Learning Center
Plans & pricing Sign in
Sign Out



       for Clinical Trials CHIP Trial 10th December 2007
Legal Issues
 Consent and Clinical Trials
Medicines for Human Use (Clinical Trials) Regulations 2004 Schedule 1
  part 1 paracraph (3) 1
   A person gives informed consent to take part in a clinical trial only if
   his decision is given freely after that person is informed of the
   nature, significance, implications and risks of the trial;

European Union Clinical Trials Directive 2001/20/EC
    Written consent must be given by parents or those with legal
   responsibility for the child, but children should also give their assent
   (the voluntary permission given by one who is old enough to
   understand and know if they want to take part or not)

DOH Seeking Consent working with children 2001 consent to be valid:
     Capacity - Capable of taking that particular decision (competent)
     Voluntary - not under pressure duress of anyone
     Informed - enough information to make the decision
Medicines for Human Use (Clinical Trials Regulations) 2004
Informed consent in clinical trials
S.I.2004:1031 as amended by S.I.2006:1928 and S.I.2006:2984.

 Good Clinical Practice legal requirement part 4 eg 20 elements

Minors Clinical Trials – Minor person under age 16 years
‘special protection’

 Not included if the same results can be obtained using persons capable of
  giving consent.
 Normally included only when IMP direct benefit to the patient, outweighing
  the risks.

 Need for clinical trials involving children to improve the treatment available
  to them.
 Medicinal products which are likely to be of significant value for children are
  fully studied.
 Carried out under conditions affording the best possible protection for the

Conditions and Principles -
 ‘6’ information according to capacity to understand from
  staff with experience with minors
 ‘8’ No incentives of financial inducements.
 ’13’. Informed consent by parent/ legal representative
  shall represent the minor’s presumed will.
 ’16’ The interests of the patient always prevail over those
  of science and society.
Parental Responsibility
Children‟s Act 1989 - Part 1 Responsibilities for Children
 Married Parents
 Unmarried mother
 Unmarried father if acquired by agreement order in accordance with
  the provisions of this Act.
 Residence order (part 1 8,& 12 the father or another person)
 Local Authority if the child is in care ( Part 1 section 31 & 33)

Adoption and Children Act 2002
 Unmarried father if registered on birth certificate (effective from Dec
  2003 – but not if born before 2003)

N.B new born may not yet have a birth certificate
Hierarchy of informed consent for a minor
Medicines for Human Use Clinical Trial Regulation (2004)

 Parent or person with parental responsibility - should always be
  approached if available.

 Personal legal representative – emergency situations only person not
  connected with the conduct of the trial who is:
 (a) suitable to act as the legal representative by virtue of their relationship
  with the minor, and
 (b) available and willing to do so.
 May be approached if no person with parental responsibility can be
  contacted prior to the proposed inclusion of the minor, by reason of the
  emergency nature of the treatment provided as part of the trial.

 Professional legal representative
 A person not connected with the conduct of the trial who is:
 (a) the doctor primarily responsible for the medical treatment of the minor,
  or may be approached if no person suitable to act as a personal legal
  representative is available.

 (b) a person nominated by the relevant health care provider (e.g. an acute
  NHS Trust or Health Board).
Capacity and Children
 Assessing Capacity -     Mental Capacity Act 2005 (2006) 4 aspects:
    Understand the information relevant to a decision
    Retain that information
    Use or weigh the information as part of the process of making a
     decision „typically interpreted as “orientated in reality”.
    Be able to communicate the decision

 Good practice to involve their families in decision making.

 A person with parental responsibility can take that decision for them until
  aged 18 yrs

 Best Interest - Clinician can provide treatment and care
 Age under 16years are not presumed to be legally competent unless they
  have sufficient understanding and intelligence to enable him or her to
  understand fully
 No specific lower age it depends on the seriousness and complexity of the
  treatment being proposed.

