Midwife crisis: A cultural and financial mandate for talking

to research participants

Misha Angrist, PhD

Future of Genomic Medicine VI

La Jolla, California

7 March 2013

Disclosure

• I serve on the Duke University Health System

Institutional Review Board but I do not speak

for it nor do I speak for Duke University.

• They mostly think I’m crazy

“Ah but it’s hard to live by the rules. I never could…and

still never do”– Chrissie Hynde

“Talk of the Town”

Photo: Carlos Alvarez/Getty Images

The Institutional Review Board

Juror #10: I want to ask you something: do you believe his story?Juror #8: I don’t know whether I believe it or not – maybe I don’t.Juror #7: So how come you vote not guilty?Juror #8: Well, there were eleven votes for guilty. It’s not easy to raise my hand and send a boy off to die without talking about it first.

Case #1, 2012:

A massive biobank and the impossibility of sending

participants a Christmas card

• YOU will get NO compensation.

• But WE will try to make money from your samples

• We can come back to you to get MORE

• You aren’t allowed to see your own data

• If you get injured in OUR STUDY, we will treat you…but the bill goes TO YOU.

• At least you’re not giving up any of your rights!

My proposal

"If you wish to receive an annual

notification of which research groups are

studying your samples and a brief

description of what they are studying,

please provide an email address at the end

of this consent form.”

Response #1

• Yearly newsletter and list of publications?

• No personal contact because of this scenario: “Patient gets very excited and wants her results (‘just tell me if I am one of the ones who needs chemo’). Results cannot be released. Patient ends up very unhappy.”

• Bottom line: we can’t have patients badgering researchers

My second proposal

“What if you left off the PI's name and

institution and just briefly described the

specific research projects in which the

patient's sample was being used? That way

the repository remains the gatekeeper.”

PI Response #2

• “Let me think about it.”

• “The repository may not have a clear understanding of the research that is being done on a patient’s tissue”

• “We are a disinterested third party”

• “I am not sure how to make a patient-specific communication work.”

My third communiqué

• “I’m not asking for a detailed understanding of what

specific investigators are doing”

• “…provide a couple of sentences from the external

investigator's IRB-approved protocol in plain English”

• “In my opinion it is exactly that piece--the

personal acknowledgement--that would add

value to the participants and ultimately redound

to you and the repository.”

PI Response #3

Case #2, 2012:

Warfarin genotyping and the meaning of the word “clinical”

“Dear Dr. X…

Your consent form says: ‘The tests done for this

study are for research purposes only. Therefore, you

will receive no results from these genetic studies…’

But both the genotyping and the INR measurements

will be done in CLIA-certified labs. If that's true, then

I am wondering why participants should not have

access to their CYP2C9/VKORC1 genotypes and their

INR values?”

“Dear Misha…

The INR results are considered standard of care.

Everyone has access to the INR results. The genotype

testing is being performed by research personnel.

While it is being performed in a CLIA laboratory it is

for research only…The additional costs associated

with providing genetic counseling for this purpose

[were] not in the NIH budget for this study.”

Even the bioethicists are giving up on this idea

Case #3, 2013:

“Dear Pancreatic Cancer Patient: We assume that you’re dead. But

this annoying dude on the IRB insists we try to contact you.”

http://pancreaticcancersymptoms.biz/category/what-is-pancreas/pancreatic-cancer-survival-rate

“A Phase III Trial of DRUG X or Placebo in Combination with DRUG Y as First-line Therapy for

Metastatic Adenocarcinoma of the Pancreas”

• August 2012: sponsor ends study on

account of futility

• PI: “We have communicated the

findings to the two subjects on study”

• Me: “Have you told the other five?”

• IRB: “Well, we usually don’t.”

Pyrrhic Victory is Mine!

“The study team must inform the

IRB on how it plans on informing

the five people who completed the

study about the reason why the

study was closed.”

What do these cases reveal?

• A reluctance to share even basic information with participants

• Fealty to the rules rather than people• Unilateral and maybe arbitrary decisions

about what constitutes research• Genetic exceptionalism• Institutional detachment• Lack of resources

How might we address the lack of a culture of transparency and

dedicated resources for communication with

participants?

Scientific publishing: the good old days

“…more specific services may eventually supplant conventional journal publication…Any process of supplanting can therefore be evolutionary, with no direct and immediate threat to the status quo; (the status quo being defined as the mess we are in). I especially wish to emphasize that I by no means advocate the deliberate proliferation of uncontrolled and informal communication.

American Psychologist, Vol 21(11), Nov 1966, 1005-1010

“Unimpeded access to these archives and open distribution of their contents will enable researchers to take on the challenge of integrating and interconnecting the fantastically rich, but extremely fragmented and chaotic, scientific literature.”

4 May 2001

“Midwives have found it possible to earn a living by delivering babies for a fee and turning them over immediately to their parents. We see no reason to doubt that scientific publishing can readily operate on a midwife model…”

Midwifery

Reasonable doubt?

“People were saying that PLoSwas plotting the overthrow of the scientific publishing system”

Pitchforks and torches

2011-2012: Access agonistes

The new normal?

But does it work?

Paying the cost to be the boss

Back in black

$

Closing thoughts• We can argue about CLIA and HIPAA, but those types of

rules have long since ossified into fig leaves and excuses • If it hadn’t already, the clear research-clinical divide ended

when Nic Volker had his DNA sequenced in 2009 • The same doubts, lack of incentives and lack of

infrastructure that kept open-access publishing down are inhibiting us from talking to the people we study

• The same types of incentives and infrastructure that fostered open-access publishing can be applied to participant communication

• If we are to monetize human tissue and information, should not some of that filthy lucre be funneled back into ways to inform and engage the people from whom the material and data came?

Acknowledgements

Duke

Sara Katsanis

Nico Katsanis

Erica Davis

Mike Cotten

Heidi Cope

Azita Sadeghpour

Leigh Ann Simmons

John Wiener

David Goldstein

Bob Cook-Deegan

Elsewhere

George Church (Harvard; PGP)

Michelle Meyer (Harvard)

Dan Vorhaus (PGP)

Jason Bobe (Harvard; PGP)

Leila Jamal (Johns Hopkins)

Sharon Terry (Genetic Alliance)

Jen Wagner (Penn)

Gholson Lyon (CSHL)

“I am a man of substance, of flesh and bone, fiber and liquids—and I might even be said to possess a mind. I am invisible, understand, simply because people refuse to see me.”

- Ralph Ellison (1914-1994),Invisible Man