Group Title: BMC Health Services Research
Title: Factors influencing the participation of gastroenterologists and hepatologists in clinical research
CITATION PDF VIEWER THUMBNAILS PAGE IMAGE ZOOMABLE
Full Citation
STANDARD VIEW MARC VIEW
Permanent Link: http://ufdc.ufl.edu/UF00099958/00001
 Material Information
Title: Factors influencing the participation of gastroenterologists and hepatologists in clinical research
Physical Description: Book
Language: English
Creator: Dev, Anouk
Kauf, Teresa
Zekry, Amany
Patel, Keyur
Heller, Karen
Schulman, Kevin
McHutchison, John
Publisher: BMC Health Services Research
Publication Date: 2008
 Notes
Abstract: BACKGROUND:Although clinical research is integral to the advancement of medical knowledge, physicians face a variety of obstacles to their participation as investigators in clinical trials. We examined factors that influence the participation of gastroenterologists and hepatologists in clinical research.METHODS:We surveyed 1050 members of the American Association for the Study of Liver Diseases regarding their participation in clinical research. We compared the survey responses by specialty and level of clinical trial experience.RESULTS:A majority of the respondents (71.6%) reported involvement in research activities. Factors most influential in clinical trial participation included funding and compensation (88.3%) and intellectual pursuit (87.8%). Barriers to participation were similar between gastroenterologists (n = 160) and hepatologists (n = 189) and between highly experienced (n = 62) and less experienced (n = 159) clinical researchers. These barriers included uncompensated research costs and lack of specialized support. Industry marketing was a greater influence among respondents with less trial experience, compared to those with extensive experience (15.7% vs 1.6%; P < .01). Hepatologists and respondents with extensive clinical trial experience tended to be more interested in phase 1 and 2 studies, whereas gastroenterologists and less experienced investigators were more interested in phase 4 studies.CONCLUSION:This study suggests that the greatest barrier to participation in clinical research is lack of adequate resources. Respondents also favored industry-sponsored research with less complex trial protocols and studies of relatively short duration.
General Note: Start page 208
General Note: M3: 10.1186/1472-6963-8-208
 Record Information
Bibliographic ID: UF00099958
Volume ID: VID00001
Source Institution: University of Florida
Holding Location: University of Florida
Rights Management: Open Access: http://www.biomedcentral.com/info/about/openaccess/
Resource Identifier: issn - 1472-6963
http://www.biomedcentral.com/1472-6963/8/208

Downloads

This item has the following downloads:

PDF ( PDF )


Full Text


0
BMC Health Services Research B1oledCentral


Research article


Factors influencing the participation of gastroenterologists and
hepatologists in clinical research
Anouk T Devt1,2,4, Teresa L Kauft1,3,5, Amany Zekry1,2,6, Keyur Patel1l3,
Karen Heller', Kevin A Schulman1,3 and John G McHutchison*1,2

Address: 'Duke Clinical Research Institute, PO Box 17969, Durham, North Carolina, USA, 'Division of Gastroenterology, Department of
Medicine, Duke University School of Medicine, Durham, North Carolina, USA, 3Division of General Internal Medicine, Department of Medicine,
Duke University School of Medicine, Durham, North Carolina, USA, 4Monash University, Melbourne, Australia, 5University of Florida,
Gainesville, USA and 6University of New South Wales, Sydney, Australia
Email: Anouk T Dev anouk.dev@ med.monash.edu.au; Teresa L Kauf- tkauf@ufl.edu; Amany Zekry a.zekry@unsw.edu.au;
Keyur Patel keyur.patel@duke.edu; Karen Heller karen.heller@duke.edu; Kevin A Schulman kevin.schulman@duke.edu;
John G McHutchison* mchut001@mc.duke.edu
* Corresponding author tEqual contributors



Published: 8 October 2008 Received: 30 April 2008
BMC Health Services Research 2008, 8:208 doi: 10.1 186/1472-6963-8-208 Accepted: 8 October 2008
This article is available from: http://www.biomedcentral.com/1472-6963/8/208
2008 Dev et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.



Abstract
Background: Although clinical research is integral to the advancement of medical knowledge,
physicians face a variety of obstacles to their participation as investigators in clinical trials. We
examined factors that influence the participation of gastroenterologists and hepatologists in clinical
research.
Methods: We surveyed 1050 members of the American Association for the Study of Liver
Diseases regarding their participation in clinical research. We compared the survey responses by
specialty and level of clinical trial experience.
Results: A majority of the respondents (71.6%) reported involvement in research activities.
Factors most influential in clinical trial participation included funding and compensation (88.3%) and
intellectual pursuit (87.8%). Barriers to participation were similar between gastroenterologists (n
= 160) and hepatologists (n = 189) and between highly experienced (n = 62) and less experienced
(n = 159) clinical researchers. These barriers included uncompensated research costs and lack of
specialized support. Industry marketing was a greater influence among respondents with less trial
experience, compared to those with extensive experience (15.7% vs 1.6%; P < .01). Hepatologists
and respondents with extensive clinical trial experience tended to be more interested in phase I
and 2 studies, whereas gastroenterologists and less experienced investigators were more
interested in phase 4 studies.
Conclusion: This study suggests that the greatest barrier to participation in clinical research is lack
of adequate resources. Respondents also favored industry-sponsored research with less complex
trial protocols and studies of relatively short duration.







