Success in Clinical Investigation: Benefits and Pitfalls of Collaboration

1
Success in Clinical Investigation Benefits and
Pitfalls of Collaboration 
GI Education Series Key Elements of Academic Life

• Ray E. Clouse, M.D.
• Professor of Medicine and Psychiatry

2
Investigative Career Evolution
Mentoring by Dr. David Alpers
1978
Psychiatric disorder in GI illness
Collaboration with Dr. Patrick Lustman
Mind-body relationships
1981
Defining esophageal motor disorders
Collaboration with Dr. Annamaria Staiano
1982
Spastic disorders as a functional marker
Description of antidepressants for FGIDs
1985
Limited industry funding
Origin of high-resolution manometry
Co-investigator, NIH funding
1990
Treatment trials for diabetic depression
Industry partnerships
2002
Depression and insulin resistance
2004
Creation of high-definition manometry
Patent applications
3
Investigative Career Evolution
Mentoring by Dr. David Alpers
1978
Psychiatric disorder in GI illness
Collaboration with Dr. Patrick Lustman
Mind-body relationships
1981
Defining esophageal motor disorders
Collaboration with Dr. Annamaria Staiano
1982
Spastic disorders as a functional marker
Description of antidepressants for FGIDs
1985
Limited industry funding
Origin of high-resolution manometry
Co-investigator, NIH funding
1990
Treatment trials for diabetic depression
Industry partnerships
2002
Depression and insulin resistance
2004
Creation of high-definition manometry
Patent applications
4
Investigative Career Evolution
Mentoring by Dr. David Alpers
1978
Psychiatric disorder in GI illness
Collaboration with Dr. Patrick Lustman
Mind-body relationships
1981
Defining esophageal motor disorders
Collaboration with Dr. Annamaria Staiano
1982
Spastic disorders as a functional marker
Description of antidepressants for FGIDs
1985
Limited industry funding
Origin of high-resolution manometry
Co-investigator, NIH funding
1990
Treatment trials for diabetic depression
Industry partnerships
2002
Depression and insulin resistance
2004
Creation of high-definition manometry
Patent applications
5
Investigative Career Evolution
Mentoring by Dr. David Alpers
1978
Psychiatric disorder in GI illness
Collaboration with Dr. Patrick Lustman
Mind-body relationships
1981
Defining esophageal motor disorders
Collaboration with Dr. Annamaria Staiano
1982
Spastic disorders as a functional marker
Description of antidepressants for FGIDs
1985
Limited industry funding
Origin of high-resolution manometry
Co-investigator, NIH funding
1990
Treatment trials for diabetic depression
Industry partnerships
2002
Depression and insulin resistance
2004
Creation of high-definition manometry
Patent applications
6
Great Collaborations
Rodgers Hammerstein
Capitalize on disparate skills of the
collaborators
Masters Johnson
Collective momentum to accomplish a difficult
project
Antony Cleopatra
Joining forces to conquer otherwise
insurmountable hurdles
Sherlock Holmes Watson
Complementary roles or personalities
The Lenon Sisters
The power of similarity
James Kilpatrick Shana Alexander
Energy of dialogue and dissimilar views
7
The Successful Clinical Investigator Must Write

• Your ideas are not known or valuable unless they
  are exposed for consideration and discussion
• Publication track record is essential to remain
  competitive for sustained funding
• Reaching thought leader status requires a broad
  sphere of influence
• Successful evolution of your own thoughts
  requires critical feedback

8
Collaboration and Productivity
9
Collaboration and Productivity
10
Academic Expectations Can Deter Collaboration

• Independent ideas
• Research identity
• Independent funding
• His or her own lab
• Principal investigator

11
Science Increasingly Depends on Collaboration

Articles published in Science
Mussurakis, 1993, Khan et al. 1999
12
Rise in Collaborations Has Resulted from Many
Factors

• No single person has skills, knowledge, resources
  to address all research problems (judicious
  choice of collaborators can save considerable
  time and money)
• Funding/structure of science favors programs with
  authorities in each key area
• Breakthroughs are more likely from collaborations
  across disciplines
• Academia/private sector collaboration favored by
  legislation, industry, and academia
• Collaborations are easier than they once were

13
Assessing a Collaborative Opportunity

• Do I need this collaboration in order to move my
  own work forward? Is there a missing piece that
  I must have?
• Even if not strictly necessary, will a
  collaboration help me make a significant
  scientific contribution?
• Do I have the expertise or resources sought by
  the other collaborator?
• Can this collaboration be conducted efficiently?
• Is there funding for the work envisioned?
• Can I afford the time?

14

• Is this person someone with whom I want to
  collaborate?
• Are our professional and scientific interests
  compatible?
• Will this person be accessible to me and
  consistently interested in the project?
• What exactly is being asked of me?
• Can I exclude potential conflicts, either
  professional or institutional?
• Before making a decision, consider all factors.
  A good collaboration can take your research in an
  unexpected course a bad one will siphon off
  energy and demoralize you.

