FEATURE
Features
Contract Research Organizations:
Outsourced Trials, Outsized Problems
A ranking of sorts is sent out every week to
the chosen ones, but those who find them-
selves in the top spots don’t feel lucky at all:
They are clinical trial investigators whose
sites have just been singled out by contract
research organizations (CROs) for having
the highest number of outstanding queries.
To be fair, it would be hard not to ignore
most of these queries. Out of 100, only one
may be related to a serious patient-safety
event that merits attention from the investiga-
tor, leaving 99 irrelevant distractions, said
Andrew Wei, MBBS, PhD, an acute myeloid
leukemia researcher at Monash University
and Alfred Hospital in Melbourne, Australia.
“This makes some sites look bad be-
cause they had 120 queries,” he said. “The
CROs don’t take into account that these
sites also had the most patients.” Still, it’s a
risk that researchers don’t want to take, and
they are obliged to respond to all queries.
This perceived stranglehold on clinical
trial conduct has bred resentment between
investigators and CROs, with some
researchers doubting the usefulness and
intentions of these organizations.
“CROs [release these lists] purely to
humiliate and embarrass the principal inves-
tigators as a way of bullying sites into address-
ing the queries quickly,” Dr. Wei told ASH
Clinical News. “Our coordinators are being
harassed [and] asked to answer really stupid
queries clearly generated by people who don’t
understand medicine. Some queries are ask-
ing us to educate them on what to do.”
Humiliation and harassment of trial
investigators is not what pharmaceutical
companies intend when they decide to
outsource data management and biostatis-
tical analysis to a CRO. And it’s certainly
not what CROs sign up for when they
agree to take over a sponsor’s clinical trial.
“CROs pursue innovation in clini-
cal trials because a competitive industry
demands it, and because it’s what patients
awaiting new medicines deserve,” accord-
ing to the Association of Clinical Research
Organizations (ACRO), the trade orga-
nization representing CROs. “Research
sponsors choose to work with [CROs]
because they have confidence [they] will
work tirelessly to conduct safe, thorough
trials on schedule and within budget.” 1
Unfortunately, to meet those demands
while adhering to regulatory and protocol
guidelines, CROs are compelled and often in-
centivized to “bully” investigators. CROs are
an easy target for researchers’ frustrations, but
are CROs victims of the same bureaucracy
plaguing investigators and research sites?
ASHClinicalNews.org
Birth of an Aggravation
When the first CROs came onto the scene in
the 1980s, they aimed to help industry part-
ners bring new treatments to patients more
quickly and efficiently. This same decade, the
U.S. Food and Drug Administration (FDA)
completely reworked clinical trial design.
The agency stopped approving drugs
on a study-by-study basis; each investiga-
tional drug submitted for review had its en-
tire body of evidence evaluated. New Drug
Application submissions required increas-
ingly detailed information. The agency also
deemed surrogate endpoints acceptable for
approval in data analyses, giving lovastatin
the green light in 1987 based on the sur-
rogate of reduced cholesterol. 2
Pharmaceutical companies felt com-
pelled to hire professional help to cope
with the change. In 1982, Quintiles arrived
on the biostatistics consulting scene, and
the National Cancer Institute contracted
with Theradex Oncology Experts to moni-
tor its clinical trials. 2
Today, Quintiles (now IQVIA, after
merging with IMS Health) is a full-service
CRO in a field teeming with competitors
who offer assistance with everything from
selection of investigators and sites to recruit-
ing trial participants.
For readers who have not yet been
initiated into the CRO club, the relationship
unfolds as follows: The CRO’s monitor meets
the study team (nurses, pharmacists, research
coordinators, and other physicians) for a site-
initiation visit; the representative reviews the
trial’s protocol and investigators’ responsibili-
ties and then tours the site. What comes next
is usually a revolving door of site monitors,
reminders about upcoming visits, updates
about prior visits, and requests to complete
documentation through the CRO’s website.
Queries are one way that CROs com-
municate with on-site study coordinators
and clinical investigators, with the intent
of getting researchers to respond to issues
of patient safety, drug efficacy, or the study
process. In reality, though, queries may be
picky or identify issues that are irrelevant
to patient safety or study conduct and may
grow in number as the pressure to address
them evolves into an entirely different
animal, as observed by Dr. Wei.
The View From the Other Side
Despite their reputation as bureaucratic
bullies, CROs certainly have their
own battles to fight. “It is in everyone’s
interest for clinical trials to be more
efficient,” said Matt Feldman, director of
communications for ACRO. “We work
with our members to address challenges
faced by CROs, as innovations in
technology, for example, change the way
that trials are conducted.”
The demands of the pharmaceutical
sponsors who contract with CROs also rep-
resent their own challenge. Some sponsors
are now moving from longstanding relation-
ships with a single CRO to three- to five-year
contracts with mult