Page 1 of 11
(page number not for citation purposes)


EOpen Ac







http://www.biomedcentral.com/1472-6963/8/208


Background
Physicians who participate in clinical research contribute
to the expanding knowledge base of medicine and have
opportunities to offer their patients cutting-edge thera-
pies. In addition, participation in clinical research is likely
to benefit physicians by satisfying intellectual curiosity,
increasing research opportunities, and aiding career
advancement [1]. Previous studies have documented sub-
stantial barriers to participation, such as bureaucracy, lack
of time, laboriousness, and insufficient financial reim-
bursement. These barriers prevent otherwise interested
physicians from participating in research [2-4]. There is
enormous potential in the biomedical sciences for trans-
lating new knowledge and technological capability into
powerful tools for the prevention and treatment of dis-
ease. However, as recently stated by the Association of
American Medical Colleges (AAMC) Clinical Research
Summit, this potential is unlikely to be reached without
greater participation in clinical research and a robust
national program of research that "enjoys the participa-
tion and harnesses the full strength of all components of
the health sector" [5].

Financial incentives have been shown to be among the
most important factors motivating physician involvement
in research [2,3,6,7]. In the United States, funding for bio-
medical research principally comes from industry and pri-
vate sources. Currently, the National Institutes of Health
and other government sources provide only 28% of
research funding [8]. Clinical trials, and industry-spon-
sored trials in particular, which often carry greater reim-
bursement, are now viewed as essential sources of income
for the maintenance of research programs and staff [9].
Recent research also indicates that academic-industry rela-
tionships in medicine have substantial benefits for indus-
try sponsors and that the rate of industry support for
clinical research is likely to increase [10]. Researchers in
gastroenterology and hepatology will not be immune to
this trend and may be forced to choose between conduct-
ing investigator-initiated research and that which is deter-
mined by industry interests [11,12]. There also could be a
difference in clinical experience and participation rates
between proceduralists (gastroenterologists) and nonpro-
ceduralists (hepatologists) and between physicians in pri-
vate practice and those working predominantly in
hospitals, as observed in previous studies [7,11]. In this
study, we examined the factors that influence the partici-
pation of gastroenterologists and hepatologists in clinical
research and identified the most important criteria in
choosing to participate in competing trials.

Methods
We developed a questionnaire to document respondents'
demographic characteristics, factors that influence physi-
cian participation in research, factors important in enroll-


ing patients in clinical trials, and respondents' preferences
for types of research [see Additional file 1]. In addition,
themes relating to barriers to participation and methods
of financial reimbursement obtained from published lit-
erature were used to generate questions. An exploratory
survey including these themes was given to a group of
eight experienced physician-researchers in an open-ended
or free-response format. The responses from this survey
and ensuing discussion were used to generate fixed-alter-
native questions used in the final questionnaire. Face and
content validity were increased by using different ques-
tions to elicit the same information.

A hypothetical case study was used to retest themes of
study design and funding choices. The case study involved
a patient with cirrhosis and hepatitis C who had not
responded to standard pegylated interferon and ribavirin
and was given three treatment options. Treatment option
A involved a long-term clinical trial (5 years) of combina-
tion antiviral therapy (interferon and ribavirin) in varying
doses designed to halt the progression of fibrosis. The trial
was sponsored by a government institution with funding
to cover the cost of the drug without reimbursement for
additional costs. Treatment option B was an oral antiviral
agent in phase 2 of investigation, given for a period of 6
months, and sponsored by a pharmaceutical company
that funded all trial costs. Treatment option C was a 12-
month trial of an intravenous antifibrotic agent in phase
3 of investigation, administered in varying doses includ-
ing a nontreatment arm, and sponsored by a biotechnol-
ogy company that funded all trial costs, including
additional funds for support staff

With the permission of the American Association for the
Study of Liver Diseases (AASLD) executive, we obtained a
register of physician members of the AASLD who had pre-
viously given consent to allow disclosure of their names to
researchers. We mailed the questionnaire to all of these
members (N = 1050). A second mailing to all registry
members was conducted 12 weeks later to increase the
response rate. Respondents could return the question-
naire by mail, fax, or e-mail, and they received no incen-
tive for participation. This study was approved by the
institutional review board of the Duke University Health
System.

Descriptive characteristics of the respondents, preferences
regarding clinical trial participation, funding, and patient
enrollment, and responses to a patient case study and clin-
ical trial scenarios were calculated as percentages of the
total responses in each category. Differences between gas-
troenterologists and hepatologists, clinical researchers
and non-clinical researchers, and physicians with limited
and extensive clinical trial experience were also evaluated.
Respondents who reported spending a nonzero amount


Page 2 of 11
(page number not for citation purposes)


BMC Health Services Research 2008, 8:208








http://www.biomedcentral.com/1472-6963/8/208


of professional time on clinical research activities were
considered to be clinical researchers. Extensive clinical
trial experience was defined as participating in 5 or more
clinical trials during the last 12 months. We used z2 tests
or Fisher exact tests to make comparisons among groups,
with P _< .05 considered statistically significant.

Data from completed questionnaires were entered into a
Microsoft Access database and analyzed using SAS soft-
ware (SAS version 8.02, Cary, North Carolina, USA).


