Randomising every patient you see:
Software for clinic seat research
Bruce Arroll
Douglas Kingsford
Antonio Fernando III
2010
Department of General Practice & Primary Health Care
Faculty of Medical & Health Science
University of Auckland, Auckland, New Zealand
The problem with RCTs
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Expensive
Exclude many of the patients we see
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May not be the patients we usually see-restrictive
Expensive
Time consuming
Huge amount of paperwork
If paper based need data entry
How generalisable are they
How to get a cheap computer generated
randomisation code to ensure concealed allocation.
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McVickers paper
– Vickers AJ, Scardino PT. The clinically
integrated randomised trial proposed novel
method for conducting large trials at low cost.
Trials (Biomed Central 5/3/2009)
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Integrate RCT in to clinical practice
Randomise every eligible patient
Eligible if clinician uncertain-broad-crucial point
Adverse effects, me too drugs; lifestyle
Patients could enter own data eg adverse effects
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Randomisation “daily”
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20 starter packs of Varenicline (Champix)
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Give them out haphazardly or systematically
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“Pressured” my colleagues to be systematic
Mailed a letter to 40 Maori smokers offering 4 free
visits with or without a starter pack of Champix
4/20 with starter pack replied and 0/20 in control
Conclusion “don’t send out letters to Maori patients”
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Without a starter pack
Better way would be phone call or face to face
Pediatric Oncology-the challenge
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Every child with a malignancy in the (developed
world) is in a randomised controlled trial
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Contributed to increase in survival for leukemia from
about 30% to 90%
Generalisability RCT
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300 patients from 250 GPs
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300 consecutive patients from 3 GPs
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Which has the most generalisability?
Office RCT
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Internet based software
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Make RCTs from office chair simple
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Answer simple research questions as part of every
day clinical work
Ideas for RCT
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Gratitude diaries
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Telephone call from practice nurse
Gratitude diaries
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3 things grateful for and what did to cause them daily
for one week. Control group writes down early life
memories. ? Then once per week
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RCT done with internet sample had an effect up to 6
months later. CES-D 13 vs 10.5
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Once per week enough
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Seligman ME, American psychologist 2005;60;5:410-21
Lyubomirsky S.The How of Happiness: Penguin
No trials in primary care
Anecdote 90%+ patients happy to do them.
Research Question
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Does giving depressed patients a gratitude diary vs
control writing improve their PHQ outcomes at 4 (?)
months
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Inclusion criteria broad
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Any one with PHQ ≥ 10 (600 pts in 4000 patients)
Excl Bipolar; severe drug/alcohol;dementia; personality
disorder; eating disorder; persisting psychotic illness; life
expectancy < 2 years; patient unreliable at attending
appointments
Research Issues
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? Follow up as they come in versus attempt a formal
follow up
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A sample size of 98 patients in each arm will be
required to demonstrate a 2 point reduction on the
PHQ from 13 to 11 with a standard deviation of 5
Issues
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Follow up and analysis
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Stop trial at 4 months and do last value carried forward
Or
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Stop trial at 4 months and take data as found (akin to Kaplan
Meir)
– Analyse using random coefficients which would compare the gradient of
the intervention group and the control group
Develop office based software
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Able to get randomisation code from clinic computer
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Data gets stored on web
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No extra data entry required
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Multiple doctors/nurses can submit data from different
clinics-international collaboration possible
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Privacy assured as each clinic uses own patient file
identifier
Simple entry criteria and simple outcome criteria
Eg 600 patients with PHQ ≥ 10
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Doug Kingsford-sleep deprived
Why PHQ-9 and GAD-7
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Validated in primary care
 In NZ Arroll et al 2010 (not published)
Short
Gives a “diagnosis” categorical
Also continuous score to monitor improvement
Free from June 2010
Currently been used in decision support in our district
health board therefore familiar and used
Data collected after
randomisation-next slide
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Previous psych contact and admissions asked after
randomisation
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Done to simplify recruiting
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Not part of primary outcome
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Used for exploring for future studies
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? Cause any bias
Spectrum
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No gold standard ie post mortem won’t tell you if the
person is depressed.
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Sadness →→→→→→→→→→Depression
↓
Consider Treatment if severe or
persistent
DSM IV
Diagnostic and statistical manual of mental disorders
What is in paper form?
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Consent form –need to be kept/scanned
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Information sheet
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Intervention instructions
Follow up data entry
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Less than 1 minute
PHQ
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9 questions over past month
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Score 10-14 mild major depression
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Score 15-19 moderate major depression
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Score 20+ severe major depression
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Advantage a dichotomous score and a continuous scale
to monitor improvement
PHQ 2009
Total = 19
 Below 10 = 16 people
 10-14 = 1 person
 15-19 = 2 person
 20+ nil
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GAD
Below 8 =14 persons
 8 or more = 5 persons
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Missed consent tick
Analysis
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Both ways
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i.e. all at 4 months –send out/phone for follow up
At 4 months according how they have come in
– Using random coefficients analysis of slopes
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Analyse all
Analyse by PHQ 10-14 and >14
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>14 more difficulty with functioning and may be less able to do Gratitude
diaries
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Start testing July 2010
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Ethics underway
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Beta test in own clinic
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Advice
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Control activity ? 3 memories of past
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Ok to collect data over randomisation
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Follow all at 4 months or as they have come in