McGovern V, et al. Setting Up Collaborations.
In BWF, HHMI. Making the Right Moves A
Practical Guide to Scientific Management for
Postdocs and New Faculty, 2004
15
Personal Qualities of a Good Collaborator

• Honesty
• Openness
• Fairness
• Industry
• Respect
• Reliability

Disclosure, constructive criticism Availability,
problem resolution Giving credit where credit is
due Effort, carrying ones weight Appreciation of
each contribution Delivering on time
McGovern V, et al. Setting Up Collaborations.
In BWF, HHMI. Making the Right Moves A
Practical Guide to Scientific Management for
Postdocs and New Faculty, 2004
16
Responsible Collaborations are Defined by
Openness and Communication

• Collaborators should be open about the research
• Communal enterprise
• Collegiality
• Collaborators should be open and clear about the
  terms of the collaboration
• Expectations communicated
• Nature of sharing

17
Collaborations Are a Frequent Source of Problems

• Failed start-up because of reluctance to share or
  work together
• Misunderstandings of what is to be provided by
  each participant
• Unhappiness with a slow collaborator
• Disagreement about what and when to publish
• Conflicts regarding authorship and credit

Cohen J. Science 1995 Kahn JO et al. JAMA
2000 Wilcox LJ. JAMA 1998
18
Game Theory and the Prisoners Dilemma

• In game theory, the prisoner's dilemma is a type
  of non-zero-sum game in which two players can
  "cooperate" with or "defect" (i.e. betray) the
  other player. In this game, as in all game
  theory, the only concern of each individual
  player ("prisoner") is maximizing his/her own
  payoff, without any concern for the other
  player's payoff.

Situations where participants can all gain or
suffer together, such as a country with an excess
of bananas trading with another country for their
excess of apples, where both benefit from the
transaction, are referred to as non-zero-sum.
19
The Prisoners Dilemma
Two suspects, A and B, are arrested by the
police. The police have insufficient evidence for
a conviction, and, having separated both
prisoners, visit each of them to offer the same
deal if one testifies for the prosecution
against the other and the other remains silent,
the betrayer goes free and the silent accomplice
receives the full 10-year sentence. If both stay
silent, both prisoners are sentenced to only six
months in jail for a minor charge. If each
betrays the other, each receives a two-year
sentence. Each prisoner must make the choice of
whether to betray the other or to remain silent.
However, neither prisoner knows for sure what
choice the other prisoner will make. So this
dilemma poses the question How should the
prisoners act?
20
Game Theory and the Prisoners Dilemma
The dilemma can be summarized thus
The dilemma arises when one assumes that both
prisoners only care about minimizing their own
jail terms.
21
The Prisoners Dilemma Iterated
Greedy strategies do poorly Altruistic
strategies do better
Robert Axelrod. The Evolution of Cooperation,
1984
22
The Prisoners Dilemma Iterated Axelrod
Conditions for a Successful Strategy

• Nice
• Mostly important, the strategy must be "nice",
  that is, it will not defect before its opponent
  does.
• Retaliating
• However, the successful strategy must not be a
  blind optimist. It must always retaliate. An
  example of a non-retaliating strategy is always
  cooperate. This is a very bad choice, as "nasty"
  strategies will ruthlessly exploit such softies.
• Forgiving
• Though they will retaliate, they will once again
  fall back to cooperating if the opponent does not
  continue to play defects. This stops long runs of
  revenge and counter-revenge, maximizing points.
• Non-envious
• The last quality is not striving to score more
  than the opponent.

23
Strategies with Varying Investment in
CooperationRoberts G, Sherratt TN. Nature 1998

• Non-altruism (NA) never investing
• Give-as-good-as-you-get (GGG) matching what the
  partner last gave
• Short-changer (SC) giving a little less than the
  partner
• Raise-the-stakes (RTS) offering a small amount
  on first meeting and then, if matched, raising
  the investment

24

• In human models, anecdotal and scientific
  evidence that cooperation is greater in people
  who know each other well
• Strategies to move from uncooperative strangers
  to cooperative friends are unknown
• Tested RTS and GGG strategies in a varying
  investment game

Proceedings of the Royal Society B Biological
Sciences 2003
25
Game Paradigms
A
B
x
2x
I
A
B
2y
y
I
Free response, actual partner
Roberts G, Renwick JS, Proc Royal Soc B, 2003
26
Playing against a matched response stooge
Playing against a free response partner
27
The Prisoners Dilemma Iterated Axelrod
Conditions for a Successful Strategy

• Nice
• Mostly important, the strategy must be "nice",
  that is, it will not defect before its opponent
  does.
• Retaliating
• However, the successful strategy must not be a
  blind optimist. It must always retaliate. An
  example of a non-retaliating strategy is always
  cooperate. This is a very bad choice, as "nasty"
  strategies will ruthlessly exploit such softies.
• Forgiving
• Though they will retaliate, they will once again
  fall back to cooperating if the opponent does not
  continue to play defects. This stops long runs of
  revenge and counter-revenge, maximizing points.
• Non-envious
• The last quality is not striving to score more
  than the opponent.

28
The Mantle of Leadership Belongs to the Team

• In a complex and technologically sophisticated
  society, the most urgent projects require
  coordinated contributions of many talented people
• We cling to the romantic idea that great things
  usually are accomplished by larger-than-life
  individuals working alone
• Despite evidence to the contrary, we still tend
  to think of achievement in terms of the Great Man
  or Great Woman, instead of the Great Group

Even the Lone Ranger belonged to a team
Bennis W, Biederman PW. Organizing Genius The
Secrets of Creative Collaboration. Cambridge,
Mass. Perseus, 1997
29
The Mantle of Leadership Belongs to the Team

• New leadership paradigms
• Not great leaders alone, but great leaders who
  exist in a fertile relationship with a great
  group
• Creative alliances wherein leader and team
  achieve something together that neither could
  achieve alone
• The leader finds greatness in the group and helps
  members find it in themselves

Bennis W, Biederman PW. Organizing Genius The
Secrets of Creative Collaboration. Cambridge,
Mass. Perseus, 1997
30
Summary

• Science increasingly depends on collaboration
• Responsible collaborations are defined by
  openness and communication
• Successful behaviors in a collaborative
  relationship can be predicted from game theory
  strategies for cooperation
• Nice, retaliating, forgiving, non-envious
• Altruistic strategies are superior to greedy
  strategies
• Collaboration also is necessary for successful
  leadership by the investigator

31
(No Transcript)