Table I: Characteristics of survey respondents (N = 384)*


Results
Characteristics of the 384 survey respondents (response
rate, 37%) are shown in Table 1. Fifty percent of respond-
ents practiced principally as hepatologists, and 42% prac-
ticed principally as gastroenterologists with an interest in
hepatology. The majority of respondents (71.6%)
reported involvement in research activities, over half
(57.6%) reported involvement with clinical research, and
89.5% of these respondents reported clinical activities.
Similarly, of those reporting involvement in clinical activ-


Characteristic

Male
Race/ethnicity
African American
Asian
Caucasian
Hispanic
Other
Age
25 to 30 years
31 to 40 years
41 to 55 years
56 to 70 years
> 70 years
Specialty
Gastroenterology
Hepatology
Other
Degree
MD or equivalent
MD and PhD
Other
Years in practice
< 5 years
6 to 10 years
I I to 20 years
> 20 years
Practice
Primary care
Tertiary care/academic facility
Community hospital
Private practice
Other
Professional activities:
Basic research
Clinical research
Academic research
Academic clinical practice
Private practice
Industry
Other


All Respondents

294 (79.3)


13 (3.6)
68 (19.1)
241 (67.5)
19 (5.3)
16 (4.5)

II (2.9)
99 (26.2)
212 (56.1)
54(14.3)
2 (0.5)

160 (41.7)
189 (49.2)
29 (7.6)

343 (89.6)
39(10.2)
I (0.3)

48(13.3)
91 (25.3)
139 (38.6)
82 (22.8)

13 (3.7)
214 (60.8)
15 (4.3)
98 (27.8)
12 (3.4)

73 (19.0)
221 (56.7)
I 15 (29.9)
228 (59.4)
166 (43.2)
19 (4.9)
34 (8.9)


Gastroenterologists

128 (83.7)t

4 (2.7)
29(19.3)
101 (67.3)
11 (7.3)
5 (3.3)

6 (3.8)
44 (28.0)
76 (48.4)
29(18.5)
2 (1.3)


149 (93.1)
10 (6.3)
I (0.6)

26 (17.7)t
36 (24.5)
39 (26.5)t
46 (31.3)t

6 (4.1)
73 (50.0)f
I I (7.5)t
52 (35.6)
4 (2.7)

28(17.5)
86 (53.8)t
31 (19.4)t
97 (60.6)
86 (53.8)
5 (3.1)
16(10.0)


* Values are expressed as number (percentage) unless otherwise indicated. Some categories do not sum to 100% because of incomplete data. Of
the 384 respondents, 349 identified their specialty as gastroenterology or hepatology, I as infectious disease, 2 as internal medicine, and 26 as
other. Data were missing for 6 respondents.
t P < .05 for the comparison between specialties.
* Respondents could select more than I activity.


Page 3 of 11
(page number not for citation purposes)


Hepatologists

138 (75.0)t

9 (5.0)
34(19.0)
124 (69.3)
4 (2.2)
8 (4.5)

3 (1.6)
55 (29.4)
108 (57.8)
21 (I 1.2)
0 (0.0)


169 (89.4)
20(10.6)
0 (0.0)

17 (9.3)t
45 (24.7)
89 (48.9)f
31 (1 7.0)

7 (3.9)
I 19 (66.9)t
3 (1.7)t
45 (25.3)
4 (2.3)

31 (16.4)
I 16 (61.4)t
71 (37.6)]
107 (56.6)
72(38.1)
13 (6.9)
13 (6.9)


BMC Health Services Research 2008, 8:208








http://www.biomedcentral.com/1472-6963/8/208


ities (academic or private practice), 70.1% also reported
research activities.

Respondents' experience with clinical trials is summarized
in Table 2. Hepatologists were significantly more likely
than gastroenterologists to report participation as an
investigator in a clinical trial during the past 12 months
(74.6% vs 59.4%; P < .01) and over the past 5 years
(82.0% vs 72.5%; P < .05). Both gastroenterologists
(67%) and hepatologists (76%) received the majority of
their research funding from pharmaceutical companies;
however, hepatologists had received more funding from
universities/hospitals, government, and charitable organ-
izations than gastroenterologists. Gastroenterologists
selected pharmaceutical companies and government
funding equally as their preferred source of funding,
whereas hepatologists showed a clear preference for
industry funding.

Table 3 shows factors influencing physician participation
in clinical research by specialty and for clinical researchers
and non-clinical researchers. Nearly 90% of all respond-


ents cited level of funding or compensation commensu-
rate with the time and effort associated with the clinical
trial as extremely or very important in influencing the
decision to participate. Other important considerations
influencing participation in clinical research included
intellectual pursuit and easy access to clinical trials. Hepa-
tologists were especially likely to cite adequate funding or
compensation levels (92.6% vs 85.0%; P < .05) and offers
by sponsors to fund additional projects as influential fac-
tors (76.2% vs 65.6%; P < .05), compared with gastroen-
terologists. Clinical researchers were significantly more
likely than non-clinical researchers to report sponsor-
funded research (75.5% vs 66.1%; P = .05), peer recom-
mendations (55.2% vs 38.0%; P < .001), and industry
marketing (42.9% vs 11.8%; P < .0001) influenced their
participation in clinical trials.

