s**********8
发帖数: 25265 | 1 Conflicts of Interest: Clinical Research
Policy
1. Investigator Conflicts of Interest
All Children’s Hospital investigators are required to disclose to Harvard
Medical School (HMS), on an annul basis, any potential conflicts of interest
. All investigators are required to adhere to HMS guidelines for managing
or eliminating specified categories of conflicts of interest.
In addition, to fulfill its obligations, the Committee on Clinical
Investigation (CCI) must address the impact of the investigator's financial
interests and other relationships on human subject protection. In many
cases, such interests and relationships will be barred or managed
independently of CCI review through institutional policies of Children's
Hospital or Harvard Medical School. However, in certain situations,
regulations or other standards that govern human subject protection may
treat a financial interest or relationship as potentially affecting human
subjects, even though Children’s Hospital and HMS institutional policies do
not prohibit it.
For example, compensation for serving as a company consultant to design a
protocol, particularly where company payments to the investigator will
depend on the outcome of the clinical research, raises special concerns for
the protection of human subjects. Those concerns require CCI attention even
though such consulting may be permitted under Harvard Medical School
conflict of interest guidelines.
Similarly, from time to time, the CCI reviews protocols in which an
investigator wishes to test, in children, a device the investigator has
invented. In some of these cases the device is not licensed to any company,
the investigator owns all or some of the patent rights, and the
investigator wishes to collect data that might ultimately support licensing
and development. This does not violate Harvard Medical School guidelines,
which are instead directed to regulating the financial and equity
relationships between the investigator and a company that is sponsoring
research or to which the device is licensed or "contractually committed."
Nonetheless, this is an issue for CCI review, since the design, conduct, and
results of the research protocol, and its effect on children, are
intertwined with the investigator's interest in developing and licensing the
invention, its regulatory approval, and (if the results of the trial are
favorable) the financial terms a company would offer the investigator to
license his or her patent rights.
Consistently, the Food and Drug Administration regulations list both types
of interest described above -- investigators’ intellectual property
interests, and payments dependent on research outcome -- as conflicts of
interest, and require that they be disclosed and managed. Recent draft
guidance by the federal Office of Human Research Protections also lists
these interests as among those that IRBs should understand, evaluate, and
manage in connection with review and approval of a protocol.
In the interests of protecting human subjects, the Committee on Clinical
Investigation requires that certain steps be taken to address such potential
conflicts of interest in clinical research.
As part of the current protocol application, an investigator must submit a
conflict of interest disclosure. As most recently revised, that form now
requires the investigator to disclose financial relationships or investment
interests in a research sponsor. It also requires disclosure of any
intellectual property interest in technology that is the subject of the
research (whether or not the technology is licensed), certain positions of
responsibility with the sponsor, and certain other interests that could
affect the research.
The CCI anticipates that an investigator's disclosures on the disclosure
form will generally be sufficient for the CCI to conduct its review without
further inquiries, and that investigator conflicts of interest may then be
addressed or managed concurrently with the CCI's review of the rest of the
protocol application.
When necessary, the Chair of the CCI or the Director of Clinical Research
Compliance (in consultation with CCI members and other clinicians, where
appropriate), will request the Vice President of Research Administration and
/or the Office of General Counsel to make further inquiries. Responsive
details will be provided to the Chair of the CCI and the Director of
Clinical Research Compliance for distillation or discussion with the CCI as
necessary. The sensitive nature of such information will be emphasized to
all those who review the material.
The Vice President of Research Administration will independently resolve any
issues raised by Harvard Medical School or other institutional conflict of
interest policies are not subject to CCI jurisdiction.
It is not the purview of the CCI to reinterpret or second-guess
institutional conflict of interest policies or their implementation. Rather
its function is to ensure that subjects and patients, the integrity of IRB
review, and the conduct of a trial are not jeopardized by an unidentified
and unmanaged conflict of interest. The CCI will therefore concentrate its
efforts on the elimination and management of those aspects of any conflict
of interest that may reasonably affect human subject protection.
As proposed in these guidelines, the sequence of steps to be taken by the
CCI to address a conflict of interest is as follows:
a. Where the investigator, as an interested party, is also the primary
source of information contained in the protocol (for example, concerning the
risks and benefits to subjects of a drug or device to be tested) and in
other circumstances as appropriate, the CCI may require that independent
scientific review verify the investigator's representations of risks and
benefits, assess the impact of the research design on subject burdens and
benefits, and identify any critical points in the protocol in which the
conflict of interest, if acted upon, could have a material adverse impact on
the clinical care of the subject. The precise form of scientific review
may vary. The independent review may occur as part of the departmental
review, if the reviewers are appropriately aware of the nature of the
conflict, or it may occur in other ways, including referral to the clinical
research support office.
b. Where the investigator, as an interested party, also has significant
clinical involvement in the care of subjects under the protocol, the CCI may
require that an independent data safety monitoring process be established
for reviewing adverse events, validating the application of inclusion and
exclusion criteria, performing interim analyses of the integrity of the data
, and assessing any potential effects on the clinical care of subjects. In
this context, or for purposes of later reporting on continuing review, the
CCI may consider requiring the collection of additional data that would
document whether a conflict of interest has had any effect on subjects or
the research.
c. Where applicable, the informed consent must disclose that the
investigator is the inventor of or has an interest in a related patent, that
the investigator and /or Children's Hospital, as applicable, may receive
financial benefits from development of the invented technology, and that the
financial benefit may depend on the outcome of the trial.
