clinical trials: easy ways to maximise success and ... · 6/19/2019 · clinical trials: easy ways...

ICTU Workshop (CATO 19 06 2019) 1

Clinical Trials: Easy ways to maximise

success and minimise pain.

CATO Research Symposium

19 June 2019

Workshop Content


• ICTU Introductions

• What are the common pitfalls in clinical

research?

• Discuss examples from 3 ICTU trials

• Concluding remarks

ICTU Introductions


• Daphne Babalis, Operations Manager

• Ana Boshoff, Operations Manager

• Jack Elkes, Clinical Trials Statistician

• Marie Miller, PPI Coordinator

• Claire Smith, Operations & Business

Development Manager

Who are we?


• Imperial Clinical Trials Unit is one

of 46 fully registered UKCRC

CTUs .

• We are interested in supporting

high quality research which

benefits patients.

• We support design, delivery,

analysis and publication of trials

in line with appropriate standards

and regulations.

ICTU

What support can we offer?


What do we support?


Interventional trials

IMPs – all phases ATIMPs

Surgery Medical Devices

Imaging Behavioural Therapies

Observational studies

Diagnostic accuracy and clinical utility studies

Biomarker research

Feasibility trials (likely to lead to a definitive trial)

Trials embedded in Fellowships (usually Post Doc and Senior)

Clinical Audits

Standalone Systematic Reviews (possibly if Evidence Synthesis)

PhD Projects

What are the biggest pitfalls of Clinical Trials?


Audience Response:

Failure to

recruit to

time & target

Complex trial design

Oversight

committees

Visit

schedule

Statistical

assumptions

Align with

Standard

of care

Literature

Randomisation

& blinding

Data

collection

Poor

retention

Performance

monitoring

Deviation

from

protocol

Budget /

resources

Site

selection

Close-out

process

Communication

Stakeholder engagement

Unrealistic eligibility criteria

Detailed protocol

Timelines

No back-

up plan

Set-up

process

Common pitfalls in clinical research

ICTU Workshop (CATO 19 06 2019)

Retention

Communi

cation

Failure to

recruit to

time & target

Unrealistic eligibility criteria

Literature

Align with

Standard

of care

Data

collection

Timelines Poor

retention

Stakeholder engagement

Site

selection

Complex trial design

Oversight

committees

Visit

schedule

Failure to

recruit to time

& target

Statistical

assumptions

Randomisation

& blinding

Performance

monitoring

Deviation

from

protocol

Budget /

resources

Close-out

process

Detailed protocol

No back-

up plan

Set-up

process

Common pitfalls in clinical research



Example One:

Delayed Recruitment


Example 1 – Delayed recruitment

• Patients with Atrial Fibrillation

• 3-arm Randomised Controlled Trial

– Standard care procedure

– Modified standard care procedure (streamlined)

– Drug therapy arm

• Sample size 321 patients

• 10 UK sites

• 13-month recruitment period

• 12-month patient follow-up

11



0

50

100

150

200

250

300

May

Jun

e

July

Au

gust

Septem

ber

Octo

ber

No

vemb

er

Decem

ber

Janu

ary

Febru

ary

March

Ap

ril

May

Jun

e

July

Au

g

Sept

Oct

No

v

Dec

Jan

Feb

Mar

Ap

r

May

Jun

e

July

Au

g

2015 2016 2017

Target Recruitment vs Actual Recruitment

Original cumulative target

Revised cumulative target

Actual recruitment

Example 1 – Recruitment by site (overview)


0

10

20

30

40

50

60

70

80

0 5 10 15 20 25 30

Site target (cumulative)

Site target (total)

Site 1

Site 2

Site 3

Site 4

Site 5

Site 6

Example 1 – Recruitment by site


0

10

20

30

40

50

60

70

80

0 5 10 15 20 25 30


Site target (total)

Site 1

0

10

20

30

40

50

60

70

80

0 5 10 15 20 25 30


Site target (total)

Site 2

Site 4

High recruiter

0

10

20

30

40

50

60

70

80

0 5 10 15 20 25 30


Site target (total)

Site 3

Site 5

Site 6

Low recruiter

On target



• 10 UK sites --> increased to 13 sites

• 13-month recruitment period --> extended to 28 months

• Target recruitment rate 25 pts / month- actual rate 11.5 pts/month

• What would you do differently to avoid this happening again?

– Poor feasibility work

– Unrealistic targets

– Not enough sites / not the best sites

• Lessons

– Planning and feasibility work

– PPI

– Statistical considerations

15


Example Two:

Over Recruitment


• Patients with Septic Shock

• 2-arm Double-blind Randomised Controlled Trial

– Placebo

– Drug therapy

• Sample size 516 patients

• 35 UK sites

• Recruitment period: 18 months

• 24 hour intervention (drug infusion)

• 28 day patient follow-up

Example 2: Over-recruitment

Example 2: Over-recruitment


Recruitment graph

Example two: Over-recruitment


Pros:

• adequate time for final monitoring, data cleaning, data lock, statistical analysis, reports and publications

Cons:

• Sites may struggle to manage the sudden high workload of inputting large amounts of data into the database

• More prone to errors in eligibility/consenting checks

• A higher number of errors in data entry

• In some circumstances recruitment had to be halted in order for staff to be re-trained and data to be kept up to date.

