1. The Global Relationship:
Corporate Social Responsibility (CSR),
Applied Research Ethics,
&
the Clinical Research Enterprise
Linda Strause, Ph.D Matthew Whalen, Ph.D
Vical Incorporated IMPACT LLC
Global Clinical Trials
Philadelphia, PA, USA
September 15-16, 2011

2. The ‘Grand Bargain’ / Social Contract
“What we are witnessing is the
unraveling of a ‘grand bargain’ between
the pharmaceutical industry and
society … a complex, implicit social
contract. … As the twenty-first century
begins… this grand bargain is in tatters
and public mistrust and resentment of
the industry run feverishly high. … The
time has come to renegotiate [it].’”
Dr. Greg Koski
Ethics and the Pharmaceutical Industry (2005)

3. Public Mistrust

4. the ‘Triple’ bottom line
“In practice, business sustainability consists of
managing the ‘triple bottom line’ … decision-making
that takes into consideration financial, social, and
environmental risks, obligations and opportunities.
Sustainable businesses survive over the long term
because they are intimately connected to healthy
economic, social and environmental systems.”
Bertels S, Papania L, Papania D.
Embedding Sustainability in Organizational
Culture: A Systematic Review of the Body of
Knowledge. Network for Business Sustainability

5. So, being socially responsible is …
 “Growing jobs and clients/customers” by
 Aligning “Private Profits” &“Public [Health]
Interests”
 Renegotiating the “grand bargain / social
contract,” explicitly
 Using a “triple bottom line” of Sustainability
(economic, social, and environmental)

6. AGENDA
 Overview of Corporate Social Responsibility
 Business Ethics in the 21st Century
 Applied Research Ethics
 Protection of human subjects
 Ethical decision-making: subjects facing life threatening
illnesses
 Enterprise Sustainability, Governance
 Clinical Research Sustainability, Feasibility of Studies
 Accountability/Liability and Access/Transparency

7. Between the Research Enterprise & Society
Economic
Public Health Development
FAIR
SUSTAINABLE
FEASIBLE VIABLE
Innovation

8. Corporate Social Responsibility
A brief Overview
“According to our [global Pharma industry]
experts, CSR is
not a “nice to have” addition
to company policies,
but an integral part of
today’s overall business strategy.”
Robin Robinson, “CSR gets a Makeover,” PharmaVOICE
(June, 2011), Page 14

9. CSR in the 21st Century
CSR has evolved to focus on:
s Business Ethics
s Enterprise Sustainability
s Corporate Governance
….on a global scale, given
the international nature
of business.

10. To ‘translate’ CSR to Clinical Research
 where Applied Research Ethics is Business Ethics
 where Enterprise Sustainability takes into account
new research paradigms, public health-centric
priorities, and the feasibility (including viability) of
the studies themselves
 where Corporate Governance is synonymous with
Accountability and Transparency

11. Reinforcement:
The EU’s Single Market Act & CSR
Due to be passed into law by the end of 2011, it is
widely expected to contain some form of mandatory
CSR requirement for medium and large size
companies; and, “the Commission will also adopt a
Communication on corporate social responsibility
(CSR) -- a wider concept than social business -- which
encourages all businesses to pursue actions with
social or environmental objectives as part of their daily
activities.”
COMMUNICATION FROM THE COMMISSION TO THE EUROPEAN
PARLIAMENT, THE COUNCIL, THE ECONOMIC AND SOCIAL
COMMITTEE AND THE COMMITTEE OF THE REGIONS
Single Market Act Twelve levers to boost growth and strengthen
confidence "Working together to create new growth” § 2.8 Social Entrepreneurship

12. Reinforcement:
The U.N. Global Compact and CSR
The 10 principles of the Compact with international
business focus on:
s Human Rights (i.e., abuses, collective
bargaining, child labor, discrimination);
s Environment (i.e., challenges,
responsibilities, and ‘friendly’ technologies);
and,
s Transparency (anti-corruption in all its forms,
including extortion and bribery).
unglobalimpact.org

13. Applied Research Ethics

14. Scientific Advances … ramifications
“As science speeds ahead, it often
pushes the edges of society’s
readiness to cope with its
consequences… Increasingly, research
creates possibilities before the
accompanying ethical, social, and legal
ramifications have been resolved.”
Editor, “Science on the Ethical Frontier” series
Washington (DC) Post, 1998 – 1999