Table 4 reports barriers to clinical research participation
by specialty and for clinical researchers and non-clinical
researchers. Over half of all respondents reported that
excessive (uncompensated) research costs completely pre-
vented participation in clinical research. About 40%


Table 2: Experience with clinical therapeutic trials among gastroenterologists and hepatologists*


Experience


Gastroenterologists (n = 160)


Number of clinical trials in the previous 12 months
0
I to 4
5 to 10
> 10
Number of clinical trials in the previous 5 years
0
I to 4
5 to 10
> 10
Types of clinical trials
Drug trials (human studies)
Basic science research
Non-drug trials (eg, procedural)
Non-drug epidemiological research
Other
Sources of funding for clinical trials
Pharmaceutical company
Government institutions
Nongovernmental, charitable, or philanthropic organization
University or hospital funding
Other
Most preferred funding source
Pharmaceutical company
Government institution
Nongovernmental, charitable, or philanthropic organization
University or hospital funding
Other


65 (40.6)*
70 (43.8)
17 (10.6)*
7 (4.4)

44 (27.5)*
40 (25.0)
35 (21.9)
40 (25.0)*

1 12(42.9)
28 (17.5)t
39 (24.4)
51 (31.9)t
1 (0.6)

107 (66.9)*
54 (33.8)*
15 (9.4)t
55 (34.4)t
I (0.6)

52 (44.8)
46 (41.1)
13 (12.2)
7 (6.4)
0 (0.0)


Hepatologists (n = 189)


48 (25.4)*
89(47.1)
43 (22.8)*
8 (4.2)

34 (18.0)*
34(18.0)
42 (22.2)
79 (41.8)$

149 (57.1)
51 (27.0)t
53 (28.0)
102 (54.0)*
3 (1.6)

144 (76.2)*
96 (50.8)*
49 (25.9)*
92 (48.7)*
2 (1.1)

79(50.1)
59 (37.8)
10 (7.0)
12 (8.1)
1 (3.2)


* Values are expressed as number (percentage) unless otherwise indicated. Responses refer to clinical studies in which the respondent participated
as an investigator.
t Indicates respondents who reported "most preferred" for each funding source.
* P < .05 for the comparison between specialties.


Page 4 of 11
(page number not for citation purposes)


BMC Health Services Research 2008, 8:208








http://www.biomedcentral.com/1472-6963/8/208


Table 3: Factors influencing participation in clinical trials, by specialty and current participation in clinical research*


Clinical Research Participation


Gastroenterology (n = I60) Hepatology (n = 189)


Clinical Researchers
(n = 221)


Non-Clinical Researchers
(n= 163)


Easy access to clinical trials or
therapy
Level of funding or
compensation for time and
effort
Relationship with institution
conducting the trial
Additional funding offers from
sponsors
Recommendation from peers
Industry marketing
Intellectual pursuit


142 (88.8)t

136 (85.0)t


121 (75.6)

105 (65.6)t

90 (56.3)t
43 (26.9)
135 (84.4)


152 (80.4)t

175 (92.6)t


142 (75.1)

144 (76.2)t

71 (37.6)t
44 (23.3)
172 (91.0)


181 (81.9)

196 (88.7)


163 (73.8)

146 (66. )t

84 (38.0)t
26 (1 1.8)t
191 (86.4)


* Values are expressed as number (percentage) responding "extremely important" or "very important.
t P < .05 for the comparison between specialties or between clinical and non-clinical researchers.


reported that excess costs were of concern but did not pre-
vent participation. In addition, 35.7% of physicians
reported that lack of specialized support staff prevented
them from participating in clinical research. Respondents
who were not involved in clinical research were more than
twice as likely as those who were involved to report lack
of specialized support staff as a barrier to clinical trial par-
ticipation (49.1% vs 23.5%; P < .001). Respondents were
also concerned about the complexity of institutional


review board (IRB) requirements and ethical considera-
tions. Although few respondents reported that IRB
requirements completely prevented them from participat-
ing in clinical trials, 68.7% of gastroenterologists and
74.3% of hepatologists listed IRB requirements as a con-
cern.

One-fourth of all respondents reported that ethical con-
siderations completely prevented them from participating


Table 4: Factors preventing clinical trial participation, by specialty and current participation in clinical research*


Clinical Research Participation


Gastroenterology (n = I60) Hepatology (n = 189)


Clinical Researchers
(n =221)


Non-Clinical Researchers
(n= 163)


Increasing complexity of trials
Excessive trial costs not
covered by the trial sponsor
Complexity of Institutional
Review Board requirements
Inferior trial medications)
compared to standard therapy
Lack of specialized support
staff
Concern about sponsor
control of trial decision-
making, data, publication, etc
Too busy with clinical practice
commitments
Ethical considerations
Difficulty in accessing the
appropriate patient
population
Not interested in participating
in sponsored clinical research


12 (8.1)
76 (50.7)

20 (13.3)

65 (43.3)

50 (32.9)

22(14.8)


37 (24.3)

41 (27.2)
15 (9.9)


14 (9.4)t


10(5.4)
98 (52.7)

10(5.4)

86 (46.0)

71 (38.0)

37(19.9)


46 (24.7)

45 (24.1)
18 (9.6)


22 (I 1.9)


10 (4.7)
1 15 (54.5)t

18(8.5)

I 15 (54.0)t

52 (24.4)t

54 (25.6)t


14 (6.6)t

70 (32.9)t
25 (11.7)t


13 (8.4)
73 (46.5)

15 (9.6)

54 (34.6)

80 (50.6)

18 (1 1.5)


74 (46.8)

26(16.6)
13 (8.3)


32 (20.5)


* Values are expressed as number (percentage) responding "completely prevents me [from participating]."
t P < .05 for the comparison between specialties or between clinical and non-clinical researchers.


