JiscMail Logo
Email discussion lists for the UK Education and Research communities

Help for EVIDENCE-BASED-HEALTH Archives


EVIDENCE-BASED-HEALTH Archives

EVIDENCE-BASED-HEALTH Archives


EVIDENCE-BASED-HEALTH@JISCMAIL.AC.UK


View:

Message:

[

First

|

Previous

|

Next

|

Last

]

By Topic:

[

First

|

Previous

|

Next

|

Last

]

By Author:

[

First

|

Previous

|

Next

|

Last

]

Font:

Proportional Font

LISTSERV Archives

LISTSERV Archives

EVIDENCE-BASED-HEALTH Home

EVIDENCE-BASED-HEALTH Home

EVIDENCE-BASED-HEALTH  August 2001

EVIDENCE-BASED-HEALTH August 2001

Options

Subscribe or Unsubscribe

Subscribe or Unsubscribe

Log In

Log In

Get Password

Get Password

Subject:

Re: Randomized versus non-randomized studies...equipoise etc...

From:

"Djulbegovic, Benjamin" <[log in to unmask]>

Reply-To:

Djulbegovic, Benjamin

Date:

Fri, 17 Aug 2001 22:49:56 -0400

Content-Type:

text/plain

Parts/Attachments:

Parts/Attachments

text/plain (153 lines)

 For some reason, the most interesting discussion always happens when I am
on (extremely busy) clinical service. Neverthless, let me try to highlight
some of the issues that I think have been forgotten over the years (some of
this, has been summarized in my recent article entitled "Acknowledgment of
Uncertainty: A Fundamental Means to Ensure Scientific and Ethical Validity
in Clinical Research" Current Oncology Reports 2001, 3 (5):389-95; will be
happy to forward a copy to those who are interested). (I appologize if what
follows sounds too didactic).

1. Why do we do (clinical) research?

Clinical research is done to resolve existing uncertainty (say, about
relative effects of two competing treatment alternatives). Thus, a clinical
trial is only justified if the patient (and clinician) are uncertain about
which treatment to choose from the available options. If we are not
uncertain, scientifically, nothing new would be learned, and ethically, we
would administer an inferior treatment (in at least half of our patients).

2. What are tools that are available to resolve the existing uncertainty?

It may come to surprise, but the best technique that has ever been developed
to resolve uncertainty about effects of health care interventions is- the
flip of coin. It should be remebered that randomization is just a technique
for resolution of the uncertainty-nothing more, nothing less. This is the
main difference between RCTs and Non-RCTs; in the former, it is chance that
decides for us, in the latter it was us that made decision about
treatment(s).

3. Our state of ignorance can range from not knowing, to uncertainty to
equipoise (which is equal to maximum uncertainty). The fact that we do not
know something does not justify experimental testing. Only if we are
uncertain ("indifferent") about the relative value of the treatments, it is
time for a trial. Equipoise is in our minds.  When there is "clash" (either
on collective or individual level) in interpretation of existing evidence,
tension is created that requires its resolution by undertaking a clinical
trial. [I should also mention that we have a model (unpublished at this
time), which shows that randomization is the best recourse for the
resolution of uncertainty under vast majority of circumstances].

4. Remember, the question of treatment is the question of comparison. The
key issue always relates to a choice of the control group. Practical
importance of acknowledgement of equipoise (or uncertainty) is that it is
only known mechanism that we have to ensure the choice of an adequate
control group. Studies can meet all other quality criteria regarding conduct
and design and still be biased if the control group is inferior or
inadequate. Randomization deals with selection bias, acknowledgment of
uncertainty deals with a choice of the control group.

I think I will stop now. Sorry for this long message. Looking forward to an
interesting debate.

ben djulbegovic
--

-----Original Message-----
From: Simon, Steve, PhD
To: [log in to unmask]
Sent: 8/17/01 9:00 PM
Subject: Re: Randomized versus non-randomized studies

David Doggett writes:

>This raises a point that has always puzzled me.  RCTs are
>only considered ethical if there is equipoise.  But what can the
>evidence be for equipoise? EBM only recognizes RCTs as valid
>evidence.  As far as I know, EBM is silent on what the evidence
>must be for equipoise.  Any thoughts anyone?

I addressed this topic (indirectly) in an email to the
Evidence-Based-Health
group and Jeanne Lenzer. I am working on this issue on a web page:

http://www.childrens-mercy.org/stats/plan/placebo.asp

that discusses the ethics of placebo controlled trials. As in the other
email, I want to encourage any of the readers of this group to provide
me
feedback. The page is still an early draft.

In the other email, I talked about lung reduction surgery for patients
with
severe emphysema. Many doctors embraced a 1996 study that compared 150
consecutive surgeries to a historical control group. They apparently
felt
that this non-randomized study was sufficient to upset equipoise in
favor of
the surgery, although a randomized trial has shown that the opposite was
true, at least for some patients.

Weijer, Shapiro, and Glass (2000) have argued that information "on
personal
experience, on anecdote, on tacit understanding, or rules of thumb" is
sufficient to upset equipoise but that a "hunch" is not sufficient.

That same article highlights the debate between the uncertainty
principle
(which I would call individual equipoise) and community equipoise. An
interesting argument would be that equipoise exists until a randomized
study
has been done. I have not heard anyone make that argument directly, but
is
appears to be implied by some arguments in favor of community equipoise.

