Transcript Power Point Presentation - Kristine Shields MSN, DrPH

Research Study:
The Participation of Pregnant Women in
Clinical Research: Implications for Practice
within the U.S. Pharmaceutical Industry
University of North Carolina
Gillings School of Global Public Health
Kristine Shields MSN, DrPH
2012
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Problem
Millenium Development Goal #5:
Reduce Maternal Mortality
1.7 Million Pregnant Women
2 die
every day
600,000 have
complications
> 1 million are
prescribed drugs
See References slide
2
Problem
80%
See References slide
3
Policy Window Opens
FDA Draft Guidance:
Pregnant Women in Clinical
Trials: Scientific and Ethical
Considerations
4
Policy Window Theory of Change
Kingdon: Agendas, Alternatives, and Public Policies
5
Kingdon recommends:
Special studies of the issue

Indicators of the
existence and
magnitude of issue
 Promotion of
constituent feedback

Quantitative
methodology

Qualitative
methodology
Kingdon: Agendas, Alternatives, and Public Policies
6
Quantitative Study
ClinicalTrials.gov
 U.S. industry-sponsored Phase IV studies
 Exclusion criteria

7
Quantitative Study Results
555
Studies
5
Enrollment limited
to pregnant women
452
Potentially
include
301
Excluded
2
Not
Excluded
149
Unknown
84
No Response
Confirmed criteria = 368 studies
Total excluding =
65
Responded
46
Excluded
98
Appropriately
excluded*
347 (94%)
Total not excluding = 21 (6%)
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Not
Excluded
* Pregnant women were excluded because the drug was in FDA Category D or X, or the age
or topic (menopause, contraception, lactation) prohibited pregnancy.
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Qualitative Study
Key Informant interviews:
 Pharma companies
 Big Pharma……………5
 Biotech…………….......3
 Industry attorneys………..3
 IRBs……………………….3
 PhRMA association……...1
 FDA………………………..1
(N = 16)
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Qualitative Study Results
Key Concerns
Key Potential Solutions
Causing harm to the fetus;
scientific concerns
Study design; scientific advances in modeling and
animal testing; Phase III & post-marketing studies
Litigation
Guidance/regulation; informed consent; indemnification; improved awareness of issue in public domain
Enrollment concerns
Pk testing on small numbers; partnerships with OPRU
/obstetrical community, data from multiple sources
Impact on initial approval
Post-approval studies
Lack of regulatory agency
support, regulations
FDA guidance document, international harmonization
Business concerns
Define market; conduct post-approval studies; devise
incentives and protections
Lack of experience
Collaboration, best practices, innovation, science
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Plan for Change: Problem
Problem
Awareness of
the issue as a
problem
Policies
Propose
potential
solutions for
consideration
and debate
Politics
Influence
within
company,
within
industry,
within country
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Plan for Change in Problem Stream
Solution:
 Communicate the extent
of pregnant women’s
exclusion from clinical
research and why this is
a problem
 Increase awareness of
the 'issue as a problem'
among individuals in
industry, IRBs, and
industry associations
Intervention:
 Publication on
quantitative results in
peer-reviewed scientific
literature

White Paper distribution
to industry associations
(PhRMA and BIO), to
key informants, and to
colleagues in the
industry
12
Plan for Change: Policies
Problem
Awareness of
the issue as a
problem
Policies
Propose
potential
solutions for
consideration
and debate
Politics
Influence
within
company,
within
industry,
within country
13
Plan for Change in Policy Stream
Intervention:
Solution:
 White Paper to FDA,
 Provision of potential
PhRMA, BIO, and
solutions for industry
pharmaceutical and
consideration in
biotech companies (via
guidance responses &
key informants)
internal policies
 Present study findings at
 Industry perspective
FDA hearing, if
included in discussion of
applicable
the issue
 Participate in drafting
 Provision of potential
response to FDA’s call
solutions for Merck's
for comment
draft response
14
Plan for Change: Politics
Problem
Awareness of
the issue as a
problem
Policies
Propose
potential
solutions for
consideration
and debate
Politics
Influence
within
company,
within
industry,
within country
15
Plan for Change in Political Stream
Solution:
Intervention:
 Personal influence on
 Continue involvement in
internal deliberations on
issue
issue
 Continue involvement in
 Issue remains in public
other industry and nonand professional
industry organizations
consciousness;
 Additional publications
 Continued advocacy for
and presentations
increased evidenceprovide information for
based treatment for
advocates to influence
pregnant women
legislators, legislation
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Impact of Deliverables
Problem
Stream
Publication(s)
White
Paper
Presentations
Involvement
Policy
Stream
√
Political
Stream
√
√
√
√
√
√
√
√
√
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The purpose of this study was to:
1.
2.
3.
4.
Quantify the problem and
Isolate and barriers to and
opportunities for change
In order to influence policy
That will improve maternal
health
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Questions?
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REFERENCES





