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Patient Rights and Access to Investigational Drugs and Medical Devices: Is There a Problem With the Current System?


Patient Rights and Access to Investigational Drugs and Medical Devices: Is There a Problem With the Current System? Bruce Patsner, M.D., J.D. Research Professor – PowerPoint PPT presentation

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Title: Patient Rights and Access to Investigational Drugs and Medical Devices: Is There a Problem With the Current System?

Patient Rights and Access to Investigational
Drugs and Medical Devices Is There a Problem
With the Current System?
  • Bruce Patsner, M.D., J.D.
  • Research Professor
  • University of Houston Law Center
  • September 24, 2008

  • The medical and legal opinions in this talk are
    those of the author alone, and do not represent
    the views of the University of Houston Law
    Center, the United States Food and Drug
    Administration, or any other physician, attorney,
    academic, or government official

Question Is there a problem that needs a
  • Is there any hard evidence that the current
    system does not work for
  • Unapproved experimental medical devices?
  • Unapproved investigational drugs?
  • What are current options, and what are the

The Abigail Alliance Litigation
  • Legal issue do terminally ill patients have a
    constitutional right to unapproved
    investigational drugs?
  • A patient interest group sued FDA in federal
  • A 22 year old girl with a progressive head and
    neck cancer wanted access to Iressa and to
    Erbitux, drugs not approved at the time
  • Father brought suit, later joined by experienced
    anti-regulatory group Washington Legal Foundation
  • Wanted access to drugs after Phase I testing WLF
    acknowledged that in rare cases patients might
    want access to drugs in Phase I testing as well

What was being proposed in Abigail Alliance as a
  • Would have enjoined (prevented) FDA from barring
    sale of investigational drugs to terminally ill
    cancer patients after only Phase I testing
  • No change in informed consent requirements even
    though no real safety or efficacy data known
  • ?waiver of liability for physicians to be worked
    out later

Abigail Alliance for Better Access to
Developmental Drugs v. von Eschenbach 445 F.3d
470 (2006)
  • Brought in federal district court in District of
    Columbia in 2003 after FDA failed to respond to
    Citizens Petition
  • Case dismissed by federal district because no
    constitutional right existed so there was
    failure to state a valid claim
  • On appeal to D.C. Circuit Court of Appeals 2-1
    decision IN FAVOR OF plaintiffs rocks the medical
    community. LOTS of writing on this in the
    throw-away journals.
  • Arguments raised by FDA against, and consumer
    groups for, were both legal, medical, and

Arguments advanced by plaintiffs Legal
  • ?Denying access to drugs deprived patients of
    right of self-defense or self-preservation
  • ?Due process clause protects the right of such
    patients in late stages of disease to decide for
    themselves whether to assume the risks of
    unapproved drugs. Denial denied patients 5th
    Amendment due process right to life, liberty,
  • ?Dying cancer patients had unique riskbenefit
    calculus, and Supreme Court has already ruled
    that patients have a right to die by refusing
    medical treatments (Cruzan case). These patients
    have special latitude
  • ?NO privacy rights/ bodily integrity arguments
    raised, interestingly enough

Arguments advanced by Plaintiffs Practical
  • Terminal cancer patients should have ability to
    opt for new treatment that meets a lower
    evidentiary hurdle than that required for new
    drug marketing
  • Current regulatory system does not provide
    special provisions based on risk of injury or
    death from disease
  • Current system doesnt work because patients
    cannot find appropriate clinical trials, live too
    far from research centers, or do not meet
    eligibility criteria. Also, sometimes their
    physicians refuse to patients request
    compassionate use

Arguments Raised by FDA and Others in Defense
  • Constitutional right to unapproved drugs was
    rejected firmly by Supreme Court in Rutherford v
    U.S. 1980 (laetrile case)
  • No Constitutional right to drugs even if
    physicians want patients to get it too and even
    if state laws approve (Gonzales v. Raich 2005
    medical marijuana case)
  • Prescription drugs generally cannot be sold
    (marketed) until they are approved, according to
    amended 1938 Federal FDCA
  • Informed consent and tort liability issues