Page 5 of 11
(page number not for citation purposes)


Factor


Specialty


140 (85.9)

143 (87.7)


123 (75.5)

123 (75.5)t

90 (55.2)t
70 (42.9)t
146 (89.6)


Factor


Specialty


BMC Health Services Research 2008, 8:208







http://www.biomedcentral.com/1472-6963/8/208


in clinical trials, and nearly half (49.1%) said they were
concerned about trial ethics. As might be expected, a sub-
stantial majority of responding physicians (80.7%) were
concerned about the inferiority of study medications
compared to standards of care. Many respondents
(62.4%) were concerned about sponsor control, and
17.6% of all responding physicians reported that concerns
about sponsor control of decision making, data, and/or
publication completely prevented them from participat-
ing in clinical research. Interestingly, clinical researchers
were more likely to report concerns about study medica-
tions (52.0% vs 33.1%; P < .001) and sponsor control
(24.4% vs 11.0%; P < .001) as barriers to clinical trial par-
ticipation, compared to respondents who were not
involved in clinical research. Barriers to clinical trial par-
ticipation were similar for both highly experienced and
less experienced clinical researchers, although the former


were more likely to cite concerns about study medications
as a barrier (64.5% vs 47.2%; P = .02). Finally, a quarter
of all respondents and 45.4% of those not involved in
clinical research reported that clinical practice commit-
ments did not leave enough time to participate in clinical
studies.

The perceived ability of the patient to comply with, adhere
to, and comprehend protocols was cited by at least 90%
of all respondents as extremely or very important in influ-
encing the decision to enroll patients in clinical trials.
Cost considerations, either to the patient or the physician,
were also frequently cited as factors influencing enroll-
ment. A minority of physicians were likely to enroll
patients with high-risk characteristics such as older age,
advanced disease, or lack of insurance in clinical trials
(Figure 1). Gastroenterologists were more likely than


Patients aged > 65 years



Patients with advanced
disease



Unemployed patients



Uninsured patients



Non-English-speaking patients



Patients with low literacy or
numeracy


0% 5% 10% 15% 20% 25% 30% 35% 40%






Figure I
Proportion of respondents very likely to enroll patients in clinical research by patient characteristics.




Page 6 of 11
(page number not for citation purposes)


BMC Health Services Research 2008, 8:208








http://www.biomedcentral.com/1472-6963/8/208


hepatologists to cite logistical considerations (55% vs
43.9%; P < .05) and cost to the patient (85.6% vs 76.2%;
P < .05) as affecting patient enrollment decisions.

Respondents' interest in trials with specific characteristics
is summarized in Table 5. Overall, respondents were most
interested in shorter trials (duration less than 2 years) and
phase 3 trials. Less than half of the respondents reported
a preference for phase 2 or phase 4 trials, and fewer than
one-third were very interested in phase 1 studies. Interest
in longer trials and in placebo-controlled trials or trials
with nontreatment arms was low. Only 1 in 5 respondents
reported interest in trials involving multiple treatment
arms and/or crossover designs or trials involving invasive
procedures.

Physician interest in participating in various types of clin-
ical studies was strongly associated with specialty and
clinical trial experience. Hepatologists were more inter-
ested than gastroenterologists in participating in phase 1
studies (38.6% vs 22.5%; P < .001) and phase 2 studies
(56.6% vs 40%; P < .01). However, gastroenterologists
were more interested than hepatologists in phase 4 studies
(47.5% vs 36.0%; P < .05). Phase 3 studies appeared to be
the most desired phase of study among both gastroenter-
ologists and hepatologists. These preferences were similar
among experienced clinical researchers compared to less
experienced researchers.

Results from the hypothetical patient enrollment scenar-
ios (Figure 2) are consistent with preferences for shorter
trials and concerns about funding noted above. Signifi-
cantly fewer respondents reported that they would be very


or somewhat likely to enroll the patient into trial A, com-
pared to trials B and C (65.6% vs 88.8% vs 87.8%; respec-
tively; P < .001). This pattern was consistent across
specialty, current participation in clinical research, and
clinical trial experience.

Discussion
Previous work examining physician participation in clini-
cal research has focused for the most part on oncology,
internal medicine, and general practice [3,7,13-17]. In
this study, we explored hepatologists' and gastroenterolo-
gists' perceptions of barriers to clinical investigation in the
current practice environment. The majority of respond-
ents were involved in research activities and indicated
intellectual pursuit as an important factor in influencing
participation in research. However, regardless of the level
of clinical trial experience, respondents cited issues with
resources as barriers to participation in clinical research,
including financial compensation, IRB support, availabil-
ity of specialized support staff, and the complexity of clin-
ical trials. This lack of support for core research
infrastructure was reflected in concerns about ability to
cover the total costs of clinical research in an increasingly
resource-constrained practice environment.