15. Applied Research Ethics:
8 Principles for International Trials
2. Social and Scientific Value
3. Scientific Validity
4. Fair Subject Selection
5. Favorable Risk-Benefit Ratio
6. Independent Review
7. Informed Consent
8. Respect for Enrolled Subjects
9. Community Perspective
NIH’s Center for Bioethics

16. Applied Research Ethics:
Social Value & Community Perspective
 “Social Value” relates to the public health priorities of a
country and “varied disease burdens.”
 some regulatory bodies deny studies with no long-term
benefit to its citizens,
 drug developers need to work with governments to
identify how studies will aid both trial participants and,
eventually, the wider population.
 “Community Perspective” is “sharing the benefits” not just
the risks;
 value of the research to the country
 if the results include approval, will that therapy actually
be available to patients in the country.

17. Applied Research Ethics:
Scientific Validity & Fair Subject Selection
 Scientific Validity relates to
 Design of the study, e.g., placebo use
 Study Product in comparison/contrast to approved and
available therapies
 ‘Mechanisms of action’;
 Fair subject selection and the principle of “justice” relates to
 Fairness in distribution and what is deserved
 Distribution of benefit and risk:
1. to each person an equal share,
2. to each person according to individual need,
3. to each person according to individual effort,
4. to each person according to societal contribution,
5. to each person according to merit.

18. Applied Research Ethics:
Risk/Benefit Ratio & Respect for Subjects
 Balancing the potential risk to the potential benefit:
 Equipoise provides the ethical basis for clinical research
involving patients assigned to different treatment arms.
 Clinical equipoise means that there is genuine uncertainty
over whether a treatment will be beneficial.
 While ensuring that the autonomy of the subject is protected:
 Vulnerable populations
 Real understanding of informed consent process,
therapeutic misconception, and recruitment/selection

19. Applied Research Ethics:
Independent Review & Informed Consent
 Nuremburg gave us the Institutional Review Boards:
 Responsibilities (and roles) of the sponsor of the
research, investigator conducting the research, and the
ECs/IRBs overseeing protecting the rights and welfare of
research participants
 Understanding that informed consent is more than a piece
of paper, it is a process:
 societal needs v. the individual
 evaluable data v. therapy
 therapeutic misconception (“white coat syndrome”)

20. Applied Research Ethics:
Therapeutic misconception
“…was present in 70% of respondents,
who expected to receive better care and
ignored the consequence of randomisation
and treatment comparisons. This was
positively associated with the acuteness
and severity of the disease.”
J Med Ethics, 2008 Sep;34(9):e16.
“Informed consent in clinical research in France:
assessment and factors associated with therapeutic misconception.”
Durand-Zaleski IS, et al

21. Applied Research Ethics:
Coercion
“… [A] patient suffering from a life-
threatening disease may feel as though
she has little choice regarding
treatment. Physicians should be aware
of how vulnerable patients may be to
the coercive influence of unrealistic
hope, especially those suffering from
chronic, life-threatening disorders.”
Berg, Applebaum, Lidz, and Parker, Informed
Consent: Legal Theory and Clinical Practice. 2001.

22. Applied Research Ethics:
Coercion
In a study of terminally ill cancer patients who
enrolled in a Phase I study.
 Do you feel pressure to enroll in the study?
 Over 80% report yes.
 How much pressure do you feel from?
 Family 9%
 Researchers 7%
 Growing Cancer 75%
IS THIS COERCION?
2011 The Hastings Center: Unrealistic Optimism
in Early-Phase Oncology Trials, Jansen, et.al.

23. Applied Research Ethics:
Coercion
In a study of terminally ill cancer patients who
enrolled in a Phase I study.
 Do you feel pressure to enroll in the study?
 Over 80% report yes.
 How much pressure do you feel from?
 Family 9%
 Researchers 7%
 Growing Cancer 75% since cancer
This is NOT coercion is
generating the pressure
2011 The Hastings Center: Unrealistic Optimism
in Early-Phase Oncology Trials, Jansen, et.al.