Arguments Raised by FDA and Others in Defense
  • Right claimed by Abigail Alliance underestimates
    toxicities/risks, and overestimates success rate,
    of these drugs. There is no more unique risk
    benefit ratio for terminally ill cancer patients
    than other desperately ill patients whove
    exhausted options
  • Would undermine entire drug approval process no
    incentive to participate in Phase II and III
    trials, even if not placebo-controlled
  • Would create black market, and subject ill
    vulnerable patients to fraudulent claims
  • Will never get accurate safety and efficacy data
    for the drugs
  • Patients will doctor shop in order to make an
    end run around physicians who legitimately
    believe the drug is either too dangerous, has no
    chance of working, or both
  • There ALREADY ARE multiple programs in place that
    work and are readily accessible. Lots of options
    for docs/patients

The 2-1 D.C. Circuit Court of Appeals Decision
  • Terminally ill patients do have a right to
    potentially life-saving experimental drugs even
    when very risky
  • Throughout most of U.S. history government has
    not blocked access to these drugs
  • Patients have a right to make life-or-death
    decisions free from government interference
  • There is a due process right which can be
    inferred from the Cruzan decision and a patients
    right to REFUSE medical treatment
  • Dissent no history of a right to experimental
    drugs. FDA has a rational basis for ensuring
    there is acceptable evidence about risks and
    benefits of drugs
  • For a while, this decision WAS the law in the U.S.

En banc decision by the entire D.C. Circuit Court
of Appeals Followed
  • 8-2 against Abigail Alliance
  • Court holds that Alliances claimed right is not
    a fundamental right (such as a due process
    right), and therefore only subject to rational
    basis, not strict, scrutiny.
  • Burden for Alliance was thus to show that FDAs
    current policy bears no rational relationship to
    a legitimate state interest
  • Appeal (writ of certiorari) rejected by the U.S.
    Supreme Court. Case dead. The bottom line is that
    there is
  • No constitutional right of the terminally ill
    cancer patient to experimental drugs which have
    only completed Phase I testing and are awaiting
    FDA approval
  • Decision consistent with S. Ct. precedent

United States v. Rutherford 442 U.S. 544 (1979)
  • Terminally ill cancer patients and their spouses
    brought this action to enjoin the government from
    interfering with the interstate shipment and sale
    of Laetrile, a drug not approved under the FDCA.
  • Section 505 of the Act prohibits interstate
    distribution of any new drug unless an NDA is
    approved by Secy of HEW as supported by
    substantial evidence of the drugs safety and
  • This is still the law.
  • This case was the precedent the first decision,
    and the last decision, cited

Access to investigational drugs can differ, but
its not due to FDA
  • No real data to back up plaintiffs claims that
    access to investigational products is a big
    problem for cancer patients. Abigails oncologist
    was at Johns Hopkins, for instance.
  • There is a problem of availability for products
    from small biotech companies may not have
    enough of the product, or enough money to provide
    it for free outside of a clinical trial. That is
    not (just) FDAs problem.
  • Little literature on the difference in patient
    access to large molecule biologics from small
    companies versus getting drugs from big
    Pharmaceutical companies such as Pfizer

General results from access to drugs just out of
Phase I
  • Chance of dying from drug treatment 1/200
  • Chance of significant clinical response 2-4
  • These responses are virtually always partial
    responses of short duration
  • Chance of serious morbidity from treatment
  • NO ONE is ever cured by treatment with
    investigational drugs
  • IND Investigational New Drug. Approval required
    to allow a company to ship a drug. Thats why the
    court decisions all talk about interstate

New Drug Approval Today
  • Pre-clinical (Phase 0) testing in animals takes
    1-3 years, at least two species, to support
    preliminary work in humans
  • IND filed to begin investigation in humans. IND
    can be filed after Phase 0, I, or during Phase I
    or II. No rule except that preclinical testing
    must be completed first.
  • Phase I examines drug toxicity and
    pharmacology, MTD in 20-100 healthy human
  • Phase II drug tested in more patients with
    variety of diseases. Takes months-years
  • Phase III testing in hundreds-thousands with
    best, specific disease(s) drug most effective in
    from Phase II data. Trials takes years, can cost
    up to 60M
  • Results of 1-2 Phase III trials support NDA

