depression in south yorkshire (depsy) · depression in south yorkshire (depsy) using the ‘cohort...

Depression in South Yorkshire (DEPSY) Using the ‘cohort multiple’ RCT design

to assess treatment by homeopaths for self-reported depression

Petter Viksveen, PhD Student The University of Sheffield

Presentation at the Trials within Cohorts (TwiCs) Symposium

London School of Hygiene & Tropical Medicine 10 – 11 Nov 2014

Supervisors: Dr. Clare Relton, Prof. Jon Nicholl Advisor qualiative study: Prof. Paul Bissell

Depression in South Yorkshire (DEPSY) Using the ‘cohort multiple’ RCT design

to assess treatment by homeopaths for self-reported depression

Aims

To assess the acceptability, the effectiveness, the cost-effectiveness, and the safety of treatment provided by homeopaths for patients with self-reported depression.

To learn from patients’ experiences with treatment provided by homeopaths.

ISRCTN02484593

Viksveen & Relton (2014)

Depression in South Yorkshire (DEPSY) Using the ‘cohort multiple’ RCT design

to assess treatment by homeopaths for self-reported depression

Methods: Pragmatic RCT

Recruitment through the Yorkshire Health Study (YHS)

Screening & baseline data collection: postal questionnaire

Primary outcome: PHQ-9 (6 months), Secondary outcomes: PHQ-9 (12 mo.), GAD-7 (6 & 12 mo.), and EQ-5D (12 mo.)

Intervention: Treatment by homeopaths (9 mo.) + TAU

Control: Treatment as usual (TAU)

Venues: 4 clinics in 4 cities, 7 practitioners

Random selection (1:2 ratio for Offer and No Offer group)

Depression in South Yorkshire (DEPSY) Using the ‘cohort multiple’ RCT design

to assess treatment by homeopaths for self-reported depression

Methods: Qualitative study

Qualitative semi-structured interview study

Offer group patients who received treatment by a homeopath

Interviews at 1-2 and at 6 months, until saturation (max. 30 + 30)

Thematic analysis

Mixed methods (triangulation at interpretation stage)

REC (IRB) experience

REC (IRB) experience

Leeds Central REC:

No questions about or objections to the cmRCT design

Approvals – 23 months

Apr May Feb July Nov 2012 2013 2014

Dec Mar Apr Jul Aug Jan

ISR REC Research Passport

Research Governance

Approval venues

Barnsley Rotherham

Sheffield Doncaster 1 month 3.5 months

4 months

5 months

7 months

Approvals – 23 months

Apr May Feb July Nov 2012 2013 2014

Dec Mar Apr Jul Aug Jan

ISR REC Research Passport

Research Governance

Approval venues

Barnsley Rotherham

Sheffield Doncaster

"[...] the multitude of different application processes that have been implemented mean that research governance presents another large barrier to research." (Torgerson & Dumville 2004, p.710)

1 month 3.5 months 4 months

5 months

7 months

Approvals – 23 months

Apr May Feb July Nov 2012 2013 2014

Dec Mar Apr Jul Aug Jan

ISR REC Research Passport

Research Governance

Approval venues

Barnsley Rotherham

Sheffield Doncaster

Throughout the research governance approval process no objection was made to the use of the cmRCT design.

1 month 3.5 months 4 months

5 months

7 months

Recruitment: Time & financial resources

Recruitment: Time & financial resources

Yorkshire Health Study

22,000 patients consented to be contacted again, of which:

- Long-standing depression: n=1,917 (8.7%)

- Moderately/extremely anxious/depressed: n=3,823 (17.4%)

- LSD or moder./extr. anxious/depressed: n=5,740 (26.1%)

Sent to 5,740 patients

Random selection within 2-3 months

Recruitment: Costs

Recruitment: Costs

5,740 questionnaires: £ 4,200

Recruitment: Costs

5,740 questionnaires: £ 4,200

22,000 questionnaires (est.): £ 13,000

Recruitment: Reaching targets

114 multi-centre trials:

2/3 did not achieve recruitment targets (McDonald et al. 2006)

Recruitment: Reaching targets Numbers of patients in the DEPSY trial, using a "rolling" recruitment procedure (Dec 2013 – Feb 2014):

Sample size calculation Total 484 "No offer" group 323 "Offer" group 162

Recruitment: Reaching targets Numbers of patients in the DEPSY trial, using a "rolling" recruitment procedure (Dec 2013 – Feb 2014):

Sample size calculation Result Total 484 566 (+17%) "No offer" group 323 381 "Offer" group 162 185

Recruitment: Reaching targets Numbers of patients in the DEPSY trial, using a "rolling" recruitment procedure (Dec 2013 – Feb 2014):

Sample size calculation Result Total 484 566 (+17%) "No offer" group 323 381 "Offer" group 162 185 Accepted & treated 75 Not accepted/treated 110

Recruitment: Reaching targets Numbers of patients in the DEPSY trial, using a "rolling" recruitment procedure (Dec 2013 – Feb 2014):

Sample size calculation Result Total 484 566 (+17%) "No offer" group 323 381 "Offer" group 162 185 Accepted & treated 75 Not accepted/treated 110

How will the acceptance rate affect statistical analyses?