The following language is recommended for cases in which an investigator has
an intellectual property interest:
As [an inventor of the technology], Dr. Z has a financial interest in _____
______ technology that is used in this research study. In the future it is
possible that this technology will be sold commercially, and that the
results of this trial will be important in securing government approval or
contracting with a business to manufacture or develop the technology. If
this were to occur, Children's Hospital and/or the investigator might
receive financial benefits in the form of royalties or other compensation.
As in all research studies, the Hospital has taken steps designed to ensure
that this potential for financial gain does not endanger research subjects,
or undercut the validity and integrity of the information learned by this
research.
In other cases, the CCI may require the informed consent to state the
general nature of the interest.
d. The CCI may require that someone other than an investigator who has a
financial relationship, intellectual property interest, or investment
interest, serve as the principal investigator (PI), perform certain of the
functions otherwise designated for the investigator (such as enrollment), or
engage in supplementary oversight roles, particularly where subject safety
would otherwise depend solely on clinical judgments made by an investigator
with a conflict of interest.
e. In treatment protocols where the risks are significant and medical
circumstances warrant, the CCI may request that the investigator, the
sponsor, or the department provide a mechanism for the ongoing monitoring of
the clinical care of the subjects against the effects of any potential
conflict of interest, through peer reviewed or other concurrent clinical
processes not triggered simply by reported adverse events, and may condition
approval on implementation of such a process as approved by the pertinent
Chief. This may take the form of an enhanced data safety monitoring plan,
which includes broader review of clinical data pertinent to risks; or, where
the conflict may raise or appear to raise significant questions about
whether clinical care of subjects may be subordinated to research objectives
to the detriment of patients, the CCI may condition its approval on
periodic reporting of the results, or sufficiently concurrent departmental
or other clinical review.
f. As part of the CCI deliberations, the committee will consider the
particular protocol, associated risks, and the potential for risks and
benefits, and determine whether any or all of the above mentioned safeguards
, or any others appropriate under the particular circumstances, should be
required as part of the approval process. The CCI may, for example,
consider any other remedies it would ordinarily have available, such as
conditioning approval on a process to manage or eliminate other effects of a
conflict, requiring consent monitoring, or requesting information about how
sponsors or their agents will mitigate or monitor for risks presented.
This protocol has been (1) approved for submission to the Committee on
Clinical Investigation, and (2) the PI has completed and submitted a
Research Disclosure Form to me that I have reviewed and determined that no
actual or potential conflict of interest exists.
_________________________________________ _____________
Signature of department Chairperson/Division Chief Date
Definitions
2. Definitions of Terms used in Financial Disclosure Forms
Protocol is defined as the protocol submitted with the disclosure form and
includes the study to be conducted under the protocol.
You is defined to include the investigator and members of his or her
immediate family (i.e., spouse, children, persons with whom he or she
maintains living arrangements that approximate a family relationship).
Person affiliated with is defined to include all personnel who will work on
research under the protocol and members of their immediate families.
Proprietary interest is defined to include inventions, discoveries, patents,
copyrights, and licenses. Investigators are asked to include these
interests even if they are assigned to someone else (e.g., an academic
employer; subject to a royalty-sharing policy). Such interests should also
be included whether they are licensed or unlicensed, and whether their
ownership is direct or indirect (e.g., through a development partnership or
small corporation).
The form asks about investments, financial relationships, advisory roles,
and appointments. While these are not defined, they should be understood
broadly, and in a "common sense" way.
For example, questions that ask about investments are seeking information
about stocks, options, and any kind of security in which the investigator
has a direct or indirect interest. Investigators can exclude only publicly
traded mutual funds. Similarly, questions about financial relationships are
directed towards any arrangement under which the investigator receives any
form of compensation.
3. Procedures when the Hospital owns Equity
Children's Hospital will not generally participate in clinical trials of a
test article sponsored by a licensee in which the Hospital holds license-
related equity except in extraordinary situations, as demonstrated by the
presence of all of the following circumstances: (1) there is no other venue
that is appropriate for the study, or there are other compelling reasons
why Children’s Hospital must be a possible venue, such as ensuring access
for vulnerable or affected populations; (2) the test article, whether a drug
or device, is of significant potential benefit for the public or Hospital
patients; (3) there is independent verification and monitoring of all
significant aspects of the study relevant to human subject protection and
scientific integrity, including protocol design, description of risks and
benefits, implementation of exclusion and inclusion criteria, securing
informed consent, criteria and procedures for subject withdrawal, reporting
and addressing adverse events, maintaining research subjects’ awareness of
their rights, and reporting of data; and (4) the Hospital Institutional
Review Board, in its sole discretion, has approved the study, and whatever
additional conditions the Hospital Institutional Review Board has imposed
are satisfied.