Other physician specialists, particularly oncologists, have
identified the same barriers to clinical trial participation
cited by gastroenterologists and hepatologists in the
present study [3,13-15]. Although one study of breast can-
cer specialists indicated that physicians have become
more amenable to enrolling patients into clinical trials
[14], organizational support and resource costs remained
significant concerns. Our findings suggest that these con-


Table 5: Characteristics of preferred clinical trials*


Characteristic


Specialty


Experience


Gastroenterology (n = 160) Hepatology (n = 189)


Less Experienced
Researchers (n = I 59)


More Experienced
Researchers (n = 62)


Phase I trials
Phase 2 trials
Phase 3 trials
Phase 4 trials
Duration < 2 years
Duration > 2 years
Trials with placebo or no
treatment arm
Trials involving invasive
procedures
Multiple-arm and crossover
protocols
Industry funding
Government funding
Non-government funding


36 (22.5)t
64 (40.0)t
97 (60.6)
76 (47.5)t
100 (62.5)
38 (23.8)
51 (31.9)

40 (25.0)t

36 (22.5)

76 (47.5)
78 (48.8)t
78 (48.8)


73 (38.6)t
107 (56.6)t
108 (57.1)
68 (36.0)t
126 (66.7)
59 (31.2)
55 (29.1)

30 (15.9)t

35 (18.5)

104 (55.0)
121 (64.0)t
103 (54.5)


59 (37.1)t
91 (57.2)t
114 (71.7)t
92 (57.9)
127 (79.9)t
57 (35.9)t
68 (42.8)

44 (27.7)

40 (25.2)t

86 (54.1) )
104 (65.4)t-
96 (60.4)f


32 (51.6)t
52 (83.9)t
53 (85.5)t
28 (45.2)
58 (93.6)t
35 (56.5)]
28 (45.2)

18(29.0)

24 (38.7)

50 (80.7)f
56 (90.3)]
51 (82.3)]


* Values are expressed as number (percentage) responding "very interested".
t P < .05 for the comparison between specialties or between clinical and non-clinical researchers.


Page 7 of 11
(page number not for citation purposes)


BMC Health Services Research 2008, 8:208







http://www.biomedcentral.com/1472-6963/8/208


70%


I Not at all likely U Somewhat likely


MVery likely


0% 1
Trial A


Figure 2
Responses to the patient case study.


cerns are not limited to oncology, thus inviting specula-
tion that the same factors might apply to other physician
specialists. However, given the paucity of related research
in other specialties and the limitations of existing studies,
definitive conclusions about barriers to clinical trial par-
ticipation across specialties are difficult to make.

Clinical research is the cornerstone of evidence-based
medical practice and the key translational step from basic
science discovery to benefits for individual patients. This
survey, the largest of its kind in this field, illustrates the
interest in clinical research among members of the
AASLD. However, it also describes some worrisome trends
where physicians preferred participation in typical short-
term clinical trials over more definitive trial designs and
participation was influenced by the level of payment.
Hepatologists in particular showed a clear preference for


industry funding. Hepatologists were also more likely to
have participated in a clinical trial over the preceding 5
years, and their responses may reflect the realities of con-
ducting research in the current climate, in which govern-
ment funding is in decline and the reimbursement linked
to industry-sponsored trials has become crucial to the
maintenance of research programs [8,9]. A review of
industry funding in gastrointestinal clinical research con-
firms that industry sponsorship of research is increasing
and, therefore, will continue to determine the research
agenda [12].

Hepatologists' greater participation in clinical trials and
their preference for industry-sponsored studies also may
reflect a broader dynamic related to the structure of physi-
cian compensation. In the United States, reimbursement
for many medical procedures has been relatively higher -


Page 8 of 11
(page number not for citation purposes)


I Not sure


Trial B


Trial C


BMC Health Services Research 2008, 8:208







http://www.biomedcentral.com/1472-6963/8/208


on an hourly basis than for evaluation and management
services [18,19], though that gap has been reduced by
changes in the Medicare fee schedule over time [20]. If
reimbursement levels in hepatology where the focus is
less procedural than for gastroenterology as a whole are
inadequate to support physician practices, hepatologists
may feel pressured to participate in industry-sponsored
clinical trials as a means of supplementing their practice
income and/or supporting academic salaries.

Anecdotal evidence suggests that another possible expla-
nation for the greater participation of hepatologists in
clinical trials is that gastroenterologists, in general, have
been more exposed to device-oriented research and its
marketing, which has remained relatively constant during
the past decade. In contrast, hepatologists have been
exposed to many new companies, sponsors, and trials for
hepatitis and other liver diseases during this time, partic-
ularly during the past 5 to 10 years. Thus, hepatologists'
exposure to, and requests to participate in, clinical studies
may have been greater, and perhaps their incentives
higher, than those for gastroenterologists.

Although industry sponsorship was the respondents' pre-
ferred source of funding, relationships with sponsors,
especially regarding sponsor control over trial decision
making, data, and/or publication, were a major concern,
reflecting ongoing explorations of the means of assuring
transparency in reporting the results of clinical research.
Less experienced investigators, in particular, were more
likely to be influenced by industry marketing when con-
sidering competing research opportunities. Encourag-
ingly, a recent review of gastrointestinal research
publications reported that, on average, industry-spon-
sored studies were of superior methodologic quality to
studies funded by other sources and were no more likely
than other studies to publish results that favored the study
sponsor, although an extremely high percentage of all
studies in these journals reported positive results [12].

This study has some limitations. Our findings may not be
representative of all gastroenterologists and hepatologists
eligible to conduct clinical research in the United States.
We targeted members of the AASLD under the assumption
that most gastroenterologists and hepatologists with an
interest in clinical research likely would be associated with
the organization. It is reasonable to expect that physicians
who perceive high barriers to participation in such activi-
ties would be less likely to join professional, research-
focused organizations. Thus, our focus on AASLD mem-
bers may have introduced a bias toward those facing fewer
barriers to clinical research participation. In that sense, the
results of our study may be interpreted as a conservative
estimate of barriers to the conduct of clinical research in
the United States.


