GLUUD_and_ECRIN__DoH

ECRIN proposals for amendments to
the Declaration of Helsinki:
placebo, informed consent, transparency
Christian Gluud, Jacques Demotes-Mainard,
Vittorio Bertelé, Rita Banzi, Xavier Carné,
Silvio Garattini and ECRIN
Copenhagen Trial Unit, Denmark
European Clinical Research
Infrastructure (ECRIN)
ECRIN, an infrastructure supporting
international cooperation in clinical trials
• Connecting 23 national clinical reseach
infrastructures in Europe
• EU funded
• About 25 clinical trials
Declaration of Helsinki soon to –
and what 50 years!!!!
Proposals for amendments
to DoH
• Placebo
• Informed consent
• Transparency
• Thorough knowledge and clinical
relevance
• Risk of interventions
• Medical research limits the risks
• Independence and quality of research
ethics committees
Placebo (§32)
Problem: Clarification is needed to
prevent misuse of placebo
• Placebo, or no treatment, is acceptable
only in studies where no current
proven treatment exists
• The patients who receive placebo or no
treatment must not be subject to any
risk of harm (“serious or irreversible”
must be deleted!!)
Informed consent (§32)
Problem: Participants take risks without
expected benefits in non-inferiority and
equivalence trials
• The benefits, risks, burdens and
effectiveness of an intervention must
preferably be tested in a superiority
design rather than a non-inferiority or
equivalence design
• Patient information should explicitly and
unequivocally mention the use of a non-
inferiority or equivalence design, and its
absence of anticipated individual benefit
Transparency (§19) (§30)
Problem: Transparency is still lacking
• Clinical trial database must be compliant
with the World Health Organization
International Clinical Trial Register
Platform
• Registration must include the full protocol
and amendments
• Deposition of raw anonymised data for the
scientific community
Thorough knowledge and clinical
relevance (§12 and §31)
Problem: Most trial protocols lack
thorough knowledge and focus on
clinical relevance
• Thorough knowledge should be
obtained by systematic reviews when
relevant (§12)
• Clinical relevance should prevail over
methodological or statistical
considerations (§31)
Risk of interventions (§8)
Problem: No mention of the risks of
interventions in randomized clinical
trials and clinical practice
• The risks of interventions within and
outside randomized clinical trials do
not seem to differ
Medical research limits the risks
(§8)
Problem: No explicit mention in DoH of
the positive consequences of medical
research
• Medical research limits the risk of an
intervention to a relatively small
population for a relatively short time
• This is advantageous compared to the
introduction of an intervention into
clinical practice without sufficient
medical research backing the
intervention
Independence and quality of
research ethics committees (§15)
Problems: Many committees lack full
independence and sufficient training
• Research ethics committees must be
fully independent of the researcher, the
sponsor, their host institution, and any
other undue influence
• Its members must undergo appropriate
training
Thank you very much for your
attention and consideration!