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Original Investigation | Health Policy

Testing Practices, Interpretation, and Diagnostic Evaluation


of Iron Deficiency Anemia by US Primary Care Physicians
Andrew J. Read, MD, MS; Akbar K. Waljee, MD, MS; Jeremy B. Sussman, MD, MS; Hardeep Singh, MD, MPH; Grace Y. Chen, MD, PhD;
Sandeep Vijan, MD, MS; Sameer D. Saini, MD, MS

Abstract Key Points


Question How do US primary care
IMPORTANCE Recognition of iron deficiency anemia (IDA) is important to initiate timely evaluation
physicians approach testing for anemia,
for gastrointestinal tract cancer. Retrospective studies have reported delays in diagnostic evaluation
interpretation of iron studies, and
of IDA as a common factor associated with delayed diagnosis of colorectal cancer.
diagnostic evaluation for iron
deficiency anemia?
OBJECTIVE To assess how US primary care physicians (PCPs) approach testing for anemia, interpret
iron laboratory studies, and refer patients with IDA for gastrointestinal endoscopy. Findings In this survey study of 325 US
primary care physicians, 76.9% of
DESIGN, SETTING, AND PARTICIPANTS This survey study, conducted in August 2019, included respondents self-reported screening
members of the American College of Physicians Internal Medicine Insiders Panel, a nationally patients for anemia, 73.5% correctly
representative group of American College of Physicians membership, who self-identified as PCPs. diagnosed iron deficiency anemia, and
Participants completed a vignette-based survey to assess practices related to screening for anemia, 54.5% recommended bidirectional
interpretation of laboratory-based iron studies, and appropriate diagnostic evaluation of IDA. endoscopy for new-onset iron
deficiency anemia among women aged
MAIN OUTCOMES AND MEASURES Descriptive statistics based on survey responses were 65 years (55.1% for men aged 65 years).
evaluated for frequency of anemia screening, correct interpretation of iron laboratory studies, and
Meaning Screening for anemia was
proportion of patients with new-onset IDA referred for gastrointestinal tract evaluation.
commonly self-reported by primary care
physicians despite the absence of
RESULTS Of 631 PCPs who received an invitation to participate in the survey, 356 (56.4%)
guidelines recommending routine
responded and 31 (4.9%) were excluded, for an adjusted eligible sample size of 600, yielding 325
anemia screening, and bidirectional
completed surveys (response rate, 54.2%). Of the 325 participants who completed surveys, 180
endoscopy was underused to evaluate
(55.4%) were men; age of participants was not assessed. The mean (SD) duration of clinical
new-onset iron deficiency anemia.
experience was 19.8 (11.2) years (range, 1.0-45.0 years). A total of 250 participants (76.9%) screened
at least some patients for anemia. Interpretation of iron studies was least accurate in a scenario of a
borderline low ferritin level (40 ng/mL) with low transferrin saturation (2%); 86 participants (26.5%) + Supplemental content
incorrectly responded that this scenario did not indicate IDA, and 239 (73.5%) correctly identified Author affiliations and article information are
this scenario as IDA. Of 312 participants, 170 (54.5%) recommended bidirectional endoscopy (upper listed at the end of this article.

endoscopy and colonoscopy) for new IDA for women aged 65 years; of 305 respondents, 168 (55.1%)
recommended bidirectional endoscopy for men aged 65 years.

CONCLUSIONS AND RELEVANCE In this survey study, US PCPs’ self-reported testing practices for
anemia suggest overuse of screening laboratory tests, misinterpretation of iron studies, and
underuse of bidirectional endoscopy for evaluation of new-onset IDA. Both misinterpretation of iron
studies and underuse of bidirectional endoscopy can lead to delayed diagnosis of gastrointestinal
tract cancers and warrant additional interventions.

JAMA Network Open. 2021;4(10):e2127827. doi:10.1001/jamanetworkopen.2021.27827

Open Access. This is an open access article distributed under the terms of the CC-BY License.