Follow-up: response rates & attrition Responders to Mood & Health Questionnaire at 6 months

Random selection 6 month responders Total 566 458 (81%) "No offer" group 381 333 (87%) "Offer" group 185 125 (68%)

Follow-up: response rates & attrition Responders to Mood & Health Questionnaire at 6 months

Random selection 6 month responders Total 566 458 (81%) "No offer" group 381 333 (87%) "Offer" group 185 125 (68%) Treated 75 65 (87%) Not treated 110 60 (55%)

Follow-up: response rates & attrition Responders to Mood & Health Questionnaire at 6 months

Random selection 6 month responders Total 566 458 (81%) "No offer" group 381 333 (87%) "Offer" group 185 125 (68%) Treated 75 65 (87%) Not treated 110 60 (55%)

Follow-up: response rates & attrition Responders to Mood & Health Questionnaire at 6 months

Random selection 6 month responders Total 566 458 (81%) "No offer" group 381 333 (87%) "Offer" group 185 125 (68%) Treated 75 65 (87%) Not treated 110 60 (55%)

Why is there a difference in response rates within the Offer group?

Follow-up: response rates & attrition Responders to Mood & Health Questionnaire at 6 months

Random selection 6 month responders Total 566 458 (81%) "No offer" group 381 333 (87%) "Offer" group 185 125 (68%) Treated 75 65 (87%) Not treated 110 60 (55%)

Why is there a difference in response rates within the Offer group? How do differences in response rates influence analyses?

Follow-up: response rates & attrition Responders to Mood & Health Questionnaire at 6 months

Random selection 6 month responders Total 566 458 (81%) "No offer" group 381 333 (87%) "Offer" group 185 125 (68%) Treated 75 65 (87%) Not treated 110 60 (55%)

Why is there a difference in response rates within the Offer group? How do differences in response rates influence analyses? Can CACE analysis be carried out?

Follow-up: response rates & attrition Responders to Mood & Health Questionnaire at 6 months

Random selection 6 month responders Total 566 458 (81%) "No offer" group 381 333 (87%) "Offer" group 185 125 (68%) Treated 75 65 (87%) Not treated 110 60 (55%)

Why is there a difference in response rates within the Offer group? How do differences in response rates influence analyses? Can CACE analysis be carried out? Do treated and untreated patients in the Offer group differ?

Do baseline values for treated and untreated patients in the Offer group differ?

No significant differences for 16 of 19 baseline characteristics

Do baseline values for treated and untreated patients in the Offer group differ?

No significant differences for 16 of 19 baseline characteristics PHQ-9: Treated 16.30(4.47), Untreated 17.57(4.22), p=0.146

Do baseline values for treated and untreated patients in the Offer group differ?

No significant differences for 16 of 19 baseline characteristics PHQ-9: Treated 16.30(4.47), Untreated 17.57(4.22), p=0.146 - Depr. onset: Treated patients more chronic depression - Past AD use: Treated patients more past AD use Differences could be accounted for by a lower response rate to baseline questions

Do baseline values for treated and untreated patients in the Offer group differ?

No significant differences for 16 of 19 baseline characteristics PHQ-9: Treated 16.30(4.47), Untreated 17.57(4.22), p=0.146 - Depr. onset: Treated patients more chronic depression - Past AD use: Treated patients more past AD use Differences could be accounted for by a lower response rate to baseline questions

- City/Borough: Untreated more from Doncaster, fewer from Barnsley & Sheffield

Pros and cons of using the cmRCT design?

Pros and cons of using the cmRCT design?

Advantages Disadvantages

Ethics = Cohort has approval ?

Pros and cons of using the cmRCT design?

Advantages Disadvantages

Ethics = Cohort has approval ?

Consent ☺ Only from Offer group ?

Pros and cons of using the cmRCT design?

Advantages Disadvantages

Ethics = Cohort has approval ?

Consent ☺ Only from Offer group ?

Recruitment ☺ Higher N? Faster? Refusal of offer

Pros and cons of using the cmRCT design?

Advantages Disadvantages

Ethics = Cohort has approval ?

Consent ☺ Only from Offer group ?

Recruitment ☺ Higher N? Faster? Refusal of offer

Attrition ? No resentful Non-responders among demoralisation untreated in Offer group

Pros and cons of using the cmRCT design?

Advantages Disadvantages

Ethics = Cohort has approval ?

Consent ☺ Only from Offer group ?

Recruitment ☺ Higher N? Faster? Refusal of offer

Attrition ? No resentful Non-responders among demoralisation untreated in Offer group

Costs ☺ $ probably reduced ?

Pros and cons of using the cmRCT design?

Advantages Disadvantages

Ethics = Cohort has approval ?

Consent ☺ Only from Offer group ?

Recruitment ☺ Higher N? Faster? Refusal of offer

Attrition ? No resentful Non-responders among demoralisation untreated in Offer group

Costs ☺ $ probably reduced ?

Generalisability ☺ "Real world" practice ?

Pros and cons of using the cmRCT design?

Advantages Disadvantages

Ethics = Cohort has approval ?

Consent ☺ Only from Offer group ?

Recruitment ☺ Higher N? Faster? Refusal of offer

Attrition ? No resentful Non-responders among demoralisation untreated in Offer group

Costs ☺ $ probably reduced ?

Generalisability ☺ "Real world" practice ?

Aims achieved ? ? ?

References

McDonald AM, Knight RC, Campbell MK, Entwistle VA, Grant AM, Cook JA, Elbourne DR, Francis D, Garcia J, Roberts I, Snowdon C. What influences recruitment to randomised controlled trials? A review of trials funded by two UK funding agencies. Trials 2006; 7:9 doi:10.1186/1745-6215-7-9.

Relton C, Torgerson D, O’Cathain A, Nicholl J. Rethinking pragmatic RCTs: introducing the ‘cohort multiple RCT’ design. BMJ 2010, 340:c1066.

Torgerson DJ, Dumville JC. Ethics review in research. Research governance also delays research. BMJ 2004; 328:710.

Viksveen P, Relton C. Depression treated by homeopaths: a study protocol for a pragmatic cohort multiple randomised controlled trial. Homeopathy 2014; 103:147-152.