Clinical Trials: Ethical Issues and Seeking Informed Consent

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Clinical TrialsEthical Issues and Seeking
Informed Consent
Dr Nadia Harbeck Dept. of Obstetrics and
Gynaecology, Technical University of Munich,
Germany
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What are clinical trials?

• Carefully controlled research studies that are
  conducted in human volunteers, to determine
  whether new drugs or treatments are safe and
  effective
• This research plays a vital part in the
  development of new methods
• of treatment and care

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Why are clinical trials needed?

• Despite recent advances the need remains for
  better ways of preventing, diagnosing and
  treating cancer
• Clinical trials aim to
• Find out how well new treatments work
• Find therapy strategies for individual
• patients
• Identify new ways to provide help and
• support for patients

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How is a new anti-cancer drug tested in patients?

• Phase I
• Is it safe?
• Phase II
• Does it work?
• Phase III
• Is it more effective than current treatments?

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Phase III trial Bondronat in the treatment of
bone pain
RANDO MIS ATION
Bondronat
Patients with cancer related bone pain
Best existing treatment
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Development of a new breast cancer drug

• Herceptin (trastuzumab)
• First approved biological therapy in breast
  cancer

1993
1997
1994
1995
1996
1992
1998
1985
1991
1990
Phase III
Phase II
Phase I for human antibody
FDA approval
Cloning of target (HER2)
Mouse antibody
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Types of clinical trials

• Prevention
• Diagnostic
• Screening
• Treatment
• Early disease (no visible spread)
• Advanced disease (disease has spread)

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Screening trial to assess the need for
chemotherapy
Non-agressive tumour
Observation
Node-negative Breast Cancer
TISSUE TESTING
Chemotherapy
Agressive tumour
RANDOMISATION
Observation
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Some patients can be spared chemotherapy
100
70
30
50
0
not cured
Intermediate risk
cured
Natural course of disease
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Design of clinical trials

• Randomised trials
• Ensure that no systematic difference between
  subjects occurs, allowing valid analysis of
  results
• However, not always appropriate in cancer trials..

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Xeloda versus paclitaxel difficulties with
randomisation
RANDO MIS ATION
Xeloda
Patients with metastatic breast cancer
Target Number not Reached patients strongly
preferred established i.v. therapy or novel, oral
agent and therefore refused randomisation to
study treatment
Paclitaxel
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Design of clinical trials

• Blinding
• Necessary to avoid bias and improve the accuracy
  of study results
• Single blinded only study participants blinded
• Double blinded study participants and
  investigators blinded

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Design of clinical trials

• Placebo-controlled trials
• Compare a treatments effectiveness with a
  placebo (dummy treatment)
• The participants in the control group will
  receive a placebo instead of an active drug

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Placebo and cancer trials

• Placebo not always an appropriate comparator in
  cancer drug trials
• Cancer is life-threatening
• Not ethical to give no treatment (placebo)
• Many trials demonstrated increased survival with
  treatment
• New therapies must be compared with a current
  standard

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Procedures researchers have to follow

• Researchers must submit a trial protocol for
  independent scientific review
• The protocol is a carefully designed plan, that
  includes information on
• Aim of the research
• Treatment background
• How the study will be carried out
• How the results will be analysed

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Procedures researchers have to follow

• Slight variations exist from country to country.
  For example in the UK, the review is conducted by
  the Research Ethics Committee
• The panel consists of doctors, scientists, nurses
  and non-medical people
• The panel can ask for changes to the trial
  protocol
• Unexpected or serious events must be reported to
  the relevant body

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Informed consent

• Informed consent is a patients freely given
  agreement to participate in a given trial, based
  on a thorough understanding of what is to happen
• Consent is needed for every act of care performed
  by healthcare professionals

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The consent form

• The researcher will record that s/he has
  explained, and believes the patient understands,
  the study
• The patient is asked to sign and date the form to
  indicate his/her consent
• If a patient is incapable of giving
• informed consent, it must be
• obtained in writing from their legal
  representative

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Trial participants rights

• Trial participants are volunteers and have rights
  even after they have signed the consent form
• Patients have the right to say no to
  participating in the trial and do not have to
  give a reason
• Patients can withdraw from the trial at any time
  and do not have to give a reason
• The researcher will then discuss future treatment
  options

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Trial participants responsibilities

• Follow instructions and take study drugs as
  agreed
• Keep appointments or re-schedule them when needed
• Report any changes in health
• Report any lifestyle or practical issues that may
  inhibit participating in the study
• Ask questions if anything is unclear

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Questions patients should ask their doctor

• What is known about the new treatment?
• What are the possible side effects?
• Will the treatment benefit me?
• Will I have any extra investigations or tests?
• Who should I contact if something goes wrong?
• What happens to the information
• gathered in the trial?
• Will participating affect my health
• insurance?

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Benefits of participating in a trial

• The new treatment may work!

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Herceptin plus taxotere
Herceptin taxotere Taxotere alone/crossover
Taxotere alone
1.0 0.8 0.6 0.4 0.2 0
Probability Overall Survival
27.7
15.3
21.9
0 3 6 9 12 15
18 21 24 27 30
Months
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Benefits of participating in a trial

• May be only route to accessing new treatments
• Access to free medications / specialised testing
  that patients may not otherwise have access to
• Thorough documentation and supervision
• Treatment will be administered exactly according
  to the protocol, thus guaranteeing optimal
  benefit
• Control arm treatment (phase III) will be
  standard of care
• Chance to help others by furthering medical
  knowledge of breast cancer

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Benefits of participating in a trial

• There may be a survival benefit just by
• participating

100
90
80

Trial
70
No trial
60
50
10
0
2
4
6
8
Years
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Disadvantages of participating in a trial

• Study medication may not work or may be harmful
• Additional medical appointments may inconvenience
  participants schedule
• Some tests/ procedures are time-consuming and
  uncomfortable

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Disadvantages of participating in a trial

• Participants can only use treatments approved by
  the researchers while in the study
• Participants may not be able to continue
  receiving the study drug after the trial ends

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Patient confidentiality

• Trial participants are identified using patient
  identification numbers
• Research records are protected

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Clinical trials are a joint effort

• Doctors need patients to participate in trials
• Patients need trials to ensure better treatments
  available for the future

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Building Partnerships in Breast Cancer A Skills
Sharing Forum for Breast Cancer Patient Groups
www.breastcancer-forum.org