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JAMA Network Open | Health Policy Diagnostic Testing and Evaluation of Iron Deficiency Anemia by US PCPs

Introduction
Iron deficiency anemia (IDA) is a classic early diagnostic sign of gastrointestinal (GI) tract malignant
neoplasm.1,2 Between 1% and 10% of adult patients with IDA may have undiagnosed GI tract
cancer.3,4 Prompt and thorough evaluation of IDA is essential. However, retrospective studies have
reported that delays in diagnostic evaluation of IDA are common5,6 and can lead to a delayed
diagnosis of colorectal cancer.7,8 This problem is of increasing importance given the increasing
incidence of colorectal cancer among younger patients outside the age range for which routine
colorectal cancer screening is recommended, for whom IDA may be the first diagnostic sign of
malignant neoplasm.9,10
Clinical practices related to identification and evaluation of IDA likely vary substantially, with at
least 30 different guidelines from 10 specialty societies.11-14 However, variation related to testing
practices, interpretation of laboratory test results, and diagnostic evaluation of IDA among physicians
is not well studied even though these factors may be associated with diagnostic delays, missed
cancer diagnoses, and low-value care. For instance, because of a low diagnostic yield, anemia
screening is not recommended for adults except during pregnancy, and recommendations about
screening during pregnancy are mixed.15-17 Inappropriate screening may be associated with health
care waste and potential unintended harm (eg, additional downstream diagnostic tests). Inaccurate
test interpretation of iron studies (eg, serum ferritin level and iron saturation) can also lead to medical
error, with misclassification of patients’ iron level. Interpretation can be complicated because the
ferritin level may be elevated in the context of an inflammatory process, potentially masking
underlying iron deficiency.2,18 Guidelines consistently recommend that men with IDA and
postmenopausal women, in the absence of obvious causes, should be evaluated for potential occult
GI tract blood loss with colonoscopy and esophagogastroduodenoscopy (EGD).11,12 However, older
guidelines, which predated the increasing incidence of colorectal cancer among younger patients
observed over the past decade, recommended against initial endoscopic evaluation for
premenopausal women with IDA given the more common cause of iron deficiency secondary to
menstrual blood loss.11 Together, these issues introduce ambiguity and complexity to the evaluation
of IDA.
Our objective was to understand how primary care physicians (PCPs) approach testing and
evaluation of patients for IDA. To do this, we conducted a survey study consisting of a vignette-based
assessment of PCPs to examine their practices related to IDA testing and evaluation for male and
female patients of different ages. A better understanding of current PCP evaluation and referral
patterns for GI endoscopy in the context of IDA may reveal potential opportunities to intervene and
promote earlier diagnosis of GI tract cancers.

Methods
Study Population and Survey Distribution
For this survey study, we conducted a national online survey of internal medicine PCPs in August
2019 using the American College of Physicians (ACP) Internal Medicine Insiders Panel. The ACP
Insiders Panel is a nationally representative group of internal medicine physicians selected through
stratified random sampling as representative of the ACP’s membership as a whole.19 The ACP is the
largest internal medicine specialty organization, with 163 000 members. Potentially eligible
participants (identified as PCPs who had completed training within the ACP Insiders Panel
demographics profile) received an email invitation to complete the electronic survey, and those who
completed the survey received points that could be redeemed for Amazon.com gift cards. Two email
reminders were sent during a 2-week eligibility period. All respondents had to meet the following
inclusion criteria: (1) practice outpatient primary care medicine, (2) practice primarily general internal
medicine and not a subspecialty, and (3) have completed residency training. The study was deemed
exempt from the requirement for informed consent by the University of Michigan institutional review

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JAMA Network Open | Health Policy Diagnostic Testing and Evaluation of Iron Deficiency Anemia by US PCPs

board owing to minimal potential harm related to completion of this survey study because no
patient- or physician-identifiable information was collected. The study followed the American
Association for Public Opinion Research (AAPOR) reporting guideline.