 Consented for a trial then must be reconsented at 18years
Child’s Capacity ‘competence’
‘a minor can provide valid consent provided they are competent ie of
sufficient intelligence and understanding to understand what is
proposed (House of Lords)

Consent to Treatment Gillick v west Norfolk and Wisbech AHA 1985
Refusal of Treatment if Gillick Competent
• Refused treatment for anorexia
 Lord Donaldson drew an analogy between consent and a flak jacket to
  protect medics from civil or criminal action.. ‘a competent minor can
  provide this protection but so too can the patients parents or the courts’
  and treatment was authorised in best interests.
 The result of this case means that a competent minor cannot always
  refuse treatment where consent has been provided from an alternative
  legally valid source.
 BUT No test case for clinical trials
 Clinical Trials Consent if the child refuses is difficult to argue ‘best
ICH GCP (4.8.5)

‘The Investigator or a person designated by
  the investigator should fully inform the
  subject and the written informed consent
  form should be signed and dated by the
  person who conducted the informed
  consent discussion’
20 Elements of informed consent ICH 4.8.10
 Involves research
 Purpose of the trial
 Treatment and the probability of random assignment
 Trial procedures
 Subjects responsibility
 Experimental aspects of the trial
 Risks or Inconveniences – including the nursing infant
 Expected benefits – especially when no intended clinical
  benefit to the subject
 Alternative treatments available
 Compensations available for trial related activity
   Prorated payment (just adults)
   Expenses
   Voluntary participation in the trial may withdraw at any time
   Must agree to direct access to medical records
   Trial records will be kept confidential
   Will be informed of any new information in a timely manner
   Contact person
   Reasons for termination of participation
   Expected duration of participation
   Approximate number of subjects involved in the trial

 Information - oral and written
                  Information Sheet parent + age <5 / 6-12/ 13- 15 years
                  use information sheet to guide your ‘informed consent’
 Ample time – deemed to be 24 hours but
                - situation dependent (emergency)
 No –coercion also not obliged
 Check their understanding
 Signed and dated by subject (or witnessed)
 Consent form filed:
                 study site file
                 patient copy
                 medical records
       Plus trial co-ordinating centre if requested (recently agreed)
 Continuous Process – during intervention and follow up
                           - pre admission and post admission
‘Researchers …should see the giving of
 informed consent as a process, not as an
 event; regular updates and reinforcement
 increase parental understanding and
 facilitate continuous participation.. The
 informed consent process is not merely
 reading and signing a form, but it a
 continuous dialogue which takes place
 over time'. Yeung 2007
Improving the Quality of consent to RCT by using
Continuous Consent
Allmark and Mason 2006
   Toby Trial – neonatal asphyxia treated with full body cooling 34oC
   Continuous consent – information given at 3 different stages
   Consented within 6 hours of birth
   Mothers ‘validity’ affected by opoids /traumatic birth /very sick infant
   Findings:
   48% no knowledge of side effects before signing
   13% did not recall receiving an information sheet before signing
   Validity 73% mothers 8% fathers problems at signing
   Reduced to 24% mothers and 15% fathers at later stage
   Recommends informed consent as a process
Nurses Consenting
‘Confident Competent and Delegated’
             and ‘willing’
  Confident & Competent
       Audit trail for training in consent, GCP and protocol >
       UKCRN course on 16th January 2007 or on line
       Specified qualifications in protocol +/- i.e. ENB 415
       Assessed by Principal Investigator
       Aware of the risks and responsibilities

     Delegation Log or specific Trust Documentation >
     Ethics Form SSA states persons consenting
     CV on Site Master File

    ‘The medical care given to and medical decisions made of behalf of
       subjects shall always be the responsibility of an appropriately qualified
       doctor‘ MHU(CT)Regulatio 2004
    MHRA expect a medic to make the eligibility decision and to record it!!
Nurses Consenting
 Royal College of Nursing
        Indemnify Nurses for clinical trials but not the trial
        not phase 1 First into man studies - ? unlicensed or off label
   see Informed Consent in Health and Social Care Research 2006
 NMC legal advisors –
        Professional Code of Conduct - accountability
        „ delegated to suitably qualified person‟ (Declaration of Helsinki)
 Medicines for Human Use Regulatory Agency Regulation (2004:1031)
         adequate training re protocol and GCP
         delegated formally by investigator
         *physician answers medical questions the nurse cannot answer
         procedure approved by ethics
         *subjects capacity – if in doubt then a physician must consent
 Training- in the protocol and consent with Audit Trail
       GCP/Consent law & process / clinical skills
       Investigational Medicinal Product
       Nature, significance implications risks & benefits
       Treatment choices
       Serious adverse events
       Process of taking informed consent (focus on legislation
                        pertinent to vulnerable ‘paediatric populations’
       Knowledge and experience to allow the participant to make a
             fully informed choice about participating in the trial
       Documented training in relevant laws Regulations and GCP
                             (data protection and confidentiality)
Consenting for IMP‟s
12 Key Points on Consent the law in England DOH

