Current Topics in Clinical Research

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Current Topics in Clinical Research
prEN/ISO 14155 Parts 1-2Declaration of
HelsinkiHIPAA Privacy Rules

• Clinical Device Group Inc
• Evaluations for Medical Devices
• Biomedical Focus 01Minneapolis, MN

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prEN/ISO DIS 14155-Part 1

• Clinical Investigation of Medical Devices for
  Human Subjects
• General Requirements

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US Delegation

• Co-chairs
• Kimber Richter, FDA
• Nancy J Stark, CDG Inc

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Administrative

• Merged with ISO 14155
• Expanded for more depth and breadth
• Harmonized with ICH-GCPs
• Split into Part 1General Information and
• Part 2Investigational Plans
• Now ISO 14155 Parts 1 2

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Part 1 General Requirements

• Scope
• New definitions
• Adverse event
• Adverse device effect
• Serious adverse event
• Serious adverse device effect
• Justification for clinical study-literature
  review (Annex A)

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Part 1 General Requirements

• Current Declarations of Helsinki and Lisbon must
  be followed
• HelsinkiClinical Research
• LisbonPatient Rights
• Both published by World Medical Association
• Investigators must allow auditing

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Informed Consent

• Process
• comply with Helsinki
• avoid coercion or undue influence
• not waive subjects rights
• non-technical language
• ample time for consideration
• dated signature of subject or guardian
• provisions for emergency circumstances

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Informed Consent

• Content
• description/purpose of research
• forseeable risks
• potential benefits
• altenative therapies
• confidentiality
• compensation
• questions and/or termination
• new findings

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Informed Consent

• Informed consent statement
• participation is voluntary
• no penalty for refusal
• may discontinue at any time
• consequences of withdrawel
• acknowledgment of information provided
• May be separate document

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Documentation

• Investigators Brochure
• Clinical investigation plan (protocol)
• Curriculum vitaesigned
• EC opinion
• Correspondence
• Agreement
• Case report forms
• Adverse event reports
• Names/addresses of monitors
• Final report

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Responsibilities

• Sponsorunchanged
• Monitorunchanged
• Clinical Investigatorunchanged

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Annexes

• Literature review
• Information for ethics committees
• Final reports

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Literature Review

• Methodology
• establish a plan for identification, selection,
  collation and review of studies/data
• define objectives of the review
• establish selection criteria for articles
• assess articles per selection criteria

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Literature Review

• Evaluation of Literature
• justify exclusion of any documents
• review remaining documents
• identify any data gaps
• dated signature of authors

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Information for ECs

• Justification
• Health status of subjects
• Risks and mitigations
• Supervision
• Consent procedure and forms
• Confidentiality protections
• Consent process and documents
• Concurrent treatment of subjects
• Insurance
• Protocol
• Investigators Brochure
• Progress in final report
• All SAEs and adverse device effects

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Final Report

• Title page
• Summary
• Table of contents
• Introduction
• Materials methods
• Device description
• Protocol summary
• Results

• Discussion conclusions
• Abbreviations definitions
• Ethics statement
• Investigators administrative structure
• Signatures

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prEN/ISO DIS Part 2

• Clinical Investigation of Medical Devices for
  Human Subjects
• Clinical Investigation Plans

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Part 2-CIPs(Clinical Investigation Plans)

• New definitions
• Primary end point
• Secondary endpoint
• Follow-up period
• Point of enrollment
• Recruitment
• Clinical investigator
• Principal clinical investigator
• Coordinating clinical investigator
• Clinical investigation center

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Part 2-CIPs

• Monitoring arrangements
• Data and quality management
• Literature review
• Preclinical testing
• Objectives, design, statistics
• Early termination
• Publication policy
• Case report forms

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Annex

• Case report forms
• ID of study
• ID of subject
• Serial or lot number of device
• Subject selection/diagnosis
• Subject compliance
• Previous medication or treatment
• Baseline
• Concomitant illness, medication, treatment
• Procedures
• Findings
• Follow-up
• Adverse events and effects
• Signatures

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US Problems Issues

• No clear statement of purpose or underlying
  principlesjust a checklist
• Insufficient harmonization with ICH-GCPs
• Unclear definitions

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US Problems Issues

• Declaration of Helsinki
• FDA guidance Acceptance of Foreign Data March
  2001.
• Device studies must conform to Declaration of
  Helsinki of 1983
• Drug studies must conform to Declaration of
  Helsinki of 1989

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Voting Timeline

• Voting on ISO/DIS (initial draft) is in November
  2001
• FDAs vote will be no
• US vote will be yes with condition of immediate
  revision
• Voting of FDIS (final draft) in 2002

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Declaration of Helsinki
World Medical Association
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Revised October 2000

• Continuous review
• 1996 version not appropriate for developing
  countries
• Changing research environment genetics, data
  privacy.
• Harmonize with other CIOMS, ICH, other guidelines.

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Structure of 2000 Text

• 32 Articles
• 9 Introduction
• 18 Basic Principles for Medical Research
• 5 Additional Principles for Medical Research
  combined with Medical Care

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Article 1-Scope

• Medical research involving human subjects
  includes research on identifiable human material
  or identifiable data.

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Article 9-Legal Standing

• 1996 the standardsare only a guide physicians
  are not relieved from criminal, civil ethical
  responsibilities under the laws of their own
  countries.
• 2000 No national, ethical, legal or regulatory
  requirement should be allowed to reduce or
  eliminate any of the protections for human
  subjects set forth in this Declaration.