Questionnaire Design
We developed a survey to assess current PCP practices for the testing and evaluation of IDA. Clinical
vignettes provided with the survey questions were used to address 3 sequential domains to elicit
physicians’ clinical practices and decision-making processes20: (1) the practice of obtaining a
complete blood count (CBC) for asymptomatic healthy individuals (ie, screening for anemia), (2) PCP
ordering and interpretation of iron laboratory studies, and (3) evaluation and management of IDA
and referral for GI endoscopy (colonoscopy and/or EGD). For screening, 5 scenarios were used to
understand testing practices for 5 hypothetical asymptomatic individuals presenting as new patients:
a 35-year-old man, a 35-year-old woman (not pregnant), a 35-year-old pregnant woman, a
65-year-old man, and a 65-year-old woman. For interpretation of iron laboratory studies, a series of
4 combinations of ferritin level and transferrin saturation were presented: low transferrin saturation
(6%) and a low ferritin level (11 ng/mL) (to convert to μg/L, multiply by 1.0), normal transferrin
saturation (30%) and normal ferritin level (150 ng/mL), normal transferrin saturation (25%) and low
ferritin level (6 ng/mL), and low transferrin saturation (2%) and normal to low ferritin level (40
ng/mL). Respondents selected whether the scenario represented anemia due to iron deficiency or
another cause.
Four hypothetical patient scenarios were presented for evaluation of management of newly
diagnosed IDA to assess use of EGD and colonoscopy: a 35-year-old man, a 35-year-old woman (not
pregnant), a 65-year-old man, and a 65-year-old woman. We also developed and included 2
questions regarding general attitudes about diagnostic testing: 1 focused on watching and waiting
and 1 focused on laboratory tests and diagnostic procedures.21 The questionnaire included a subset
of questions related to knowledge and application of the 2018 American Cancer Society Colorectal
Cancer Screening Guideline,22 and these questions were analyzed separately.23 The questionnaire
was developed in consultation with a survey development team and iteratively modified based on
feedback from 10 PCPs at the University of Michigan, Ann Arbor. The final version of the
questionnaire is available in the eAppendix in the Supplement.

Statistical Analysis
Survey responses are summarized using proportions, and summary statistics are reported for
continuous variables. A 2-sided P < .05 was considered statistically significant. We used a χ2 test for
analysis of the categorical variables. Statistical analysis was performed using SAS, version 9.4 (SAS
Institute). Graphs were produced using GraphPad Prism, version 8.0 (GraphPad Software).

Results
Respondent Characteristics
The survey was distributed electronically via email invitation to 633 individuals on the ACP Insiders
Panel in August 2019 who met prescreening criteria as PCPs (according to the ACP Insiders Panel
demographics profile); 2 could not be reached. Of 631 PCPs who received an invitation, 356 (56.4%)
responded and 31 (4.9%) were excluded, for an adjusted eligible sample size of 600, yielding 325
completed surveys (response rate, 54.2%). Of the 325 respondents who completed the survey, 180
(55.4%) listed their gender as male and 315 (96.9%) were board certified in internal medicine; age of
respondents was not assessed (Table). Respondents represented a wide variation of clinical practice
experience. Clinical practice duration ranged from 1.0 to 45.0 years (mean [SD], 19.8 [11.2] years);
231 respondents (71.1%) practiced exclusively outpatient primary care, and 120 (36.9%) had an
academic affiliation to a medical school. Of 325 physicians, 303 (93.2%) agreed that too many
laboratory tests and diagnostic procedures are performed in the US health care system.

