Magnus Liungman and Dr Gustaf Edgren present on the lessons learned from developing a healthcare prevention intervention for frequent emergency department visitors.

1. Randomized trials in complex settings:
Lessons learned from developing a healthcare prevention
intervention for frequent emergency department visitors
Nuffield conference: Evaluation of complex care
22 June 2015
Person-centred care and patient activation

2. Who are we?
1
Dr Gustaf Edgren
• MD PhD, Karolinska Institutet
• Associate professor of Epidemiology,
Department of Medical Epidemiology
and Biostatistics, Karolinska Institutet
• Scientific advisor, Health Navigator
Magnus Liungman
• UK Country Manager Health Navigator
• MSc Business Administration, Stockholm
School of Economics
• UCLA Anderson School of Management,
Los Angeles

3. We are presenting work from a 5-year scientific
collaboration
2
5 county councils (regional payors) and
12,000 participating patients in the study
All 15 acute hospitals in the 5 county
councils participate
Health Navigator develops and delivers
the actual intervention program

4. Our main messages today
3
A randomised controlled trial is often the only viable option
to achieve sufficiently strong evidence – especially if you
want to measure effects of interventions
Different RCT variants come with different advantages and
can sometimes provide different answers
With iterative, adaptive designs, randomized trials can be used
to not only develop, but also implement new interventions

5. Starting point was the fact that a small part of population
constitute a large share of the total healthcare cost
4
Note: Example from Stockholm County Council, Sweden. 1 £ = 12,8 SEK (April 2015)
Source: Stockholm County Council, Swedish Bureau of Statistics, Health Navigator analysis
Population
10% of population (200 000 people),
75% of total healthcare cost (30 billion SEK)
1% of the population (20 000 people),
30% of total healthcare cost (12 billion SEK)
Total healthcare cost
(Billion SEK)
2,000,000
0
40
20
30
10
1,000,000500,000 1,500,0000

6. The highest care consuming patient group is dynamic,
which put constraints on possible solutions
5
Increasing frequency
of A&E attendances
Period of non-elective
activity starts, often
repeated admissions
Integrated care package
in place, healthcare
utilisation stabilises
Patient flagged as
high risk patient
Secondary prevention
initiatives initiated
Healthcare cost
per patient
Time
OUR AMBITION
Up to 1 year, often less

7. Our aim was to develop a new effective case management
intervention for frequent emergency department visitors
6

8. The implementation of the intervention had a high
degree of uncertainty on approach and target group
7

9. Given the uncertainty we needed an effective evaluation
method and RCT was identified as most attractive option
8
Matched control
Historical controls
RCT
Uncontrolled trial
Options for study design
• Regression to the mean
• High risk of residual confounding

10. We worked with two different RCT models to ensure our
results
9
All patients
Target group
Invited patients
Participants
Excluded
Control
“Non-participants”
No
RCT, Zelen’s design
Intervention group: ”Intention to Treat”
No
Yes
Yes
Meets selection criteria?
Randomisation
No
Wants to participate?
Yes
All patients
Invited
Target group
Intervention
Excluded
“Nay-sayers”
Control
No
Intervention group
No
Yes
Yes
Meets selection criteria?
No
Wants to participate?
Yes
“Traditional” RCT
Randomisation

11. The RCT variants came with different advantages
10
• Zelen’s design is cheaper
• Mimics real-life
• Possible to ’sell’ as not
research
• Better statistical power
• Provides estimates of efficacy
• Less sensitive to non-
participation
RCT, Zelen’s design “Traditional” RCT
+
_ • More expensive
• Takes more time to get
patients into the intervention
• Ethical aspects?
• May underestimate
effects of the intervention
• Ethical aspects?

12. We used an adaptive approach during the study
11
Traditional approach Adaptive approach
VS

13. The protocol was iteratively improved through the use of
interim analysis
12
Frequent interim
analyses
Assessing effect of
intervention
New knowledge
Improved opportunities
to ensure efficient and
working intervention
Modification
Gradually modification
and standardization of
the intervention model
Delivery of
intervention
According to current
protocol

14. The RCT methodology proved critical for the successful
iteration and development of the intervention
13
-10
-5
0
5
10
15
20
25
30
2010 2011 2012 2013
Reduction in total
healthcare cost (%)
• Improved selection
• Improved training
• Better support for
intervention delivery
• Standardisation
• Better selection
and prediction
• Experienced nurses
• New intervention
• High enthusiasm
• Small number of
patients
• Scale-up
• Untrained nurses

15. Today, five years later…
14
• The case management intervention is permanently
implemented in Stockholm
• Reducing A&E admissions with 2-4% on system-wide level
• Readmissions within 30 days have declined with 15-20%
• Based on the results achieved in Sweden, Denmark has
taken a national decision to implement the intervention
• It will be implemented as a huge RCT that starts now and
will go on at least until 2018
• In UK we are now starting up RCTs to test and improve the
interventions in several CCGs

16. To summarize…
15
A randomised controlled trial is often the only viable option
to achieve sufficiently strong evidence – especially if you
want to measure effects of interventions
Different RCT variants come with different advantages and
can sometimes provide different answers
With iterative, adaptive designs, randomized trials can be used
to not only develop but also implement new interventions