Invigoration through innovation Human Subjects in Clinical Trials Prepared for Involve Conference – People in research Presented by Jane Fiona Cumming

Invigoration through innovation

Human Subjects in Clinical Trials

Prepared for Involve Conference – People in research Presented by Jane Fiona CummingSeptember 2006


Agenda

• Context

• What was put in place

• How members of the public have been involved

• Lessons learnt

• Issues for discussion


Context

This conference

People in researchLooking for practical solutionsPatient centred

This initiative Identifying new sources of riskRisk management“Living” the mission

Our objective today

Focus on and explore key issues indepth


Mirror 1 April 2006THE ELEPHANT MAN EXCLUSIVE: HIS STORYBy Victoria WardTERRIFIED 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.

The press


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


What was put in place

Problem definition stage Is this a risk?

If so, where is it?Is it Roche’s problem?

Next steps

Action planningYes it is a risk

Yes it is partly Roche’s problemThis is what we need

Implementing Evaluating the changes

Pilot in Phase IIIPlanning for wider implementation

Opinion formers, literature review

Participative research groups Including Roche representatives, investigators and subjects

Training for Guidance document Model document Social research

Participative workshop with Roche people

Working with other teams


How was the public involved

Company staff

Groups of investigators and their staff

Groups of patients in hospital

Groups of volunteers at CPU

Patient corridors

Social Research

Putting on other people’s hats Pictures and stories


What was learnt - Risks and opportunities Risks Opportunities

• Lack of standardisation of approach across Investigator sites

• Lack of evidence and transparency as to what sites do

• Inconsistent data

• Early withdrawal of subjects

• Litigation (subject)

• Rejection of trial (regulator / ethics committees)

• Unfavourable publicity

• Focus on the subject (User-friendly)

• Design of ICF & Subject Information documents

• Appending aids e.g. FAQs

• Subject Understanding

• Time to read, Time to ask questions

• Documentation and checking

• Focus on the process

• Ethical

• Minimum standards followed consistently


Objectives: • To increase the transparency of the informed

consent procedure: within Roche, to the investigators and to the subjects.

• To build evidence within Roche.

Lessons learnt - implementation

Implementation:

• Process for Roche staff

• Guidance document

• Model consent form

• Training


“INFORMED CONSENT” STARTS HERE FOR THE

SUBJECT

Process for staff

A. Pre-study contact with subject “Subject recruitment”

B. Initial subject contact with investigator

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.

“INFORMED CONSENT” STARTS HERE FOR ROCHE


What will this approach deliverto 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

subject’s shoes…?

We already have guidelines and SOPs – surely

following those is enough?

Guidance document

Developed guidance document:


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

Weeks 2 and 3

“Model” consent document

A “model” document was created using this guidance and also accredited by the “Plain English” campaign.

Sample flow diagram:


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.

Issues for discussion


For further information contactJane Fiona Cumming

September 2006

Article 13Bradley House26 St Alban’s LaneLondon NW11 7QEwww.article13.comemail: [email protected] 731 7700

Documents

Invigoration through innovation Human Subjects in Clinical Trials Prepared for Involve Conference – People in research Presented by Jane Fiona Cumming