The PACE Trial

Julia DeCesare
Trial Manager
PACE Trial Coordinating Centre (PTCC)
Queen Mary University of London

The PACE Trial

The challenges of setting up the PACE trial

from a Trial Managers perspective in the
current regulatory climate

The PACE Trial

Short title of trial:
Pacing, graded Activity, and Cognitive behaviour therapy; a
randomised Evaluation

Long title of trial:

A randomised controlled trial of adaptive pacing, cognitive
behaviour therapy, and graded exercise, as supplements
to standardised specialist medical care versus
standardised specialist medical care alone for patients
with the chronic fatigue syndrome / myalgic
encephalomyelitis or encephalopathy

Trial design
600 patients in 6 UK
secondary care
specialist chronic fatigue clinics

SSMC Alone

12 months
follow-up

APT + SSMC

CBT + SSMC

GET + SSMC

12 months
follow-up

12 months
follow-up

12 months
follow-up

1. The challenges
Ethics approval
First approved: 31 March 2003
Final approval: 02 February 2005
Caught between two systems
Process of piloting therapies
Volume of trial materials
Disease poorly understood

2. The challenges
Staff recruitment
Shortage of therapists
AfC and manualised therapies
Retention of staff (unusual career path)
Compliance with manuals
Therapy is not as easy to administer as a
drug supply!

2. The challenges
Freedom of information Act
Controversy of trial
Enquiries for sensitive documentation
Clinical trial but not a drug trial
Working within guidelines that dont
always apply

3. The challenges
Participant compliance
Large number of visits for a fatigued
population
5 research visits
15 therapy sessions
3 (minimum) sessions with a doctor

Harder to judge compliance

with therapy
completion of homework (no pills to count!)

4. The challenges
Measurement load
Poorly understood syndrome
Multiple possible contributing factors
Perceptual process
= Many, many measurements, thousands of
Case Report Forms and an enormous
quantity of data points to check!

1. The Advantages
No drugs!

No QP
No labelling
No drug accountability
No pharmacy contracts or audits
SUSARs and side effects unlikely

No MHRA registration
No fees
Less likelihood of inspection
No EUDRACT database reporting

Always new and interesting!

Pacing, graded Activity, and Cognitive

behaviour therapy; a randomised
Evaluation

The PACE Trial

Julia DeCesare
Trial Manager
PACE Trial Coordinating Centre (PTCC)
Queen Mary University of London

My name is Julia DeCesare and I am the Trial Manager for the PACE trial. A
multi-centre randomised clinical trial for CFS/ME funded by the MRC, DH,
DWP and Scottish Executive.
CLICK

The PACE Trial

The challenges of setting up the PACE trial

from a Trial Managers perspective in the
current regulatory climate

I am going to talk to you about the challenges of running the PACE clinical trial
from my perspective as the trial manager, in the current regulatory climate.

The PACE Trial

Short title of trial:
Pacing, graded Activity, and Cognitive behaviour therapy; a
randomised Evaluation

Long title of trial:

A randomised controlled trial of adaptive pacing, cognitive
behaviour therapy, and graded exercise, as supplements
to standardised specialist medical care versus
standardised specialist medical care alone for patients
with the chronic fatigue syndrome / myalgic
encephalomyelitis or encephalopathy

The PACE acronym is derived as you see here. This is a randomised

controlled clinical trial for patients with CFS/ME employing all non-drug
therapies.
This is the most ambitious trial for CFS/ME that has ever been attempted with
no previous trial aiming to recruit such a large number of participants.

Trial design
600 patients in 6 UK
secondary care
specialist chronic fatigue clinics

SSMC Alone

12 months
follow-up

APT + SSMC

CBT + SSMC

GET + SSMC

12 months
follow-up

12 months
follow-up

12 months
follow-up

-There are six specialist secondary care CFS services in the UK involved in
the PACE trial: including Edinburgh, Oxford and four London centres
including two here at Barts. The CFS services are themselves each unique
with some being based in infectious Disease clinics and others in
psychological medicine.
-As you can see this is a four arm trial. All participants receive Standardised
Specialist Medical Care (SSMC) and they are randomised to either receive
only this specialist advice, or to also have a therapy which might be Adaptive
Pacing Therapy (principally given by occupational therapists) or Cognitive
Behaviour Therapy (usually delivered by a psychologist or CBT nurse
specialist) or Graded Exercise Therapy (which is normally given by a
physiotherapist or exercise physiologist).
-All participants are followed up over the course of 12 months.
- As you can see from this, all the treatments in PACE are non-drug so initially
when I joined PACE, I had, perhaps naively, thought that this might be a
simpler clinical trial to run as there were no medicinal products or associated
regulations to be concerned about.

1. The challenges
Ethics approval
First approved: 31 March 2003
Final approval: 02 February 2005
Caught between two systems
Process of piloting therapies
Volume of trial materials
Disease poorly understood

The reality is that even without drugs to worry about, PACE has been a
complex study to implement and I am going to talk briefly though some of the
main challenges.
(Talk to slide, the trial was first approved in 2003 and after a period of
recruiting staff, piloting the therapies and local centre set up, the trial was
finally ready to open to recruitment, six months late, in March of this year. One
of the greater hold ups to starting was attaining this final ethical approval.)
Change over of REC system biggest problem.
Working between different sets of forms.
Timelines are different.
Changes could not be minor in the initial stages.
No longer Chairmans action so there is often no single easy contact in a REC
to communicate with, administrators very stressed.

2. The challenges
Staff recruitment
Shortage of therapists
AfC and manualised therapies
Retention of staff (unusual career path)
Compliance with manuals
Therapy is not as easy to administer as a
drug supply!

2. The challenges
Freedom of information Act
Controversy of trial
Enquiries for sensitive documentation
Clinical trial but not a drug trial
Working within guidelines that dont
always apply

3. The challenges
Participant compliance
Large number of visits for a fatigued
population
5 research visits
15 therapy sessions
3 (minimum) sessions with a doctor

Harder to judge compliance

with therapy
completion of homework (no pills to count!)

4. The challenges
Measurement load
Poorly understood syndrome
Multiple possible contributing factors
Perceptual process
= Many, many measurements, thousands of
Case Report Forms and an enormous
quantity of data points to check!

1. The Advantages
No drugs!

No QP
No labelling
No drug accountability
No pharmacy contracts or audits
SUSARs and side effects unlikely

No MHRA registration
No fees
Less likelihood of inspection
No EUDRACT database reporting

Always new and interesting!

But so as not to be entirely negative, there are some definite advantages.

The major advantage is that there is no drug supply to worry about.

Dealing with therapists rather than a drug supply makes this trial far more
interactive on a day to day basis. At this stage, many trials are settling into a
pattern and there is little to do than watch the data come in. On PACE there
are always new challenges and new ideas generated by the fat that the team
is necessarily very interactive.

Pacing, graded Activity, and Cognitive

behaviour therapy; a randomised
Evaluation

The PACE acronym is derived as you see here. This is a randomised

controlled clinical trial for patients with CFS/ME employing all non-drug
therapies.
This is the most ambitious trial for CFS/ME that has ever been attempted with
no previous trial aiming to recruit such a large number of participants.