In deciding whether to participate in a clinical trial sponsored by a
company in which Children's Hospital owns such licensee equity, the
Committee on Clinical Investigation will independently evaluate whether the
criteria above have been met; the requirements and standards of regulatory
and accrediting bodies, and its own policies; the adequacy of the Hospital’
s and the clinical department’s steps to ensure that impacts of a potential
conflict have been and will be effectively mitigated; the conflict’s
impact on the validity and integrity of the data generated from the clinical
trial, to the extent such data contributes to the potential benefit of the
study; how to implement full disclosure of the Hospital’s equity interest
to subject patients and others; and how to ensure that there is no
inappropriate preferential access to patient populations for companies in
which the Hospital owns equity.
Under no circumstances may any clinical trial be overseen solely by an
inventor of a test article that is the subject of the trial. Except in
extraordinary circumstances in which the inventor’s involvement is
necessary to assure the safety of subjects because of the inventor’s unique
knowledge of a device or other test article, an inventor should not be the
principal investigator in the clinical trial concerning that test article,
nor should the principal investigator be directly or indirectly supervised
by an inventor.
It is expected that confirmatory clinical trials (typically Phase II and
Phase III studies) will be conducted as multi-center studies and directed by
principal investigators who have no affiliation with the hospital.
Informed Consent Statement if Children's Hospital Owns Equity:
Children’s Hospital licenses certain of its research discoveries to
companies for research and/or commercial development. From time to time,
Children’s Hospital receives equity, either as capital stock or as options
to buy capital stock, as partial consideration for a license. In keeping
with Children’s Hospital policy, you are advised that Children’ s Hospital
has equity in the company that is sponsoring this research and may gain
financial (monetary) benefits if the drug/device/technology being studied in
this trial proves to be of benefit. As in all research studies, the
Hospital confirms that it has taken, and will continue to take, all
necessary steps to ensure research subject safety, and the validity and
integrity of the information obtained by this research.
4. IRB Member Conflicts of Interest
As part of new member orientation, all new members are informed about the
policy on conflicts of interest. The members are informed that any IRB
member, voting or nonvoting, with a conflict of interest in a study, must
leave the room during the final discussion and vote on the protocol, unless
that conflict has been discussed with and cleared by the Chair of the IRB.
A member with a conflict may be asked questions about the content of the
protocol, and issues concerning the study, but must not be present beyond
the questions and answers, and, other than to provide information, must not
seek, inside or outside the meeting, to influence or affect the voting of
nonconflicted members. Any individual member with a conflict of interest
must leave the room for the final discussion and vote. The minutes must
document the fact that the member left the meeting room during the final
discussion and vote because of a conflict of interest.
A conflict of interest for an IRB member is defined to include the member
and his or her immediate family (i.e., spouse, children, persons with whom
he or she maintains living arrangements that approximate a family
relationship).Conflicts include service as an investigator, coinvestigator,
or consultant to the study before the IRB; financial relationships or
investment interests in the study’s commercial sponsor that would trigger a
disclosure under Harvard Medical School guidelines (generally $20,000 in
income, any unregistered equity, or registered equity greater than $20,000
in value); any pending or anticipated negotiation or agreement with the same
commercial sponsor for clinical research, consulting services, speeches, or
any other matter; and current receipt of a substantial portion of their own
research monies (greater than 20%) from the same commercial sponsor.
Document Attributes
Title Conflict of Interest: Clinical Research
Author Susan Kornetsky Dates Reviewed/
Revised 04/01/05
Reviewed/
Revised by Susan Kornetsky
Copyright ©Children's Hospital Boston, 2011
Last Modified 06/20/05
Approved
Susan Kornetsky
Director of Clinical Research Compliance
Carleen Brunelli, MBA, PhD
Vice President for Research Administration
http://www.childrenshospital.org/cfapps/research/data_admin/Sit | s**********8
发帖数: 25265 | 2 a lot of good stuff in this doc
interest
financial
【在 s**********8 的大作中提到】
: Conflicts of Interest: Clinical Research
: Policy
: 1. Investigator Conflicts of Interest
: All Children’s Hospital investigators are required to disclose to Harvard
: Medical School (HMS), on an annul basis, any potential conflicts of interest
: . All investigators are required to adhere to HMS guidelines for managing
: or eliminating specified categories of conflicts of interest.
: In addition, to fulfill its obligations, the Committee on Clinical
: Investigation (CCI) must address the impact of the investigator's financial
: interests and other relationships on human subject protection. In many
| k****i
发帖数: 1126 | 3 A lot of good stuff on this board, which will take me time to digest all of
them.
Thanks!
【在 s**********8 的大作中提到】
: a lot of good stuff in this doc
:
: interest
: financial
|
|
