.45 | |
STAI trait | 0.04 | 1.05 | 0.98–1.12 | 1.28 | 0.20 | |
Intercept | − 0.81 | − 2.51 | 117 | 0.01* | ||
PHQ total | 0.009 | 1.01 | 0.93–1.09 | 0.23 | 0.82 | |
Intercept | − 0.35 | − 0.51 | 117 | 0.61 | ||
ALSQOL | − 0.08 | 0.92 | 0.70–1.20 | − 0.61 | 0.54 | |
Intercept | 0.19 | 0.45 | 0.65 | |||
bDAS | − 0.10 | 0.90 | 0.81–0.99 | − 2.01 | 84 | 0.04* |
N | X2 | df | p value | |
---|---|---|---|---|
Recruitment | ||||
Gender | 119 | 0.02 | 1 | 0.89 |
Long survivor | 119 | 0.68 | 1 | 0.41 |
Region of onset | 112 | 7.81 | 5 | 0.17 |
Disease subtype | 115 | 4.76 | 6 | 0.57 |
Caregiver co-participating | 119 | 0.12 | 1 | 0.72 |
PHQ suicidality presence | 119 | 5.2 | 1 | 1.00 |
Retention | ||||
Gender | 119 | 0.03 | 1 | 0.88 |
Long survivor | 119 | 0.17 | 1 | 0.68 |
Region of onset | 112 | 17.79 | 5 | 0.003** |
Disease subtype | 115 | 6.52 | 6 | 0.37 |
Caregiver Co-participating | 119 | 1.78 | 1 | 0.18 |
PHQ suicidality presence | 119 | 1.64 | 1 | 0.2 |