24. Ethical Perspective
Therapeutic misconception
Two Cousins, Two Paths Thomas McLaughlin, left, was given a promising
experimental drug to treat his lethal skin cancer in a medical trial; Brandon Ryan
had to go without it.
10Sep13: Monica Almeida/The New York
Times, Drug Trial Stirs Debate on Rules – Melanoma

25. Applied Research Ethics:
a Balancing Act
Patients seek new drugs for
hope of personal benefit
New drugs need testing in
clinical trials

26. Applied Research Ethics:
a Balancing Act
 What risk could be worse than the risk of
death?
 New drugs could have toxicities that involve or
increase the risk of suffering and pain, and
acceleration of death.
“There are things worse than death – being made to
die faster, being made to die more miserably, or
having one’s dying prolonged … with no increase in
quality of life.” Bioethicist Arthur Caplan, 2007

27. Applied Research Ethics:
HOPE
 HOPE:
 Understanding and innovation inspire HOPE
 Does ‘therapeutic misconception’ abolish HOPE
 “You can take away my misconceptions, but
you can’t take away my HOPE”.
-- Judy Olson, Research Participant
Is HOPE a deterrent to clinical trial
participation?
-- Personal Story

28. Applied Research Ethics:
Situational Ethics
“Ethics is the study of reasons people give for
the behavioral choices they make. Ethics tries
to get people to reflect on their behavior and
how they justify that behavior, not just choosing
what to do but offering a rationale for what
you’re going to do”
(Dr. Baasten)
The ethical decisions that we make are
more often NOT between Good and Bad
but between
Good and Good.

29. Enterprise Sustainability
(including Feasibility of Studies)
&
Governance

30. Enterprise Sustainability
“Paradigm-breaking business …”
“… transitions to sustainability may involve the need for
paradigm-breaking business models or approaches.”
Perhaps like …
s New Regulatory Science
s Systems thinking/Holistic approach (e.g., MIT)
s Alternative/Complimentary Medicine research
s “Virtual Physiologic Human” (e.g., Univ. of Nottingham +)
s “Culture of Safety”
s Collaborations in research (e.g., PhRMA and academic Research Centers)
s Translational Science (e.g., NCATS -- government and industry)
s “Point-of-Care” Clinical Trials
s Adaptive Trial Design (especially Phases II, II/III)

31. Enterprise Sustainability
Public Health-centric Prioritizing
including competing for scarce resources
In addition to “varied disease burdens” and “shared
benefits:”
 “Participatory [or patient-centric] Medicine”
 The research enterprise as critical to Economic
Development in ‘developing’ countries
 The research enterprise’s continuing central role in
Economic Development in ‘developed’ countries

32. Sustainability and the Feasibility of Studies
Standards, Experience, Priorities as CSR
s Record of abiding by International Standards,
including any history of ethical abuses and
established track-record of robustness
of review (regulatory/ethics) processes
s Determining what exists as a Standard of Care
s Correlation of protocol with overall as well as
disease state-specific research experience
s Prioritized Populations based on country-
specific health authorities and objectives
s Adequacy of safety profiles including any comparators
and rescue medications

33. Sustainability and the Feasibility of Studies
What Sponsors look for in CROs
and being socially responsible
5. therapeutic expertise
6. cost feasibility/viability
7. a global footprint
8. clinical research associates quality; and,
9. upfront contingency planning … that is, “having
backup plans to manage changing
circumstances as a clinical trial progresses.”
Source: CRO Quality Benchmarking Report (released by Industry Standard Research,
a Cary, North Carolina CRO research firm in June 2011) is ISR’s annual survey of
pharmaceutical company executives and professionals from around the world.

34. Sustainability and the Feasibility of Studies
A Caution
“Today, wherever you stand in the world, the larger
part of the data from clinical trials comes from
somewhere else, so you have to have confidence in
the framework in which those trials were done.
… [T]here is no evidence that clinical trials conducted
in developing economies are any worse than those
done in the West. However, lack of evidence is not the
same as positive proof.”
Fergus Sweeney, head of compliance and inspections at the London-based EMA, Europe's equivalent of the
FDA as quoted in “Special report: Big Pharma’s global guinea pigs” (Reuters, May 6, 2011) --
http://www.reuters.com/article/2011/05/06/us-pharmaceuticals-trials-idUSTRE7450SV20110506

35. Governance
Accountability, liability of individuals
e.g.: “GSK Acquittal Casts Doubt On Government Cases That Target
Individuals” vs “FDA Increasingly Holding Executives Personally
Responsible For Violations” Media headlines on verdicts, May, 2011
Access & Transparency re: Trade Secrets/IP
“Drugmakers often succeed in convincing judges to issue protective orders
so that certain info - sometimes labeled as trade secrets - remains sealed.
And attorneys for plaintiffs generally agree in order to advance the cases.”
“A Senate Bill To Unseal Secret Pharma Documents,” Ed Silverman, May 19th, 2011, Pharmalot.com
… “’While it may hurt their business, the fact that the same information may
be hurting patients using their drug or devices should take priority over
their trade secrets.’ ”
David Egilman, an expert witness in litigation filed against drugmakers and a clinical associate professor in
the department of family medicine at Brown University.