Others have argued (see some of the arguments in William Silverman's
book)
that you need to randomize from the very first patient, before there is
a
chance for non-randomized data to upset equipoise. This strikes me as a
bit
naive. Some therapies require a bit of preliminary data before they can
even
be considered equivalent to placebo, because they have serious side
effects.
Furthermore, some therapies like surgery require some training and
experience before they can be incorporated into the context of a
clinical
trial. Besides, if equipoise is such a fragile thing that a few
preliminary
non-randomized patients can upset it, then why wouldn't promising
results in
an animal model also upset equipoise?

The issue is further clouded when a regulatory agency, such as the
United
States Food and Drug Administration, requires a strong level of evidence
(typically two randomized trials) before a new drug is approved.
Wouldn't
equipoise be violated in the replication study (the second study)?

And Stephen Senn has argued in an eLetter to the BMJ that equipoise is
not
required for an ethical trial.

Placebo confusion Stephen Senn,  BMJ eletters. 15 August 2000
www.bmj.com/cgi/eletters/321/7258/442

Where's the Evidence? : Debates in Modern Medicine by William A.
Silverman
(1999) Oxford Univ Press; ISBN: 0192630881.

For and against: Clinical equipoise and not the uncertainty principle is
the
moral underpinning of the randomised controlled trial * FOR * AGAINST
Charles Weijer, Stanley H Shapiro, Kathleen Cranley Glass, and Murray W
Enkin. BMJ 2000; 321: 756-758.

You can get the full text of this article from the bmj.com web site.

Steve Simon, [log in to unmask], Standard Disclaimer.
STATS: STeve's Attempt to Teach Statistics. http://www.cmh.edu/stats
Watch for a change in servers. On or around June 2001, this page will
move to http://www.childrens-mercy.org/stats

Top of Message | Previous Page | Permalink

JiscMail Tools


RSS Feeds and Sharing


Advanced Options


Archives

November 2019
October 2019
September 2019
August 2019
July 2019
June 2019
May 2019
April 2019
March 2019
February 2019
January 2019
December 2018
November 2018
October 2018
September 2018
August 2018
July 2018
June 2018
May 2018
April 2018
March 2018
February 2018
January 2018
December 2017
November 2017
October 2017
September 2017
August 2017
July 2017
June 2017
May 2017
April 2017
March 2017
February 2017
January 2017
December 2016
November 2016
October 2016
September 2016
August 2016
July 2016
June 2016
May 2016
April 2016
March 2016
February 2016
January 2016
December 2015
November 2015
October 2015
September 2015
August 2015
July 2015
June 2015
May 2015
April 2015
March 2015
February 2015
January 2015
December 2014
November 2014
October 2014
September 2014
August 2014
July 2014
June 2014
May 2014
April 2014
March 2014
February 2014
January 2014
December 2013
November 2013
October 2013
September 2013
August 2013
July 2013
June 2013
May 2013
April 2013
March 2013
February 2013
January 2013
December 2012
November 2012
October 2012
September 2012
August 2012
July 2012
June 2012
May 2012
April 2012
March 2012
February 2012
January 2012
December 2011
November 2011
October 2011
September 2011
August 2011
July 2011
June 2011
May 2011
April 2011
March 2011
February 2011
January 2011
December 2010
November 2010
October 2010
September 2010
August 2010
July 2010
June 2010
May 2010
April 2010
March 2010
February 2010
January 2010
December 2009
November 2009
October 2009
September 2009
August 2009
July 2009
June 2009
May 2009
April 2009
March 2009
February 2009
January 2009
December 2008
November 2008
October 2008
September 2008
August 2008
July 2008
June 2008
May 2008
April 2008
March 2008
February 2008
January 2008
December 2007
November 2007
October 2007
September 2007
August 2007
July 2007
June 2007
May 2007
April 2007
March 2007
February 2007
January 2007
December 2006
November 2006
October 2006
September 2006
August 2006
July 2006
June 2006
May 2006
April 2006
March 2006
February 2006
January 2006
December 2005
November 2005
October 2005
September 2005
August 2005
July 2005
June 2005
May 2005
April 2005
March 2005
February 2005
January 2005
December 2004
November 2004
October 2004
September 2004
August 2004
July 2004
June 2004
May 2004
April 2004
March 2004
February 2004
January 2004
December 2003
November 2003
October 2003
September 2003
August 2003
July 2003
June 2003
May 2003
April 2003
March 2003
February 2003
January 2003
December 2002
November 2002
October 2002
September 2002
August 2002
July 2002
June 2002
May 2002
April 2002
March 2002
February 2002
January 2002
December 2001
November 2001
October 2001
September 2001
August 2001
July 2001
June 2001
May 2001
April 2001
March 2001
February 2001
January 2001
December 2000
November 2000
October 2000
September 2000
August 2000
July 2000
June 2000
May 2000
April 2000
March 2000
February 2000
January 2000
December 1999
November 1999
October 1999
September 1999
August 1999
July 1999
June 1999
May 1999
April 1999
March 1999
February 1999
January 1999
December 1998
November 1998
October 1998
September 1998


JiscMail is a Jisc service.

View our service policies at https://www.jiscmail.ac.uk/policyandsecurity/ and Jisc's privacy policy at https://www.jisc.ac.uk/website/privacy-notice

Secured by F-Secure Anti-Virus CataList Email List Search Powered by the LISTSERV Email List Manager