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Demographic information from the ACP Insiders Panel was analyzed to compare potential
differences between respondents and nonrespondents. Demographic data from August 2019 were
available for 454 of the 633 participants (71.7%) who were invited to complete the survey, including
240 who responded to the survey and 214 who did not respond. There were no statistically
significant differences between respondents and nonrespondents by geographic region (West,

Table. Characteristics of 325 Respondents to the Survey

Characteristic Respondentsa
Time in clinical practice, y
Mean (range) 19.8 (1.0-45.0)
Median (IQR) 20.0 (10.0-29.0)
Region
Urban 129 (39.7)
Suburban 167 (51.4)
Rural 29 (8.9)
Gender
Male 180 (55.4)
Female 131 (40.3)
Prefer not to answer 14 (4.3)
Race and ethnicity
Asian 80 (24.6)
Black or African American 6 (1.9)
White 193 (59.4)
Otherb 7 (2.2)
Prefer not to answer 39 (12.0)
Affiliated with a medical school
Yes 120 (36.9)
No 205 (63.1)
Board-certified in internal medicine
Yes 315 (96.9)
No 10 (3.1)
Practice setting
Single-specialty office 125 (38.5)
Multispecialty office 90 (27.7)
Medical school or academic medical center 34 (10.5)
US governmentc 23 (7.1)
Hospital based 21 (6.5)
Free-standing ambulatory care or urgent care center 10 (3.1)
Institutiond 5 (1.5)
Other 17 (5.2)
Type of practice where most time is spent
All outpatient 231 (71.1)
Primarily outpatient with some inpatient 75 (23.1)
Primarily inpatient with some outpatient 10 (3.1)
Equal outpatient and inpatient 9 (2.8)
General attitudes toward testing
Reluctant to watch and wait 221 (68.0)
Overuse of laboratory tests and diagnostic procedures 303 (93.2)

Abbreviation: IQR, interquartile range.


a
Data are presented as number (percentage) of respondents unless otherwise
indicated.
b
Self-identified as other than the listed choices.
c
Includes Veterans Affairs and military settings.
d
Includes prisons, nursing facilities, and other institutions.

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JAMA Network Open | Health Policy Diagnostic Testing and Evaluation of Iron Deficiency Anemia by US PCPs

Midwest, Northeast, or South), age group (<40 years, 40-55 years, or >55 years), specialty (general
internal medicine, subspecialist, hospitalist, or other), or career stage (graduated medical school >16
years ago or ⱕ16 years ago). Respondents were more likely than nonrespondents to be White than
a member of another racial or ethnic group (race and ethnicity were analyzed as dichotomous
variables as collected by the ACP Insiders Panel team based on participant self-report) (146 of 215
White respondents [67.9%] vs 104 of 195 White nonrespondents [53.3%]; P = .003) and were more
likely than nonrespondents to be male (141 of 236 male respondents with gender data [59.7%] vs
102 of 207 male nonrespondents with gender data [49.3%]; P = .03).

Screening for Anemia


Respondents were asked about their practice of testing asymptomatic healthy patients for anemia by
obtaining CBCs (screening) in a series of hypothetical scenarios involving 35-year-old or 65-year-old
men and women presenting as new patients to their practices. Obtaining screening CBCs was a
common practice among respondents; 250 of 325 physicians (76.9%) reported testing at least some
asymptomatic patients aged 35 years or 65 years (Figure 1). Of 325 PCPs, 159 (48.9%) reported they
would test all these new patients for anemia by obtaining a CBC. Physicians who reported being
generally reluctant to recommend watching and waiting were significantly more likely to recommend
screening all the groups for anemia (odds ratio [OR], 4.23; 95% CI, 2.53-7.07; P < .001). Physicians’
gender, practice region (urban, suburban, or rural), practice type (exclusively outpatient practice vs
some inpatient practice), and stage in clinical practice (<5 years or ⱖ5 years) were not significantly
associated with reporting screening. Physicians for whom the primary practice setting was an
academic medical center were less likely to recommend obtaining screening CBCs (OR, 0.40; 95% CI,
0.18-0.86; P = .01). In addition, when PCPs were asked about whether they recommended 1
screening vs repeated or periodic screening, more than 40% recommended repeated or periodic
screening for anemia in 65-year-old patients (132 of 324 [40.7%] for men and 133 of 324 [41.0%] for
women) (Figure 1).
Because several guidelines recommend screening for anemia during pregnancy, an additional
scenario of a 35-year-old pregnant woman was included to compare with the scenario of the
35-year-old woman who was not pregnant. For the pregnancy scenario, 105 of 325 PCPs (32.3%)
reported they did not provide care to pregnant patients within their practices, deferring care of
pregnant patients to obstetrics and gynecology specialists. Of the 220 PCPs who reported they
would see pregnant patients in their practice, 188 (85.5%) reported they would screen a pregnant
patient for anemia during her first trimester, as recommended in guidelines from the Centers for

