Science, politics, culture: the challenges
for medical technology and its regulation
Kenneth H. Keller
School of Advanced International Studies
The Johns Hopkins University
Bologna, Italy
The readings: some themes
• Regulation: matching institutional structure to the
dynamics of technological innovation
• Cost and benefit: the economist’s challenge
• Risk and benefit: the media and/or society
• “Narratives”: symbol versus substance
• The diminishing deference to expertise in an
information age
• The contrast between drugs and devices
EU and US contrasts: I
• Political organization
– EU- Relative trust of government; delegation of authority;
executive power
– US- Suspicion of experts; populist government; legislative
control
• Social/economic factors
– EU- Flatter income distribution; social safety net;
identification with “place”; universal health insurance
coverage; higher taxes.
– US- Enormous wealth variation; non-uniform medical
practice system; serious health insurance gaps; high
expectations.
EU and US contrasts: II
• Cultural factors
– EU- Strong antipathy to genetic manipulation (food more than
pharmaceuticals), BUT openness to other medical technologies.
– US- More open to genetic manipulation than to medical
devices.
• Religious factors
– EU- Primarily secular societies; religion not a strong factor in
policy or bioethical arguments.
– US- Highly religious society; formal separation of church and
state, but major factor in policy debates.
EU and US contrasts: III
• Privacy
– EU- a “human dignity” issue; vis-a-vis other private parties,
NOT government. Thus, consistent, comprehensive,
government-enforced regulation.
– US- a liability, “rights” issue; vis-à-vis government.
Patchwork of regulations, difficulty of enforcement.
• Freedom of Information
– EU- Very low priority; very limited. A problem in creating
“sunshine” environment.
– US- Frequently a concern to government and private
entities, but a major element in “checks and balances”.
Civic Epistemologies*
United States
Contentious
Britain
Communitarian
Germany
Consensus-seeking
Styles of public
knowledge-making
Pluralistic, interest
based
Embodied,
service based
Corporatist,
institution based
Public accountability (trust basis)
Assumptions of
distrust; Legal
Assumptions of
trust; Relational
Assumption of trust;
Role-based
Demonstration
(practices)
Sociotechnical
experiments
Empirical science
Expert rationality
Expertise
Professional skills
Experience
Training, skills,
experience
Visibility of expert
bodies
Transparent
Variable
Nontransparent
*Jasanoff, S. Designs on Nature: Science & Democracy in Europe & the U.S. (Princeton U. Press 2005)
Current Medical Technology Policy Issues
• Regulatory mechanisms for device development (the failure of
the drug model).
• Criteria for clinical adoption of new technologies.
• Clinical cost control and support of research/training.
• Promoting multidisciplinary research.
• Meeting global needs.
The changing context
 New fields; new interactions
 Confluence of research and development
 Rising health care costs
 Health concerns in the developing world
 Effect and affect: the social and human
dimensions of medical technology
Effect and affect: the social and
human dimensions

Public policy issues (effect):





Personal values and beliefs (affect):




Distributional justice and priority setting.
Quality of life and evidence of value.
Privacy.
The threat of adverse selection.
Human identity and aversion to “technical invasion.”
Technology as symbol; religious beliefs and core values.
Risk assessment vs. risk perception.
Personal empowerment.
“Rational” societal investment in medical treatment
Disease A
$
Disease B
People-years of extended life
What is the criterion for “acceptable” risk?
Economist’s preference
Socially tolerable
Personally acceptable
(depends)
94%
96%
98%
Reliability (% device survival/yr)
100%
Effectiveness of organ transplants
Average years of life after transplant
Age-based actuarial prediction
1
With transplant
Without transplant
0
Severity of disease
What a difference a valve makes
Graph courtesy of F Schoen
Courtesy Dr Fred Schoenfeld, Brigham
The price of risk reduction
Relative cost
103
100
Iteration, experience
10
.0001
.001
.01
Probability of device failure
0.1
What is a medical device? FDA
classifications
» Pharmaceuticals
» Biologics
» Medical devices
What is a Medical Device?
“an instrument, apparatus, implement, machine, contrivance,
implant, in vitro reagent…which:
•Is recognized in the official National Formulary, or the U.S.
Pharmacopoeia, or any supplement to them,
•Is intended for use in the diagnosis of disease or other
conditions, or in the cure, mitigation, treatment, or prevention
of disease, in man or other animals, or
•Is intended to affect the structure or any function of the body
… and which does not achieve any of its purposes through
chemical action within or on the body…and which is not
dependent upon being metabolized for the achievement of
any of its primary intended purposes.”
Medical Devices
Combination products: a challenge to
regulation*
Def’n: Products that involve some combination of device, drug, and/or “biologic”.