• Increase in monitoring activities and extra staff needed.

Example two: Over-recruitment


• Manage your sites well, have regular contact with them and

provide comprehensive training and support throughout

• Monitor regularly in order to provide a better quality of data.

• Key aspects: Planning and communication!

Creating an excellent relationship with sites meant that they

would call and email with their queries and this in turn led to a

better quality of data being entered.

How to maximise success and minimise pain:


Example Three:

A Recruitment Roller Coaster

Ride


Example 3 – Setting the Scene

• Obese adults with Type 2 Diabetes (at least one year)

• 2-arm open label RCT

– Single use, minimally invasive CE marked device

– Standard Medical Therapy

• Option to consent to mechanistic sub-studies

• Sample size 160 patients (main trial)

• 2 UK hospital sites

• 12-month recruitment period

• 12-month patient follow-up

22


Example 3 – Initial Recruitment Strategy

• 75% via Primary Care

• 25% Other Routes:

•DARE (Diabetes Alliance for Research in England)

•Posters and leaflets in GP surgeries and hospital clinic areas

•Newspaper/Web adverts

•Diabetes and Obesity Support groups

•Study websites (and press release)

•Social media websites (Facebook and Twitter)

•Face to face approach during routine clinic visits

•Secondary care (hospital specialist clinics)

23

Example 3: Target vs. Actual Recruitment

24 ICTU Workshop (CATO 19 06 2019)

Pa

tien

ts

Months

Example 3: Target vs. Actual recruitment (in context)


Pa

tien

ts

Months

Substantial

Amendment

Minor

Amendment

2nd site

opens

1st site

opens

Recruitment issues:

• Poor uptake by NWL GPs.

• Poor patient response to

invitation letters sent by GPs

(< 5%)

Set-up delays:

2nd site opened 6

months late


Example 3 – Meeting with funder

The funder requests a ‘Monitoring Visit’ to discuss

the future of the project.

What options are on the table?

26



• Option 1: Stick to original recruitment timelines

and hope for the best

• Option 2: an extension to the recruitment period

in order to complete recruitment within a fixed

(realistic) time period.

• Option 3: shut the trial

27

Example 3: Recruitment Option 1


Pa

tien

ts

Months

Example 3: Recruitment Option 2


Pa

tien

ts

Months



Which option did the funder agree to?

30

Example 3: Variation on Recruitment Option 2


Pa

tien

ts

Months

Recruit at least 35 patients by

end Dec 2015 then a 6 month

extension will be considered.


Example 3 – Final recruitment outcome

Did the research team achieve their

recruitment target?

32


33

Pa

tie

nts

Months

•ICTU Workshop (CATO 19 06 19)

1 1 8

5

6

11

15

10

14

10

13

9

11

16

13

20 7

Recruited 47pts by

31-Dec-15 so 6M

extension agreed

with funder.


34

Pa

tie

nts

Months


1 1 8

5

6

11

15

10

14

10

13

9

11

16

13

20 7

Recruited 103 patients

by end of 6 month

extension period.

Funder agreed

that recruitment

should continue


35

Pa

tie

nts

Months


1 1 8

5

6

11

15

10

14

10

13

9

11

16

13

20 7

Recruitment

completed

11 months later

than planned.

Example 3: Which methods were most successful?

36

NHS Site 1

(London) NHS Site 2

PATIENTS INTERESTED 1210 601

Source of Patient:

GP

Newspaper Adverts

Study Website

DARE

Other / Unknown

Other Bariatric and Diabetes Clinics

Diabetes UK

Other Research / Science Museum

Poster

Tele Screen Outpatients (Site 1)

Local Radio Interview (Site 2)

Social Media (Facebook or Twitter)

Friend


1004

335

Exercise 3: Lessons Learned


• Allow sufficient time to complete feasibility

• Don’t underestimate how long it takes to set up sites

• Have a recruitment plan A, B, C …

• Don’t assume the same recruitment approach will work for all sites

• Consider running recruitment approaches in parallel. Don’t wait until

one fails in order to try something else.

• Act quickly if something is not working

• Secure sufficient funds for recruitment

• Don’t forget that PPI advice is useful throughout the life cycle of a

project

Concluding remarks


Ways to maximise success and minimise pain:

• Good communication with Stakeholders

• Seek expert advice

• Set realistic timelines & targets

• Robust Feasibility

• Don’t underestimate the Power of PPI

Patient and Public Involvement


Come and visit our stall – marquee on Queen’s

Lawn Sat 29th & Sun 30th

Experience public involvement

14 projects from across Imperial

PPI Training

Interactive training for researchers and patients/members of the

public

Dates for next training season to be scheduled by the end of June

https://www.imperial.ac.uk/patient-experience-research-

centre/ppi/ppi-training/


Thank you for participating.

For more information about ICTU

please visit our website:

https://www.imperial.ac.uk/clinical-trials-unit/

clinical trials: easy ways to maximise success and ... · 6/19/2019 · clinical trials: easy ways...

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