36. Governance (continued)
Access & Transparency re: Rumors
“[Matrixx] argues [before the US Supreme Court] that rumors should not
have to be disclosed, but the government’s legal team countered that if the
rumors will influence stock prices, investors should be informed.”
FDLI SmartBrief (1/12/11) summarizing a New York Times (1/10/11) article
Access & Transparency and Physician Decision-making
“[R]esearchers say that despite the existence of hundreds of thousands of
clinical trials [,] doctors are unable to choose the best treatments for their
patients because results are reported selectively. This distorts the picture of
how well a drug works by leaving many negative trial results …
unpublished…. [They] are now calling on other drug regulatory agencies to
follow [EMA’s] suit … [making access to] documents … quicker and easier
for scientific scrutiny.”
From summary of a British Medical Journal article (Peter Gøtzsche and Anders Jørgensen, Denmark)
http://www.inpharm.com/news/156235/drug-regulators-protect-profits-over-patients-new-study-finds

37. Conclusion
The “paradigm-breaking” R&D world
of personalized medicine, translational science, etc.
combined with
Economic development priorities:
of developing as well as developed countries
Coincide for CSR to be a foundation for the
transformation of the clinical research
enterprise.

38. Between the Research Enterprise & Society
Economic
Public Health Development
FAIR
SUSTAINABLE
FEASIBLE VIABLE
Innovation

39. Thank you
Linda Strause, Ph.D Matthew Whalen, Ph.D
IMPACT LLC
Vical Incorporated Gambrills, MD
San Diego, CA contact@impactllc.info
lstrause@vical.com

40. Q&A

41. References
Foundations of Applied Research Ethics
 Nuremburg Code
 Declaration of Helsinki
 ICH (International Conference on Harmonisation)
 CIOMS (Council of International Organizations of Medical Sciences)
 EU Directive
 Belmont Principles
 Autonomy - Respect for persons
 Beneficence - do no harm
 Justice – equally for all

42. References
 Robinson, R. (2011). “CSR gets a Makeover.”
PharmaVOICE. June 2011.
 Schumpeter (2010). “Companies aren’t charities: In
poor countries the problem is not that businesses are
unethical but that there are too few of them.” The
Economist. October 21.
http://www.economist.com/node/17305554?story_id=17305554
 Schumpeter (2010). “Corporate constitutions: The
world knows less about what makes for good corporate
governance than it likes to think.” The Economist.
October 28.
http://www.economist.com/node/17359354?story_id=17359354

43. References (continued)
Karnani A. (2010). “The Case Against Corporate Social
Responsibility.” Wall Street Journal. August 23.
Whalen M, Goebel P. (2010). “From Silos to Bridges in
Clinical Research.” The Monitor. 24(3): 36-40.
Bertels S, Papania L, Papania D. (2010). “Embedding
Sustainability in Organizational Culture: A Systematic
Review of the Body of Knowledge.” Network for Business
Sustainability.
http://www.nbs.net/wp-content/uploads/Systematic-Review-Sustainability-an

44. References (continued)
 “Abbott Laboratories 2010 Global Citizenship Report”
http://www.abbott.com/static/cms_workspace/content/document/
 “Pfizer 2009 Corporate Responsibility Report”
http://www.pfizer.com/responsibility/corporate_responsibility_report.jsp
 Edwards, B., Olsen, A., Whalen, M., Gold, M. (2007)
“Guiding Principles of Safety as a basis for Developing a
Pharmaceutical Safety Culture.” Current Drug Safety. 2:
135-139.

45. References (continued)
 Santoro MA and Gorrie TM, eds. (2005) Ethics and the
Pharmaceutical Industry. Cambridge: Cambridge
University Press, including:
Koski G. “Renegotiating the Grand Bargain: Balancing
Price, Profits, People, and Principles”
 Murray, Alasdair, Corporate Social Responsibility in the
EU, Centre for European Reform (CER), 2003
 Emanuel EJ, Wendler D., Grady C., “What Makes
Clinical Research Ethical ?” Journal of the American
Medical Association (2000)