Human Subjects in Clinical Trials

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Human Subjects in Clinical Trials
Prepared for Involve Conference People in
research Presented by Jane Fiona
Cumming September 2006
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Agenda

• Context
• What was put in place
• How members of the public have been involved
• Lessons learnt
• Issues for discussion

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Context
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The press
Mirror 1 April 2006 THE ELEPHANT MAN EXCLUSIVE
HIS STORY By Victoria Ward TERRIFIED Mohamed
Abdelhady lay on his hospital bed awaiting his
drug trial - hideously aware other volunteers
were already writhing in agony. Unknown to him in
minutes he would suffer excruciating pain, his
head would balloon to three times its size and he
would become the original Elephant Man in the
biggest health trial blunder in living
memory. Yet for now he was helpless just waiting
his turn.
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2004 - Risk was informed consent an emerging
issue?

• A number of catastrophes as well, trials going
  wrong
• Needed to be explored
• Reputation of the industry
• Externally, consent and understanding issues
  emerging in the health sector as a whole (Alder
  Hey, Bristol Royal Infirmary)
• Share prices and Corporate governance
• Focuses on risk this lack of understanding of
  informed consent raised internally as a possible
  risk
• Share prices and ratings - of pharma companies
  being affected by behaviour in trials
• Reputation of the company
• Journalist scrutiny
• Employee concern/motivation

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What was put in place
Problem definition stage Is this a risk? If so,
where is it? Is it Roches problem?
? Opinion formers, literature review
? Participative research groups Including
Roche representatives, investigators and
subjects
Action planning Yes it is a risk Yes it is partly
Roches problem This is what we need
? Participative workshop with Roche people
? Training for Guidance document
Model document ? Social research
Implementing Evaluating the changes
Pilot in Phase III Planning for wider
implementation
?Working with other teams
Next steps
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How was the public involved
Company staff
Patient corridors
Social Research
Groups of investigators and their staff
Groups of patients in hospital
Groups of volunteers at CPU
Putting on other peoples hats
Pictures and stories
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What was learnt - Risks and opportunities
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Lessons learnt - implementation

• Objectives
• To increase the transparency of the informed
  consent procedure within Roche, to the
  investigators and to the subjects.
• To build evidence within Roche.

• Implementation
• Process for Roche staff
• Guidance document
• Model consent form
• Training

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Process for staff
INFORMED CONSENT STARTS HERE FOR THE SUBJECT
A. Pre-study contact with subject Subject
recruitment
B. Initial subject contact with investigator
INFORMED CONSENT STARTS HERE FOR ROCHE
C. Written Information Subject Information
leaflet
D. Discussion (Investigator and subject)
E. Time to think/discuss with family etc.
(Balance with local and trial requirements)
Etc.
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Guidance document
Developed guidance document
We already have guidelines and SOPs surely
following those is enough?

• What will this approach deliver
• to me / Roche?
• Better subject understanding can deliver
• Reputation for new and innovative ways of doing
  things
• Lower risk of litigation
• More reliable study data
• Lower risk of subject withdrawal
• Reputation for being an ethical company committed
  to good clinical practice

Put ourselves in the subjects shoes?
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Model consent document
A model document was created using this
guidance and also accredited by the Plain
English campaign.
Sample flow diagram
Weeks 2 and 3

• Week 2
• You will return to the clinic for the appointment
  agreed at your last visit.
• We will take a blood sample to analyse the
  ribavirin in it.
• We will ask you how you are feeling and give you
  a morning dose of ribavirin.
• We will give your first weekly dose of
  peginterferon alfa-2a by injection and make an
  appointment for you to come back in a week.
• Week 3
• You will return for the appointment you made at
  your last visit.
• We will ask you how you are feeling and give you
  a morning dose of ribavirin.

Week 4
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Issues for discussion

• Assumption that the full informed consent
  procedure is carried out consistently by sites.
• The findings in total demonstrate that the focus
  before the initiative was on procedure i.e.
  ensuring IC is in line with current ICH GCP
  guidelines, ensuring that consent is granted
  before the trial, advising subjects on their
  right to withdraw etc.
• However this needs to be widened to include the
  least mentioned part of the IC procedures i.e.
  Ensuring subject understanding and subject safety
  and well being. (Greater Subject Focus).
• The risk for Roche was/is
• Where is the evidence of interaction and checking
  understanding?
• Why is subject safety and well being not a
  salient aspect of IC?
• The evaluation to date demonstrates a useful
  process has been developed to address this.

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For further information contact Jane Fiona Cumming
Article 13 Bradley House 26 St Albans
Lane London NW11 7QE www.article13.com email
janefionac_at_Article13.com 0208 731 7700
September 2006