Figure 1. Rates of Obtaining Complete Blood Counts (CBCs) for Detection of Anemia in Asymptomatic Patients
by Age, Sex, and Pregnancy Status for Healthy Patients Establishing Care With a Primary Care Physician

100

0 CBC

80 1 CBC
>1 CBC
Respondents, %

60

40

Data are based on survey responses of 325 primary


20 care physicians reporting recommendations of 1 CBC,
repeated CBCs, or no CBC. For pregnant women, there
were 220 respondents because primary care
0
Man Woman Man Woman Pregnant woman
physicians who did not provide care to pregnant
aged 35 y aged 35 y aged 65 y aged 65 y aged 35 y women were excluded.

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JAMA Network Open | Health Policy Diagnostic Testing and Evaluation of Iron Deficiency Anemia by US PCPs

Disease Control and Prevention and the American College of Obstetricians and Gynecologists but not
in the 2015 US Preventive Services Task Force updated guidelines.15-17

Interpretation of Laboratory Studies


To assess PCPs’ choices for additional laboratory tests to be performed for evaluation of IDA,
respondents were presented with a hypothetical scenario of a 65-year-old man reporting generalized
fatigue who had a hemoglobin level of 10.4 g/dL (to convert to g/L, multiply by 10.0) and mean
corpuscular volume of 72.3 fL (to convert to μm3, divide by 1.0). Measurement of ferritin level, the
most specific marker of iron deficiency, was the most common laboratory test recommended by
respondents (302 of 325 [92.9%]), followed by total iron-binding capacity and transferrin saturation
(278 of 325 [85.5%]).
To assess PCPs’ interpretation of iron laboratory studies, respondents were presented with a
series of laboratory values and asked to determine whether the anemia resulted from iron deficiency
or an alternate cause. For scenarios in which ferritin level and transferrin saturation were
concordantly low or normal, respondents correctly identified the cause with more than 93%
accuracy: 321 of 325 respondents (98.8%) correctly attributed anemia to iron deficiency in the
presence of a low transferrin saturation (6%) and a low ferritin level (11 ng/mL), and 303 of 325
(93.2%) correctly attributed anemia to an alternate cause in the presence of a normal transferrin
saturation (30%) and a normal ferritin level (150 ng/mL) (Figure 2). However, in scenarios of
discordant ferritin and transferrin saturation values, diagnostic accuracy decreased. For example, in
a scenario with a normal transferrin saturation (25%) but low ferritin level (6 ng/mL), 44 of 325
respondents (13.5%) misidentified the cause as something other than iron deficiency even though
the likelihood ratio for iron deficiency with a ferritin level less than 15 ng/mL is 51.9.18 In a scenario
with a low transferrin saturation (2%) but borderline low ferritin level (40 ng/mL), 86 of 325
respondents (26.5%) did not consider IDA as the cause even though the likelihood ratio for iron
deficiency with a transferrin saturation less than 5% is 10.5.18 In that scenario, 239 of 325
respondents (73.5%) correctly identified the scenario as IDA. There were no statistically significant
differences in correct interpretation of these scenarios by academic affiliation status, gender, stage in
clinical practice, or practice of ordering ferritin level measurement for anemia evaluation.

Diagnostic Evaluation of IDA


Of 325 respondents, 316 (97.2%) reported that PCPs, not specialists, were primarily responsible for
management of IDA within their practice settings. Respondents were asked about which tests they
would obtain in a series of scenarios with new-onset IDA and negative celiac serologic test results in

Figure 2. Interpretation of Iron Studies for Diagnosis of Iron Deficiency Anemia in 4 Scenarios With Different
Combinations of Ferritin Levels and Transferrin Saturation (TSAT)

100

Correct diagnosis
Incorrect diagnosis
80
Respondents, %

60

40

20

0
Low TSAT and Normal TSAT and Normal TSAT and Low TSAT and normal
Details of the scenarios are given in the Questionnaire
low ferritin level normal ferritin level low ferritin level to low ferritin level Design subsection of the Methods section.