Recent Changes to the Drug Approval Process
  • 1983 -FDA formalizes various exemptions to IND
    application process by allowing treatment and
    emergency use INDs to expand patient access to
    experimental drugs for those with no alternative
    therapy. Result of AIDS crisis.
  • Subpart E established variety of measures to
    expedite review and speed clinical trials,
    including use of only 1 study for approval and
    use of Phase IV post-marketing testing after
    allowing drug on market
  • Accelerated approval, including approval based on
    predicted benefit via use of surrogate endpoints
    in clinical trials (though must still prove
  • 1992 expedited review and parallel track
    program specific for HIV/AIDS therapies

Available FDA Mechanisms for Accessing Unapproved
  • Original language of section 505(i) of the FDCA
    was expanded in 1962 solely to authorize clinical
    trials designed to obtain safety and efficacy
    data sufficient to justify FDA approval of an NDA
  • FDCA never authorized/intended use of
    investigational drugs for ill patients outside of
    a clinical trial. But
  • Although FDA has not allowed commercialization
    of an unapproved new drug since 1938, it has
    often ignored the rule that investigational drugs
    cannot be used for treatment purposes
  • SO LONG AS there was a clinical trial ongoing and
    patients were not charged

Obtaining Investigational Drugs for Therapy
Whats Available?
  • Use for treatment, not just for clinical trial
  • General term is expanded access there is no
    single term or program. Some overlap.
  • An exception to general ban on commercial use of
    investigational drugs. Formalized in 561 of
    FDAMA in 1997, provides specific statutory
    authority for expanded access to investigational
  • Now are more than a dozen routes to access
    investigational drugs
  • FDA now considering changing rules, mostly to
    CLARIFY whats out there under what would be a
    new Subpart I to 21 C.F.R. 312
  • Would also clarify when you could charge for this

4 Basic Ways, Different Names
  • Enroll in a clinical trial sponsored by an
    institution or drug company
  • Obtain Compassionate exemption from physician
    participating in trial doctor requests drug from
    the company
  • Patient can write directly to the company to get
  • Physician can write to FDA to get approval for
    use by having doctor request either single
    patient or emergency use IND
  • Well elaborate on these and others

Investigational New Drug (IND) Access for Therapy
  • Individual Patient IND
  • Emergency Use IND
  • Treatment IND
  • Parallel Track IND
  • Group C Cancer Treatment IND
  • Open Label IND
  • Compassionate Use IND
  • Orphan Drug IND
  • Tropical Drug IND
  • Special Exception IND

Individual Patient IND
  • Single patient exception to allow use of drug
    outside of the protocol of the approved IND. FDA
    practice since 1962. Can be submitted by a drug
    manufacturer as an amendment to existing IND, or
    by physician or individual investigator on behalf
    of a patient
  • Legal Basis for this exception in Smith v.
    Shalala, (D.D.C. 1996) court held that FDA could
    allow a terminally ill cancer patient to get
    access to unapproved drugs undergoing
  • Formalized in 1997 under 561(b) of FDAMA any
    person may ask, through a physician, for access
    to an investigational drug for treatment of a
    serious disease or condition if meet 4 criteria
  • 1. there is no satisfactory therapeutic
    alternative available
  • 2. a protocol exists or will be submitted
  • 3. FDA determines that providing it will not
    interfere with clinical investigations to support
    NDA approval
  • 4. there is sufficient evidence of safety and
    effectiveness to support the use of the
    investigational drug
  • Note Would seem to eliminate anything without
    some Phase 2 data

Emergency Use IND
  • 561(a) of FDAMA codifies another basic FDA
  • Authorizes shipment of investigational drugs or
    devices for the treatment of a serious disease or
    condition in emergency situations
  • Exempt from prior IRB approval, as no time to do
  • MAY BE exempt for informed consent, such as in an
    ICU situation/unconscious patient, but usually
    informed consent is needed for emergency use IND
  • IRB approval must eventually be obtained, and an
    IND submitted afterwards
  • Physician requests this as well

Project BioShield Act of 2004
  • Expands emergency use
  • Adds 564 to FDCA to allow FDA to authorize use
    of an unapproved new drug during a declared
    domestic, military, or national security
  • Done twice by FDA at request of Pentagon, to
    allow emergency use of anthrax vaccine by
    military personnel

