Attack of the Data Suckers
A Deeper Look at the ICMJE’s Proposal
The International Committee of Medical Journal Editors (ICMJE) recommended
several measures to ensure that clinical
trials data is shared responsibly – and the
rights of both clinical trial participants and
conductors are protected.1
“The ICMJE believes that there is an
ethical obligation to responsibly share
data generated by interventional clinical trials because participants have put
themselves at risk,” the members wrote
in The New England Journal of Medicine.
According to the proposal, a clinical trial
report should meet the following conditions in order to be considered for publication in one of its member journals:
• Authors must share with others the
de-identified individual-patient data
underlying the results presented in
the article (including tables, figures,
and appendices or supplementary
material) no later than 6 months
after publication.
• Authors must include a plan for data
sharing as a component of clinical
Lyophilized Powder for Solution for Intravenous Injection
ADVERSE REACTIONS
Brief Summary of Prescribing Information: Please see
package insert for full Prescribing Information.
Common adverse reactions observed in greater than 5% of
subjects in the clinical trial were development of inhibitors to
porcine factor VIII.
INDICATIONS AND USAGE
OBIZUR, Antihemophilic Factor (Recombinant), Porcine
Sequence, is a recombinant DNA derived, antihemophilic
factor indicated for the treatment of bleeding episodes in
adults with acquired hemophilia A.
Limitations of Use:
Clinical Trials Experience
Because clinical trials are conducted under widely varying
conditions, adverse reaction (AR) rates observed in the clinical
trials of a drug cannot be directly compared to rates in the
clinical trials of another drug and may not reflect the rates
observed in clinical practice.
CONTRAINDICATIONS
The safety and efficacy of OBIZUR was evaluated in a multicenter, prospective, open-label, clinical trial that investigated
adult patients with acquired hemophilia A. Twenty-nine adult
subjects were enrolled in the study, received at least one dose
of OBIZUR and were evaluable for safety. Of the 29 adult
subjects, 10 were between the ages of 40 and 65, and 19 were
65 years of age or older (18 Caucasian, 6 African-American,
and 5 Asian). Ten (34%) subjects were female.
OBIZUR is contraindicated in patients who have had lifethreatening hypersensitivity reactions to OBIZUR or its
components (including traces of hamster proteins).
The most frequently reported adverse reaction in patients
with acquired hemophilia A was the development of inhibitors
to porcine factor VIII.
WARNINGS AND PRECAUTIONS
Immunogenicity
• Safety and efficacy of OBIZUR has not been established in
patients with baseline anti-porcine factor VIII inhibitor titer
greater than 20 BU.
• OBIZUR is not indicated for the treatment of congenital
hemophilia A or von Willebrand disease.
Hypersensitivity Reactions
Hypersensitivity reactions can occur with OBIZUR. OBIZUR
contains trace amounts of hamster proteins. Early signs of
allergic reactions, which can progress to anaphylaxis, include
angioedema, chest-tightness, dyspnea, hypotension,
wheezing, urticaria, and pruritus. Immediately discontinue
administration and initiate appropriate treatment if allergic
or anaphylactic-type reactions occur.
Inhibitory Antibodies
Inhibitory antibodies to OBIZUR have occurred. Monitor
patients for the development of antibodies to OBIZUR by
appropriate assays. If the plasma factor VIII level fails to
increase as expected, or if bleeding is not controlled after
OBIZUR administration, suspect the presence of an antiporcine factor VIII antibody. If such inhibitory antibodies
to anti-porcine factor VIII are suspected and there is a
lack of clinical response, consider other therapeutic options.
Monitoring Laboratory Tests
• Perform one-stage clotting assay to confirm that adequate
factor VIII levels have been achieved and maintained.
– Monitor factor VIII activity 30 minutes and 3 hours after
initial dose.
– Monitor factor VIII activity 30 minutes after
subsequent doses.
• Monitor the development of inhibitory antibodies to
OBIZUR. Perform a Nijmegen Bethesda inhibitor assay if
expected plasma factor VIII activity levels are not attained
or if bleeding is not controlled with the expected dose of
OBIZUR. Use Bethesda Units (BU) to report inhibitor levels.
All subjects were monitored for development of inhibitory
antibodies to OBIZUR using the Nijmegen modification of the
Bethesda inhibitor assay. A subject was considered to have
developed an OBIZUR inhibitor if the titer was ≥0.6 Bethesda
Units (BU)/mL.
Of the 29 subje cts treated with OBIZUR, 19 subjects were
negative for anti-porcine factor VIII antibodies at baseline.
Five of the 19 (26%) developed anti-porcine factor VIII
antibodies following exposure to OBIZUR. Of the 10 subjects
with detectable anti-porcine factor VIII antibodies at baseline,
2 (20%) experienced an increase in titer and eight (80%)
experienced a decreasing to a non-detectable titer.
All subjects were also monitored for development of binding
antibodies to baby hamster kidney (BHK) protein by a
validated sequential ELISA (enzyme-linked immunosorbent
assay). No patients developed de novo anti-BHK antibodies.
The detection of antibody formation is highly dependent on
the sensitivity and specificity of the assay. Additionally, the
observed incidence of antibody (including neutralizing
antibody) positivity in an assay may be influenced by several
factors, including assay methodology, sample handling,
timing of sample collection, concomitant medications, and
underlying disease. For these reasons, comparison of the
incidence of antibodies to OBIZUR with the incidence of
antibodies to other products may be misleading.
Baxalta and Obizur are trademarks of Baxalta Incorporated.
Manufactured by:
trial registration, including noting
where the researchers will house the
data and, if not in a public repository,
the mechanism by which they will
provide others access to the data
• Authors must include a description
of the data-sharing plan in the
submitted manuscript. Authors may
choose to share the de-identified
IPD underlying the results presented
in the article under less restrictive,
but not more restrictive, conditions
than were indicated in the registered
data-sharing plan.
De-identifying patient data protects
the confidentiality of trial participants,
and the ICMJE also seeks to protect
the rights of investigators and trial
sponsors, with the following actions:
• ICMJE editors will not consider the
deposition of data in a registry to
constitute prior publication
• Authors of secondary analyses
using these shared data must
attest that their use was in
accordance with the terms (if any)
agreed to upon their receipt
• Authors must reference the
source of the data using a unique
identifier of a clinical trial’s dataset
to provide appropriate credit to
those who generated it and allow
searching for the studies it has
supported.
• Authors of secondary analyses
must explain completely how theirs
differ from previous analyses.
And, in a case where these criteria are
not being met, the ICMJE proposes
that journal editors request additional
information; publish an expression
of concern; notify the trial sponsors,
funders, or institutions; or, in certain
cases, retract the publication.
“Data sharing is a shared responsibility,” the members concluded. “Done
well, sharing clinical trial data should
also make progress more efficient
by making the most of what may be
learned from each trial and by avoiding unwarranted repetition. It will help
to fulfill our moral obligation to study
participants, and we believe it will
benefit patients, investigators, sponsors, and society.”
REFERENCE
1. Taichman DB, Backus J, Baethge C, et al. Sharing clinical trial
data: a proposal from the International Committee of Medical
Journal Editors. N Engl J Med. 2016;374:384-6
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