‘you may seek consent on behalf of a colleague if
  you are capable of performing the procedure in
  question or if you have been specifically
  trained to seek consent for that procedure’.

  This resolves the concern that a nurse may not
  take consent in relation to a clinical trial for a
  drug that she may not prescribe.
 Trial protocol & SOP – adhere to what they say

 Trust Consent Policy – preferably state ‘Clinical Trials IMP’s’
                       - specific delegation form
 Trust R & D Governance Approval (protocol)
 Research Ethics Committee Approval (consenters listed on SSA)

 Delegation log PI ensure written evidence of education and
  training (CV’s +)

 Person taking consent must sign the consent form (RCN)
Document the process……………….
Continuous Negative Extra-thoracic Pressure Professor Southall

   Baby breathing aid study cleared -
   BBC News
         Carl and Debbie Henshall, of Clayton
         in Staffordshire, recently won an
         Appeal Court hearing which said the
         GMC should review its decision to
         reject their complaints that doctors
         did not give properly informed
         consent to medics for their girls to
         take part.

         ‘None of the investigations has
         supported parents' claims they were
         misled and consent forms forged’
CHIP – effective consent
Capacity -    Post admission parents distressed /traumatised
              Ample time - pre admission clinics
              Parental Responsibility to consent & Child‟s competence to assent

Informed –    Risks balanced against benefits > parents
              Adult study Van den Berghe Trial 2001
              Benefits of patients in studies + additional monitoring
              MCRN – Paediatric Regulations EU need for studies
                      - Adoption process
              Unlicensed and off label
              Use information sheet as a guide (consider parents initialling)
              Make a checklist for each patient and sign yourself
              Translators or Interpreters

Voluntary –   empowers parents to have control to withdraw at anytime / choice

Data Protection – if not a member of the clinical team consider Caldicott
                        - patient information from Consultant
Allmark & Mason 2007

 ‘Our main concern was whether it would have side effects,
 that was our main concern; any side effects and we
 wouldn’t have given our consent.’ (Father: 11)

 For other parents, the situation may have seemed so severe
 that side effects were of little importance to them:

 ‘We fully understood what he wanted to do in terms of
 treatment … we fully understood the side effects if there
 was going to be any, or the risks involved, but obviously
 whatever anyone tells you all you listen to is that your child
 is damaged’ (Mother: 2)
Promote the Trial within the team
   Research Team and Clinical Team
       recruit up to day 5 -eligibility
                 V–      Ventilated
                 I-      Inotropes
                 T–      Twelve hours minimum on PICU
                 A-      Arterial Line
                 L5      Less than 5 days since admission
 Retrieval Team /Transport
 Document clearly what you /they have said (follow info sheet)
 If legal action a nurse will be scrutinised more than a Principal
 Document the person has refused to avoid ‘over asking’
 A patient refusing to give their consent to a trial is not
  a sign that you have failed but it may indicate that you
  were conscientious enough to ensure that they are
  properly informed to make a free decision.

 Large numbers of patients refusing may indicate a
  problem with the study.

(BMJ 1995;311:734-737 16 September)

    Seeking consent working with children 2001
    Good Practice in consent implementation guide consent to examination
     or treatment 2001

   RCN Informed Consent in health and social care research
   Yeung V Paediatric Drug Handling (2007) Pharmaceutical
     Press 1st edition p 86-119
   P Allmark and S Mason Improving the quality of consent to
     RCT by using continuos consent and clinical training in the
     consent process J Med Ethics 2006 32: 439 -443

To top