[i]Daniel I et al. Magnitude of maternal morbidity during labor and
delivery: United States, 1993-1997. American Journal of Public
Health 2003; 93(4):631-4.
[ii] Heron M et al. Deaths: Final data for 2006, National Vital
Statistics Reports 2009; 57(14):116, available at
http://www.cdc.gov/nchs/data/nvsr/nvsr57/nvsr57_14.pdf.
[iii] Andrade SE et al. Prescription drug use in pregnancy.
American Journal of Obstetrics and Gynecology 2004; 191:398407.
[iv] Glover DD et al., Prescription, over-the-counter, and herbal
medicine use in a rural obstetric population. American Journal of
Obstetrics & Gynecology 2003; 188:1039-1041.
[v] Lo WY & Friedman JM. Teratogenicity of recently introduced
medication in human pregnancy. Obstetrics & Gynecology 2002;
100:465-473.
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Back-up Slides
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Has this been done before?

Precedent:
Pediatric Exclusivity Provision, FDAMA (1997)
 Best Pharmaceuticals for Children Act (2002)
 Pediatric Research Equity Act (2003)


Results:
increase in pediatric drug testing
 changes in labeling regarding dosing and pk,
safety, lack of efficacy, etc.

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How will study results promote a
Plan for Change?
Leadership is a “process of influencing
others to understand and agree about
what needs to be done and how to do it,
and the process of facilitating individual
and collective efforts to accomplish
shared objectives.”
Gary Yukl, 2006
23
Ethics

Arguments for and against inclusion
Beneficence/Non-maleficence
 Justice
 Autonomy/Respect
 Ethic of Care
 Stakeholder theory

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Public Health Advocacy

Every public health decision is a political
decision.
 Public health historically fails to close the sale
with policy-makers and politicians.
 Public health officials tend to be scientists at
heart with an innate aversion to politics.
 We must leverage status as public health
leaders to get the political system working for
public health - and not against it.
Risa Lavizzo-Mourey, President and CEO, RWJF 2008
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Limitations: Qualitative
Limited to U.S. Phase IV clinical trials – not generalizable
ex-US.
 Phase IV is proxy for Phase II and III trials because I
cannot evaluate if it would be appropriate for pregnant
women to be included in Phase II or III studies from the
data source or in the public domain.
 Some of the inclusion and exclusion criteria listed may
not mention pregnancy or pregnancy potential. Cannot
assume that if pregnancy is not mentioned as an exclusion
criterion then pregnant women can be included as study
subjects. In order to validate the initial findings, any
protocols that do not mention pregnancy or pregnancy
prevention per se will be contacted.
 However, this still may not address de facto exclusion, i.e.
the "inadvertent" failure to recruit pregnant women.

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Limitations: Qualitative



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Participants interviewed may or may not represent the perspectives of
other companies and organizations or a consensus on the subject.
In telephone interviews physical proximity, visual clues such as body
language and facial expressions are lost.
Convenience sample based on my contacts in the industry and related
organizations. Most, but not all, participants will be known to have
worked on pregnancy-related issues which will improve their ability to
discuss the issue in depth but this may introduce bias as they may not
represent the thinking of the industry at large.
In the interview data analysis, findings could be subject to other
interpretations that may differ from my interpretation. Using
evidence from inside and outside industry will add to the validity of the
findings by using triangulation –to see if similar themes are identified.
As someone with background in women's health, I bring knowledge but
also certain biases to this study. I acknowledge that I agree with
proponents who seek a more rational and inclusive policy toward
pregnant women in research studies. And I acknowledge that, while I will
strive to maintain objectivity in the data collection and analysis, my
biases may influence my findings.
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