Previous participation as an investigator in clinical studies
was not a prerequisite for survey participation. Limiting
our sample only to physicians with current or previous
participation in clinical research, as other surveys have
done [151, also may have introduced a bias into the study.
Further, our definition of clinical research experience was
based on respondents' self-reports of participation and
did not consider whether respondents accrued patients to
those studies in which they agreed to participate. It is pos-
sible that physicians who agree to participate in clinical
trials but do not accrue patients may perceive (and report)
barriers to clinical research differently than those with
greater enrollment success. These participants were more
likely to be involved in research activity as opposed to non
members, thereby creating an additional bias.

Within the AASLD membership, only members who had
previously given consent to allow disclosure of their
names to researchers were contacted for participation in
this study; this also may have introduced bias. Moreover,
not all AASLD members in the target population com-
pleted the survey. The overall response rate was compara-
tive to other mail surveys of physicians and other health
care professionals and perhaps could have been improved
through the use of an incentive [21-271. Finally, our sur-
vey may not have captured all aspects of clinical trial par-
ticipation relevant to gastroenterologists and
hepatologists.

Conclusion
This study suggests that the greatest barrier to participa-
tion in clinical research is a lack of adequate resources,
which most likely influenced the preference for less com-
plex trial protocols and studies of relatively short dura-
tion. The findings of the study also reflect the reality of
industry sponsorship of much clinical investigation in
gastroenterology and hepatology and highlight some of
the critical gaps in the clinical research infrastructure [28]
that may ultimately limit the expansion of evidence-based
clinical practice and translational research. One way to
close gaps in the research infrastructure is for large institu-
tions (and perhaps smaller ones) to create centralized
research support services. Though challenging to imple-
ment at a reasonable cost, such services may provide a
more effective research environment that will improve
patient safety, increase economic and medical efficiency,
and provide a more standardized and regulatory-compli-
ant process for conducting research.

Abbreviations
AAMC: Association of American Medical Colleges;
AASLD: American Association for the Study of Liver Dis-
eases; IRB: institutional review board.




Page 9 of 11
(page number not for citation purposes)


BMC Health Services Research 2008, 8:208








http://www.biomedcentral.com/1472-6963/8/208


Competing interests
Drs Schulman and McHutchison have received grants
and/or consultancy fees from a number of private organi-
zations. They have made available online detailed listings
of financial disclosures http://www.dcri duke edu/
research/coi.jsp. All other authors declare that they have
no competing interests.

Authors' contributions
ATD and TLK conceived and designed the study, acquired
the data, analyzed and interpreted the data, and drafted
the manuscript. AZ designed the study, acquired the data,
analyzed and interpreted the data, and revised the manu-
script for important intellectual content. KP designed the
study, acquired the data, analyzed and interpreted the
data, and revised the manuscript for important intellec-
tual content. KH acquired the data, analyzed and inter-
preted the data, and revised the manuscript for important
intellectual content. KAS conceived and designed the
study, analyzed and interpreted the data, and revised the
manuscript for important intellectual content. JGM con-
ceived and designed the study, analyzed and interpreted
the data, revised the manuscript for important intellectual
content, and supervised the study. All authors read and
approved the final manuscript.

Additional contributions
We thank Damon Seils of Duke University for assistance
with manuscript preparation. Mr Seils did not receive
compensation for his assistance apart from his employ-
ment at the institution where the study was conducted.

Additional material


Additional file 1
Survey of involvement and participation in clinical trials. The ques-
tionnaire administered to study participants.
Click here for file
[http://www.biomedcentral.com/content/supplementary/1472-
6963-8-208-S1.pdf]


Acknowledgements
Funding/support

None.

References
I. Thomas PA, Diener-West M, Canto Ml, Martin DR, Post WS, Streiff
MB: Results of an academic promotion and career path sur-
vey of faculty at the Johns Hopkins University School of Med-
icine. Acad Med 2004, 79:258-264.
2. Prescott RJ, Counsell CE, Gillespie WJ, Grant AM, Russell IT, Kiauka
S, Colthart IR, Ross S, Shepherd SM, Russell D: Factors that limit
the quality, number and progress of randomised controlled
trials. Health Technol Assess 1999, 3:1-143.
3. Mansour EG: Barriers to clinical trials. Part III: Knowledge and
attitudes of health care providers. Cancer 1994, 74:2672-2675.