Treatment IND
  • 561(c) of FDAMA
  • Permits use of investigational drug under a
    treatment protocol (aka expanded access
    protocol for treatment of a serious or
    life-threatening disease
  • Grew out of peak of AIDS crisis. Final rules
    appeared in 1987
  • DOES allow sponsor to charge for this, but not
    more than is necessary to recoup costs
  • This has fallen into disuse when CMS and third
    party payers refused to reimburse for any drugs
    used under a treatment IND on the ground that it
    represented experimental use
  • Also fell into disuse when AIDS community used it
    to get unapproved meds that compromised efficacy
    of known medications. This is no longer a
    problem AIDS community now the first to insist
    that experimental meds with unproven efficacy be
    used inside of clinical trials because now have
    good meds

Parallel Track IND
  • Unlike others, this is not codified in CFR but
    was announced in Federal Register on May 21, 1990
  • Started in 1990 at impetus of NIH because of AIDS
  • Permits use of investigational drugs by people
    with AIDS and HIV-related diseases who are both
    unable to benefit from existing standard
    therapies AND unable to participate in ongoing
    clinical trials
  • BUT, an investigational new drug cannot be
    released into this program before patient
    enrollment in an FDA-approved Phase II clinical
    trial for that drug is initiated

Group C Cancer Treatment IND
  • Since 1976 NCI has furnished qualified physicians
    the most promising investigational drugs, called
    Group C drugs, to treat their patients outside of
    ANY clinical trial
  • These drugs appear in a master file submitted to
  • NCI includes on this list ONLY those drugs it
    concludes are likely to obtain NDA approval in
    near future. This is a big limitation
  • This is an informal program, also not codified
  • Appears in Memo of Understanding between FDA and
    NCI published in 1979
  • Under program, NCI asks FDA for permission to
    ship the investigational drug to the selected
  • Patients are not charged
  • These are virtually always only drugs NCI is
    developing themselves. You are NOT requesting
    this from a drug company

Open Label IND
  • Not codified
  • Usually just continuation of the treatment arm of
    a clinical trial that has concluded
  • Unlike others, do collect safety and efficacy
    data and report to FDA under the IND
  • Like a single patient IND but allows FDA to
    process requests for multiple individuals through
    a single general request from a drug sponsor

Compassionate Use IND
  • A broad, undefined term which sort of encompasses
    others. Not much difference from open label IND
  • Applies to situations in which the use of an
    investigational new drug for patient therapy does
    not fall within any other expanded access IND
  • FDA has VERY liberal view of this when there is a
    clear medical need
  • Again, big push for this arose out of AIDS crisis
    but now has broad applications in cardiology,
    neurology, etc

Orphan Drug IND
  • Prior to enactment of the Orphan Drug Act of 1983
    under Pres. Reagan, orphan drugs seldom proceeded
    from an IND to an approved NDA
  • This was thus a common mechanism
  • Much less so now, since companies now have real
    financial incentives to develop orphan drugs, and
    even greater incentive to see if there is a
    potential off-label use (e.g. Epogen)

Tropical Drug IND
  • FDA has long permitted drugs for tropical
    diseases to be the subject of clinical trials in
    the U.S. but until recently rarely approved NDAs
    on the grounds there was no need for such drugs
    in this country. Less so because of travel
  • Nevertheless, a tropical drug IND is pretty much
    a permanent state. Rarely go on to NDA

Special Exception IND
  • This comes from the sponsor, not the physician or
    the patient
  • When an individual is ineligible to enroll in a
    clinical trial of an investigational drug,
    sponsor can request that FDA permit a special
    exception from the protocol to permit excluded
    individual to receive treatment
  • Not in any FDA guidance or regulation, but it
    does happen. Data excluded from reporting.

Emergency Research
  • In 1996 FDA established regulations governing the
    narrow circumstance under which emergency
    clinical research may be conducted without
    informed consent, e.g. because of a
    life-threatening condition for which there is no
    available alternative and the patient is
  • 60 INDs submitted for this between 1996 and
    2006. No final rule yet

Importation of Investigational New Drugs for
Personal Use? Status
  • Again, originally a result of desperate AIDS and
    cancer patient efforts
  • Somewhat conflicting regulations FDA wont
    detain unapproved new drugs brought into U.S. for
    personal use at same time prohibiting them
    because of concerns about safety and fraud
  • FDA uses enforcement discretion to overlook so
    long as no intent to sell, and the use of the
    product is identified
  • A HUGE problem now with Internet, which FDA has
    not even begun to engage
  • Morphs over into the issue of importing approved
    drugs from Canada, which arose because of the
    cost of prescription drugs in this country.