Tissue engineering

Tissue scaffolds (skin, nerve regeneration)

Hybrid artificial organs (pancreas, liver)

Cloned organs
Drug delivery systems

Drug-eluting stents

Site-specific chemotherapeutic particles

“Intelligent” sensors
* Regulators abhor an ambiguity
Medical Device Classes
•
Class I - Minimal potential for harm
– Subject only to general controls
– Exempt from premarket notification
– Some exempt from GMP except for record keeping and complaint files.
•
Class II - Held to a higher level of assurance than Class I
– Subject to general and special controls (labeling, performance standards,
post-market surveillance)
– Require 510(k) premarket notification unless exempt
•
Class III - Highest risk, manufacturing controls insufficient to assure
safety and effectiveness, the device is life-sustaining, important in
preventing impairment of human health, or presents a potential
unreasonable risk of illness or injury
– Subject to general and special controls and
– Require Premarket Approval Application (PMA) unless a pre-amendment
device
FDA Perspective
Safe experimentation
Premarket safety
Premarket effectiveness
Research Inspection
Truthful promotion
Adverse Event Reporting
Postmarket studies
Manufacturing Inspection
Recall
Notification
The Gatekeeper Approach
Responsible party
Decision Driver
Device Status
Comment
NIH
Research
Experimental
Hypothesis/disease driven
FDA
Development
Experimental
“Safe and effective”
CMS/Insurers
Payment
Clinical
“Reasonable & necessary”
Hospital/Physician
Clinical use
Clinical
Judgment or evidence?
Patient
Quality of life
Private property
Patients, docs, lawyers
??
None
??
Losing explant data
What do “safety” and “efficacy”
mean?
• Emphasis in U.S. on clinical outcome (the “gold standard”:
double-blind statistically significant studies)
–
In contrast, the CE Mark (Conformité Européen) requires that the device
achieve its intended purpose as designated by the manufacturer
• Distinction between “efficacy” and “effectiveness”
• How safe is safe?
– In Europe, “any risks associated with its use are acceptable when
weighed against the benefits to the patient.
EU Device Regulation & Harmonization
• The CE Mark (Conformité Européne) requires that device:
(i)
Does not compromise the clinical condition or safety of the patient;
(ii) Achieves its intended purpose as designated by the manufacturer;
(iii) Any risks associated with its use are acceptable when weighed
against the benefits to the patient.
• Concept of Competent Authorities (national entities).
• Concept of Notified Bodies (private entities).
Technical feedback: closing the loop
•
Mfrs have legal responsibility for “device vigilance” but physicians are
major source of “incident” reporting.
•
Requirement to report incidents to relevant Competent Authority (CA);
CA responsible for notifying other CAs.
•
Limited distribution of information:
– Dialogue with manufacturer
– Notice to users only when serious and necessary
– No public availability of data or data base
•
EUDAMED: European Database on Medical Devices
Why “drug model” (gatekeeper) regulation
fails in medical technology development
 Iterative nature of technical systems development
 The technology learning curve
 Limitations on “drug model” testing protocols:



Limited data collection possibilities
Scaling constraints
Impracticality of double-blind studies
 Small size of medical technology companies
 Small size of medical technology markets
 Sometimes not suitable for general clinical practice
Unintended consequences of
gatekeeper regulation
 Reduced innovation; the siren call of “substantial
equivalence”
 Sub-optimal designs; avoiding design revision
 Failure of small, innovative firms; the “burn rate”
 Reduced competition
 Absence of clinical monitoring of effectiveness and
design improvement
Is clinical testing always the “gold standard”?
 The strengths of clinical testing:
• Sensitivity to systems effects
• Clinical outcome orientation
 The weaknesses of clinical testing:
• Insensitivity as early warning system
• Lack of information/guidance on mechanisms
• De-emphasis on extrapolation
Registries: Premarket Perspective
Potential Applications
 Provide data to support development & design of clinical
trials
 Provide historical comparator data (if rigorous)
 Enhance safety assessments via broader analysis of
adverse events
 Provide access to product (outside of IDE trial)
 Expedite approval of device modifications or labeling
Registries: Postmarket Perspective
Potential Applications
– Provide surveillance for “real-world” events
– Assess generalizability of new technologies
– Expedite time to market with reliable postmarket data
– Provide vehicle for Post-approval Studies (PAS)
– Promote evidence development for CMS’ national
coverage decisions (NCDs)
Policy solution directions

Long term:
– Recognition that medical devices and technologies can never be
entirely experimental nor entirely clinical
– De-emphasis on “gatekeeper” approaches in favor of continuous
regulation and monitoring that leads to early introduction, but
ongoing control of clinical setting and data gathering

Near term:
– Pilot programs in conditional coverage
– Financing of medical device registries and implant retrieval
Some final questions
• How risk averse should we be?
• Are we asking the right questions about benefit?
• How could we alter the system and still protect the
public?
The International Challenges
 Autonomy and bureaucracy
 The temptations of trade restriction
 Standardizing data collection and evaluation
 Institutionalizing scientific consensus
 Harmonizing regulatory approaches
 Contrasting patterns of litigiousness
 Freedom of information and clinical monitoring
 Social and religious values