4. Centre for Reviews and Dissemination: Systematic review of barriers,
modifiers and benefits involved in participation in cancer clinical trials. York,
United Kingdom 2006.
5. Association of American Medical Colleges: Breaking the Scientific Bot-
tleneck Clinical Research: A National Call to Action. Washington, DC
1999.
6. Keinonen T, Keranen T, Klaukka T, Saano V, Ylitalo P, Enlund H:
Investigator barriers and preferences to conduct clinical
drug trials in Finland: a qualitative study. Pharm World Sci 2003,
25:251-259.
7. Ashar BH, Miller RG, Getz KJ, Powe NR: Prevalence and determi-
nants of physician participation in conducting pharmaceuti-
cal-sponsored clinical trials and lectures. j Gen Intern Med 2004,
19:1140-1145.
8. Moses H III, Dorsey ER, Matheson DH, Thier SO: Financial anat-
omy of biomedical research. JAMA 2005, 294:1333-1342.
9. Blumenthal D: Academic-industrial relationships in the life sci-
ences. N Engl j Med 2003, 349:2452-2459.
10. Blumenthal D, Campbell EG, Causino N, Louis KS: Participation of
life-science faculty in research relationships with industry. N
Englj Med 1996, 335:1734-1739.
I I. Lloyd T, Phillips BR, Aber RC: Factors that influence doctors'
participation in clinical research. Med Educ 2004, 38:848-851.
12. Brown A, Kraft D, Schmitz SM, Sharpless V, Martin C, Shah R,
Shaheen NJ: Association of industry sponsorship to published
outcomes in gastrointestinal clinical research. Clin Gastroen-
terol Hepatol 2006, 4:1445-1451.
13. Somkin CP, Altschuler A, Ackerson L, Geiger AM, Greene SM,
Mouchawar J, Holup J, Fehrenbacher L, Nelson A, Glass A, et al.:
Organizational barriers to physician participation in cancer
clinical trials. Am j Manag Care 2005, 11:413-421.
14. Melisko ME, Hassin F, Metzroth L, Moore DH, Brown B, Patel K, Rugo
HS, Tripathy D: Patient and physician attitudes toward breast
cancer clinical trials: developing interventions based on
understanding barriers. Clin Breast Cancer 2005, 6:45-54.
15. Rahman M, Morita S, Fukui T, Sakamoto J: Physicians' attitudes
towards and reasons for participation in the Candesartan
Antihypertensive Survival Evaluation in Japan (CASE-J) trial.
j Epidemiol 2005, I 5:38-40.
16. Franke L, Kommers T, Van WE, Lucasson P, Beek M, Van den HH,
Van WC: General practice registrars and research attitudes
toward participation. Aust Fam Physician 2008, 37:276-279.
17. Hummers-Pradier E, Scheidt-Nave C, Martin H, Heinemann S,
Kochen MM, Himmel W: Simply no time? Barriers to GPs' par-
ticipation in primary health care research. Fam Pract 2008,
25:105-112.
18. Hsiao WC, Couch NP, Causino N, Becker ER, Ketcham TR, Verrilli
DK: Resource-based relative values for invasive procedures
performed by eight surgical specialties. JAMA 1988,
260:2418-2424.
19. Murphy TP: American College of Radiology Practice Guide-
line for Interventional Clinical Practice: a commitment to
patient care. j Vasc Interv Radiol 2005, 16:157-159.
20. Lotan Y, Cadeddu JA, Roehrborn CG, Stage KH: The value of your
time: evaluation of effects of changes in medicare reim-
bursement rates on the practice of urology. J Urol 2004,
172:1958-1962.
21. Abourjaily P, Gouveia WA, Selker HP, Zucker DR: Evaluating the
nondrug costs of formulary coverage restrictions. Manag Care
2005, 14:50-7. 62.
22. Stone DU, Butt AL, Chodosh J: Ocular surface squamous neopla-
sia: a standard of care survey. Cornea 2005, 24:297-300.
23. Jepson C, Asch DA, Hershey JC, Ubel PA: In a mailed physician
survey, questionnaire length had a threshold effect on
response rate. j Clin Epidemiol 2005, 58:103-105.
24. Szilagyi PG, Shone LP, Barth R, Kouides RW, Long C, Humiston SG,
Jennings J, Bennett NM: Physician practices and attitudes
regarding adult immunizations. Prev Med 2005, 40:152-161.
25. Delnevo CD, Abatemarco DJ, Steinberg MB: Physician response
rates to a mail survey by specialty and timing of incentive.
Am j Prey Med 2004, 26:234-236.
26. Schneider SM, Gallery ME, Schafermeyer R, Zwemer FL: Emergency
department crowding: a point in time. Ann Emerg Med 2003,
42:167-172.


Page 10 of 11
(page number not for citation purposes)


BMC Health Services Research 2008, 8:208








http://www.biomedcentral.com/1472-6963/8/208


27. Baron G, De WP, Milord F: Cost-effectiveness of a lottery for
increasing physicians' responses to a mail survey. Eval Health
Prof 2001, 24:47-52.
28. Zerhouni EA: Translational and clinical science time for a
new vision. N Englj Med 2005, 353:1621 -1623.

Pre-publication history
The pre-publication history for this paper can be accessed
here:

httn-//Nww hinmPedrntral cmm/1 477-Ac)AR/?)OR/nrP


Page 11 of 11
(page number not for citation purposes)


Publish with BioMed Central and every
scientist can read your work free of charge
"BioMed Central will be the most significant development for
disseminating the results of biomedical research in our lifetime."
Sir Paul Nurse, Cancer Research UK
Your research papers will be:
available free of charge to the entire biomedical community
peer reviewed and published immediately upon acceptance
cited in PubMed and archived on PubMed Central
yours you keep the copyright
Submit your manuscript here: BioMedcentral
http://www.biomedcentral.com/info/publishing adv.asp


BMC Health Services Research 2008, 8:208




University of Florida Home Page
© 2004 - 2010 University of Florida George A. Smathers Libraries.
All rights reserved.

Acceptable Use, Copyright, and Disclaimer Statement
Last updated October 10, 2010 - - mvs