Any holes in these programs for unapproved
  • Between the time FDA initially determined the NDA
    for Erbitux to be approvable and the time FDA
    approved the drug for marketing, the manufacturer
    received 8500 requests for compassionate use.
  • No data in FDA data bank on how often this was
  • No real data on how often patients cant get
    unapproved investigational drugs.
  • No real data on whether ANY of the previously
    described exemptions to IND regulations so that
    patients can access experimental drugs are too
  • In general, CDER/CBER/CDRH at FDA act on these
  • Any data from Methodist or M.D. Anderson ever
  • Patients always have final option of engaging in
    medical tourism

New proposals now being considered by FDA to
expand access to investigational drug and
biologic products
  • FDA now can authorize emergency use via
    telephone, fax, or email
  • Drug sponsor or physician obligated to later file
    a written submission complying with proposal, and
    to be added to IND file, within 5 days
  • Intermediate size populations where anticipate
    continuing protocol. Need some evidence of safety
    and efficacy first
  • New proposal will be much more specific about
    what charges may be covered
  • Not a minor issue example providing Provenge or
    other biologicals can easily cost a company
    50,000 or more/ patient. Biotech drug
    development differs.

What about unapproved biological drugs and
  • Covered by the Public Health Services Act (PHSA),
    not FDCA
  • Under control of CBER at FDA, not CDER
  • Examples Gene therapy, cancer vaccine products
  • General mechanisms are the same, all come under
    exemptions from IND requirements for
    investigational new drugs

Medical Devices
  • General approval routes
  • Expedited review
  • Product Development Protocols somewhat unique
    to devices
  • Investigational devices, and routes for
    exemptions to requirements

New Medical Device Approval
  • Route depends on the class (I, II, or III) of the
    medical device
  • Because approval requirements for marketing vary
    depending on the device class
  • Class I ? right to market
  • Class II? some to market, others via 510(k)
  • Class III?via 510(k) if substantially equivalent
    to predicate device on market before 1976 MDA to
    FDCA, otherwise?PMA
  • Standards for approval may be easier than for

Expedited Review
  • Exists for both drugs and devices to get them to
    market faster
  • Intended for drugs or devices to treat or
    diagnose a life-threatening or irreversibly
    debilitating disease or condition, and meet these
  • Device represents breakthrough technology
  • No approved alternative exists
  • Offers significant advantages over whats on the
  • Availability of the device in the best interests
    of the patient
  • Applications receive priority review, and are

Product Development Protocols (PDP)
  • A unique mechanism for devices, separate from PMA
    application, and no equivalent program exists for
    NDAs for drugs
  • Its a protocol to establish safety and
    effectiveness in humans based on a protocol
    (hypothesis, objectives, endpoints) BEFORE the
    study starts. Contains bench info, animal
    testing, maybe some data in humans
  • FDA experience with this is limited rarely used
  • Focus on established technologies spinal cages,
    pacemakers, new Pap technology

Investigational Devices and Patient Access to Same
  • For drugs there is the IND process
  • For devices there is the IDE process the
    Investigational Device Exemptions
  • Formal investigation of experimental devices
    aside, there are situations which arise where a
    patient will need a device which has not yet been

What Is An IDE?
  • A mechanism for conducting clinical safety and
    effectiveness evaluations for a device that has
    not yet been approved for marketing in the U.S.
    either a PMA
  • A way to get devices being tested to patients in
    need. For class III devices this will be before
    safety and efficacy data have been fully
    evaluated by FDA
  • Requirements for different exemptions vary

Purpose of an IDE
  • As with INDs for drugs, allows lawful shipment of
    an unapproved device across state lines for the
    purpose of conducting human clinical studies.
  • Its like an IND
  • And, what we are talking about is patient access
    before approval. Usually for class III devices
  • Encourages the development of useful devices
    consistent with public health, safety, and
    ethical standards
  • Sets procedures for conducting human clinical
    trials with new devices, and for access to
    devices outside of the trial as well.
  • There are requirements for an IDE application