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Article 13-ECs

• Ethics committees
• Have right to monitor ongoing trials
• Must be given reports on SAEs.
• Must review information on funding, sponsors,
  institutional affiliations, other potential
  conflicts of interest and incentives for subjects.

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Article 16-Availability

• The design of all studies should be publicly
  available.

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Article 17-Cease Investigation

• Physicians should cease any investigationif
  there is conclusive proof of positive and
  beneficial results.

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Article 19-Benefit to Populations

• Medical research is only justified if there is a
  reasonable likelihood that the populations in
  which the research is carried out stand to
  benefit from the results of the research.

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Article 22-Information to Subject

• Each potential subject must beinformed of the
• sources of funding,
• conflicts of interest,
• institutional affiliations

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Article 24 25-Legally Incompetent

• Now includes
• Physically or mentally incapable
• Legally incompetent minor
• Should not be included unless research necessary
  to promote health of population, cannot be
  performed on others
• Subject to give assent if possible

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Article 26-Lack of Consent

• If no consent, proxy, or advanced consent
• Physical/mental condition must be necessary to
  research
• Protocol to explain reasons for inclusion
• Protocol to be approved by IEC
• Protocol to state consent to remain in study be
  obtained asap from subject or legal
  representative.

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Article 27-Publications

• Negative and positive results should be
  published.
• Sources of funding, institutional affiliations,
  conflicts of interest specified.
• Research not in accordance with Helsinki should
  not be accepted for publication.

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Article 29-Placebo

• new methodshould be tested againstbest proven
  prophylactic, diagnostic, and therapeutic
  methodsdoes not exclude use of placebo, or no
  treatment, in studies where no proven
  prophylactic, diagnostic or therapeutic method
  exists.

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Article 30-Ongoing Treatment

• At conclusion of the study, every patient entered
  into the study should be assured of access to the
  best proven prophylactic, diagnostic and
  therapeutic methods identified by the study.

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US Problems Issues

• Declaration of Helsinki
• FDA guidance Acceptance of Foreign Data March
  2001.
• Device studies must conform to Declaration of
  Helsinki of 1983
• Drug studies must conform to Declaration of
  Helsinki of 1989

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HIPAA Privacy Rules

• Health Information Portability and Accountability
  Act

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HIPAA

• 45 CFR Part 164Security Privacy
• Effective April 14, 2001
• Providers, insurers, information clearinghouses

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Enforcement

• Enforced by DHHS Office of Civil Rights
• Civil and criminal penalties
• Does not apply to sponsors

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Three Important Features

• Investigator access to medical records
• De-identified medical information
• Patient access to case report forms

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Access to Medical Records

• Protocol design process
• Estimates of enrollment capabilities
• Subject recruitment

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IRB Waiver

• Work is preparatory to research
• Medical records will not be removed from premises
• Access to medical records is necessary

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Requirements for Waiver

• Minimal risk to patients
• Privacy not adversely affected
• Research cannot be done without waiver
• Research cannot be done without access
• Privacy risks reasonable in relation to benefits
• Adequate plan to protect identifiers
• Adequate plan to destroy identifiers asap
• Written assurances that information will not be
  used or disclosed for other purposes

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Additions to Informed Consent

• Description of historical medical records needed
  for study
• Statement of when authorization expires
• Statement that treatment, payment, insurance,
  etc. not conditioned on signing
• Description of information that will not be
  disclosed.
• When/if crfs will be available to subject.

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Other Areas Affected

• Estimating subject availability
• Case report forms
• Leftover tissue samples
• Access to tissue banks
• Patient registries
• Consents
• Deceased persons

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De-identified Information

• Names
• Zip codes
• Months/days
• Phone fax s
• Email addresses
• SS numbers
• Medical record numbers

• Health plan numbers
• Account numbers
• Vehicle numbers
• Device serial numbers
• Web addresses
• Full face photos

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EU Data Privacy Directive

• EU Directive 95/46/EC
• Privacy rules make US compatible with EU

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Unchanged

• Adverse event reporting
• Device tracking
• Product recalls
• Repairs
• Replacements
• Post-marketing surveillance

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Uncertain Future

• Health-care industry opposed
• Implementation delayed once already
• Thompson says may need to review
• April 2001 Bush Whitehouse announces it will not
  ask for changes to regulations.

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Other US Happenings
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DHHS Offices

• proposed NOHRONational Office of Human Research
  Oversight
• OHRPOffice for Human Research Protections (Greg
  Koski)
• National Human Research Protection Advisory
  Committee
• Office of Research Integrity
• NBACNational Bioethics Advisory Commission
• OIGOffice of Inspector General

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NIH Offices

• OEROffice of Extramural Research

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New FDA Offices

• OHRTOffice for Human Research Trials (David
  LePay)
• Human Subject Protection and Good Clinical
  Practice steering committee (David LePay)

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Private/Other

• SUEESimplicity, Uniformity, Efficacy,
  Effectiveness
• proposed AHRPAssociation for Human Research
  Protection will act as a private accrediting
  group to accreditate clinical research systems at
  investigative sites

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The Human Research Pie
Pharma NIH Devices 75 16
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More Information

• www.clinicaldevice.com
• Or
• Njstark_at_clinicaldevice.com