Matt Whalen & Linda Strause GCT 2012

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 TrialsPhiladelphia, PA, USA

September 15-16, 2011

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 KoskiEthics and the Pharmaceutical Industry (2005)

Public Mistrust

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

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)

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

Between the Research Enterprise & Society

Public Health

Innovation

Economic Development

FEASIBLE VIABLE

FAIR

SUSTAINABLE

“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

Corporate Social ResponsibilityA brief Overview

CSR has evolved to focus on:

Business Ethics

Enterprise Sustainability

Corporate Governance

….on a global scale, given

the international nature

of business.

CSR in the 21st Century

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

To ‘translate’ CSR to Clinical Research

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 REGIONSSingle Market Act Twelve levers to boost growth and strengthen

confidence "Working together to create new growth” § 2.8 Social Entrepreneurshiphttp://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:52011DC0206:EN:NOT

Reinforcement:The EU’s Single Market Act & CSR

The 10 principles of the Compact with international business focus on:

Human Rights (i.e., abuses, collective bargaining, child labor, discrimination);

Environment (i.e., challenges, responsibilities, and ‘friendly’ technologies); and,

Transparency (anti-corruption in all its forms, including extortion and bribery).

unglobalimpact.org

Reinforcement:The U.N. Global Compact and CSR

Applied Research Ethics

“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” seriesWashington (DC) Post, 1998 – 1999

Scientific Advances … ramifications

1. Social and Scientific Value2. Scientific Validity3. Fair Subject Selection4. Favorable Risk-Benefit Ratio5. Independent Review6. Informed Consent7. Respect for Enrolled Subjects8. Community Perspective

Applied Research Ethics: 8 Principles for International Trials

NIH’s Center for Bioethics

“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.

Applied Research Ethics: Social Value & Community Perspective

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.

Applied Research Ethics: Scientific Validity & Fair Subject Selection

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

Applied Research Ethics: Risk/Benefit Ratio & Respect for Subjects

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”)

Applied Research Ethics: Independent Review & Informed Consent

“…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

Applied Research Ethics: Therapeutic misconception

“… [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.

Applied Research Ethics: Coercion

In a study of terminally ill cancer patients whoenrolled 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%


2011 The Hastings Center: Unrealistic Optimism in Early-Phase Oncology Trials, Jansen, et.al.

IS THIS COERCION?

In a study of terminally ill cancer patients whoenrolled 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%


2011 The Hastings Center: Unrealistic Optimism in Early-Phase Oncology Trials, Jansen, et.al.

This is NOT coercion since cancer is generating the pressure

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

Ethical PerspectiveTherapeutic misconception

Patients seek new drugs for hope of personal benefit

New drugs need testing in clinical trials

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

Applied Research Ethics: a Balancing Act

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

Applied Research Ethics: HOPE

Is HOPE a deterrent to clinical trial participation?

-- Personal Story

“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)

Applied Research Ethics: Situational Ethics

The ethical decisions that we make are more often NOT between Good and Bad

but between Good and Good.

Enterprise Sustainability(including Feasibility of Studies)

& Governance

Enterprise Sustainability“Paradigm-breaking business …”

“… transitions to sustainability may involve the need for paradigm-breaking business models or approaches.”

Perhaps like … New Regulatory Science Systems thinking/Holistic approach (e.g., MIT)

Alternative/Complimentary Medicine research “Virtual Physiologic Human” (e.g., Univ. of Nottingham +)

“Culture of Safety” Collaborations in research (e.g., PhRMA and academic Research Centers)

Translational Science (e.g., NCATS -- government and industry)

“Point-of-Care” Clinical Trials Adaptive Trial Design (especially Phases II, II/III)

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

Enterprise SustainabilityPublic Health-centric Prioritizing

including competing for scarce resources

Record of abiding by International Standards, including any history of ethical abuses and established track-record of robustness of review (regulatory/ethics) processes

Determining what exists as a Standard of Care Correlation of protocol with overall as well as disease state-specific research experience

Prioritized Populations based on country- specific health authorities and objectives

Adequacy of safety profiles including any comparators and rescue medications

Sustainability and the Feasibility of StudiesStandards, Experience, Priorities as CSR

Sustainability and the Feasibility of StudiesWhat Sponsors look for in CROs

and being socially responsible

1. therapeutic expertise 2. cost feasibility/viability 3. a global footprint4. clinical research associates quality; and,5. 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.

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

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.

Access & Transparency re: Rumors“[Matrixx] argues [before the US Supreme Court] that rumors should nothave to be disclosed, but the government’s legal team countered that if therumors 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 ofclinical trials [,] doctors are unable to choose the best treatments for theirpatients because results are reported selectively. This distorts the picture ofhow well a drug works by leaving many negative trial results …unpublished…. [They] are now calling on other drug regulatory agencies tofollow [EMA’s] suit … [making access to] documents … quicker and easierfor 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

Governance (continued)

The “paradigm-breaking” R&D worldof 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.

Conclusion

Between the Research Enterprise & Society

Public Health

Innovation

Economic Development

FEASIBLE VIABLE

FAIR

SUSTAINABLE

Thank youLinda Strause, Ph.D

Vical Incorporated

San Diego, [email protected]

Matthew Whalen, Ph.DIMPACT LLC

Gambrills, [email protected]

Q&A

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

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

References

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-and-Corporate-Culture.pdf

References (continued)

“Abbott Laboratories 2010 Global Citizenship Report”http://www.abbott.com/static/cms_workspace/content/

document/Citizenship/Reports/gc_report_2010.pdf

“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.


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)