IDE Application Requirements
  • Similar to those of IND IRB, consent forms,
    institutions, training manual, all investigators,
    investigational plan
  • Investigational plan purpose, protocol, risk
    analysis, device description, statistical
    analysis plan, monitoring process, how safety and
    efficacy will be measured
  • Statement re wont charge more than necessary to
    recover costs

Unlike Drugs, There Are Broad Exemptions from IDE
Requirements, aside from HDE
  • 510(k) cleared devices investigated in accordance
    with FDA-cleared indications for use
  • Veterinary devices
  • Devices intended and labeled solely for research
    with laboratory animals
  • Devices undergoing consumer preference testing
    which does not put subjects at risk and is not
    designed to determine safety or efficacy, i.e.
    device poses no risk
  • Custom devices for one patient UNLESS goal is to
    evaluate safety/efficacy for commercial
  • Diagnostic devices if test non-invasive,
    introduces no energy into the patient and is not
    used for diagnosis without confirmation by
    another established diagnostic procedure or test

Humanitarian Device Exemption (HDE)
  • Devices for the treatment or diagnosis of
    diseases affecting less than 4,000 patients in
    U.S. per year
  • Analogy to drug situation before passage of
    Orphan Drug Act
  • Criteria
  • Device not otherwise available
  • No alternative device
  • Exempt from showing it works (effectiveness
  • Only need safety evidence from non-clinical
  • Example twin-twin transfusion device

Threshold Requirements for FDA to Approve an HDE
  • Device will not expose patients to unreasonable
    or significant risk of illness or injury
  • Probable benefit outweighs the risk of injury or
  • Taking into account the probable risks and
    benefits of currently available devices or
    alternative forms of treatment

HDE Specifics
  • IRB approval required
  • Informed consent NOT required
  • Subject to GMPs
  • Cannot make a profit
  • 75 day review by FDA
  • HDE approvals by FDA 2001-2004 28
  • Examples approved fetal bladder stent, heart
    value, bladder stimulation device
  • For these products there was limited clinical
    information available, mostly bench/animal/cadaver
    testing, as well as knowledge about the natural
    history of the disease without the device

Other IDE Types
  • Full IDE for a Significant Risk Device
  • Abbreviated IDE for a non-significant risk device
  • Treatment Use IDE
  • Emergency Use IDE
  • Compassionate Use IDE
  • Continued Access IDE
  • Clearly, similar to those for access to
    investigational drugs which are part of INDs

Significant Risk Device (SRD)
  • Investigational device that presents potential
    for serious risk to health, safety or welfare of
  • Is an implant
  • Is intended to support or sustain life
  • Is of substantial importance in diagnosing,
    curing, mitigating, or treating disease, OR
  • Otherwise presents potential serious risk

Full IDE for SRD
  • Requires both IRB and FDA approval prior to use
    in patient
  • Sponsor or manufacturer makes initial
    determination whether a device is SRD or NSRD
    reviewing IRB must concur
  • FDA does have some guidance documents on this
    available at

Abbreviated IDE
  • For NSRDs
  • Study deemed approved without need for actual FDA
  • Institutional IRB serves as surrogate for FDA
  • More efficient fewer records
  • FDA typically not aware of the existence of these
    because no submission to FDA
  • If something goes horribly wrong or someone
    submits a marketing application, FDA will find out

Treatment Use IDE
  • Occurs during a ongoing clinical trial
  • Why? Permits use of promising new devices for
    desperately ill patients before clinical trials
    are complete and marketing authorized
  • When investigators figure out that the device
    they are studying really works!
  • Generates additional safety/efficacy data
  • Requires application or call to FDA prior to FDA
    oking it
  • Rarely used. Example early use of the
    Intra-aortic balloon pump

Treatment Use ID - Criteria
  • Device intended to treat or diagnose a serious or
    immediately life-threatening disease/condition
  • No comparable or satisfactory alternate
  • Device is or was the subject of an approved IDE
    for the SAME use
  • Sponsor is actively planning or pursuing
    marketing application

Emergency Use IDE
  • Timing before or after initiation of study
  • Allows use of an investigational device in a
    manner consistent with the approved
    investigational plan or by a non-investigator
  • No prior FDA approval required, but use must be
    reported to FDA w/in 5 days
  • Cannot be used multiple times
  • Key point can occur before study starts, so
    different from treatment IDE
  • This stuff shows up on TV all the time
  • Ultimately need to contact relevant section at

Emergency Use IDE Criteria
  • Serious or life-threatening condition requiring
    immediate treatment
  • No acceptable alternative treatment
  • No time to obtain prior FDA approval
  • Physician expected to take as many patient
    protection steps as possible (e.g. informed
    consent, authorization of IDE sponsor, IRB
    approval if possible

Compassionate Use IDE
  • Timing during a clinical study
  • Allows off-protocol use of investigational device
    by a small number of patients for whom device may
    provide benefit for a serious disease or
  • Requires prior FDA approval of an IDE supplement
    and submission of follow-up information on
    safety, etc after treatment
  • Note not just for one patient, as with Emergency
    Use IDE

Continued Access IDE
  • Timing after completion of study
  • What it is continued enrollment of subjects
    pending submission of marketing application
  • Must be public health need for device
  • Preliminary evidence of likely effectiveness and
    safety concerns
  • Requires FDA approval of IDE supplement
  • This is a pretty good idea actually, as are most
    of the IDE regulations. Patients have lots of

Emergency Use of Unapproved Medical Devices by
Physicians A Good Idea?
  • Should FDA assert no authority?
  • Arguments Pro
  • FDA can always review post-facto and has
    discretion whether to discipline or not
  • Essential if truly life and death situation
  • Can always get informed consent in advance, or
    after it works if patient survives
  • Will curtail innovation without it\
  • Note FDA does NOT regulate the practice of

Against Emergency Use of Unapproved Medical
Devices by Physicians A Bad Idea? Arguments
  • Emergencies rarely unanticipated
  • Hospital protocols and civil liability of docs
    not a good check on behavior, particularly
    renegade surgeons
  • If its built someone will look for an excuse to
    use it
  • Just because someone is going to die does not
    justify using something with no known safety or
    effectiveness record
  • Physicians cant police themselves
  • Rutherford case patients cant just ask for any
    therapy it must be approved first
  • The first artificial heart (Karp) and heart
    transplant in U.S. (Cooley) both resulted in
    litigation. Worth it?

Finally, some data CDRH IDE Statistics 2006-2007
  • ODE reviewed 400 pre-IDEs
  • 100 of ODE decisions on original IDEs issued
    within 30 days
  • 74 of original IDEs accepted for substantive
    review approved on first review cycle
  • 4300 IDE supplements submitted average review
    time 19 days
  • Point as with INDs for drugs, FDA very
    accommodating and encourages this stuff
  • Data on exemptions not much, as records kept by
    each section of CDRH and (incredibly) its not
    computerized. Consensus is that process is

What About Reimbursement?
  • Under interagency agreement with CMS, FDA places
    all IDEs it approves in Category A or B
  • Category A experimental novel class III
    devices for which safety/efficacy not established
  • Category B devices which have some
    safety/efficacy data, typically refinements of
    existing products. Eligible for CMS coverage
    under reasonable and necessary standard
  • January 2005 CMD began covering routine costs of
    Category A
  • IDE cover letter should thus be directed at BOTH
    FDA and CMS

How about Dr. Kevorkian?
  • His death device was unapproved by FDA
  • Never submitted an IDE
  • FDA didnt go after him. Drugs he used were
    approved but used off-label in a criminal manner
    violating state law (Michigan)

A final comment about device-related
death/serious injury
  • Device manufacturer/institution needs to know
    about these events in 3 ways under rubric of
    when reasonably known
  • If knew or discovered on its own
  • If was told by physician, hospital or another
    hospital, or a consumer
  • IF COULD HAVE FOUND OUT that device may have
    caused or contributed to death or serious injury

FDA Guidance for Physicians/Surgeons
  • Emergency Use Authorization of Medical Products
  • July 2007
  • Available at http//
  • emergencyuse.html

Final Slide Dealing with FDA
  • Find out which Center youre dealing with (e.g.
    drugs, devices, biologics)
  • Find out which division within the Center has
    your medical product
  • Find out who the Project Manager is much better
    than dealing with the assigned Medical Officer
  • Never lose your temper