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JAMA Network Open | Health Policy Diagnostic Testing and Evaluation of Iron Deficiency Anemia by US PCPs

men and women aged 35 or 65 years. For the 65-year-old patients, nearly all respondents
recommended initial GI endoscopic evaluation with colonoscopy and/or EGD (318 [97.9%] for
women and 314 [96.6%] for men). Most respondents recommended performing both EGD and
colonoscopy for 65-year-old patients (170 of 312 [54.5%] for women and 168 of 305 [55.1%] for men)
(Figure 3). However, some recommended colonoscopy alone (without EGD) for initial evaluation
(135 of 312 [43.3%] for women and 124 of 305 [40.7%] for men), which could lead to a potential
diagnostic delay and additional sedation episode if upper GI pathologic findings were present or
colonoscopy findings were normal. There were no statistically significant differences in the decision
to perform EGD and colonoscopy for 65-year-old patients based on respondents’ academic affiliation
status, gender, stage in clinical practice, practice type, or availability of open or direct access EGD and
colonoscopy (without prior GI consultation).
Although respondents reported managing IDA in 65-year-old men and women similarly, they
used a less invasive approach with 35-year-old patients. Of 325 PCPs, 314 (96.6%) recommended
initial endoscopy for a 65-year-old man, but only 250 of 323 (77.4%) recommended initial endoscopic
evaluation for a 35-year-old man (Figure 3). In addition, respondents reported differences in the use
of GI endoscopy for 35-year-old patients based on the patient’s sex. For example, a 35-year-old man
was more likely to undergo initial endoscopic evaluation with an EGD and colonoscopy than was a
35-year-old woman (OR, 5.68; 95% CI, 1.89-17.03; P = .001). However, even for a 35-year-old-man,
there was a potential for a diagnostic delay, with 73 of 323 respondents (22.6%) recommending
against initial endoscopic assessment. There were no statistically significant differences in
recommendations for diagnostic endoscopy for a 35-year-old man based on respondents’ academic
affiliation status, gender, stage in clinical practice, or practice type. The respondents were least likely
to recommend any initial endoscopic evaluation for a 35-year-old woman (45 of 314 [14.3%]). For a
35-year-old woman, using empirical iron supplementation first was recommended by 264 of 312
respondents (84.6%). Respondents’ academic affiliation status, gender, stage in clinical practice, and
practice type were not significantly associated with a decision to pursue diagnostic endoscopy for a 35-
year-old woman.

Discussion
In this nationally representative survey study of internal medicine PCPs, we found substantial
variation in the management of anemia. Specifically, we found self-reported evidence of both
overuse of screening CBCs (76.9% of respondents) and underuse of bidirectional endoscopy in
patients with IDA. Certain knowledge gaps also existed in the interpretation of discordant laboratory

Figure 3. Initial Diagnostic Evaluation Recommended by Respondents for Patients With New-Onset Iron
Deficiency Anemia and Negative Celiac Serologic Test Results by Age and Sex

100

EGD and colonoscopy


Colonoscopy only
80
EGD only
No endoscopy
Respondents, %

60

40

20

0
Man aged 65 y Woman aged 65 y Man aged 35 y Woman aged 35 y EGD indicates esophagogastroduodenoscopy.

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JAMA Network Open | Health Policy Diagnostic Testing and Evaluation of Iron Deficiency Anemia by US PCPs

test results, which may contribute to diagnostic errors. Specifically, 26.5% of respondents
misdiagnosed a scenario of IDA as anemia with an alternate cause despite a low transferrin saturation
(2%) and a borderline low ferritin level (40 ng/mL). Several subtle but important nuances in
interpretation of these studies may contribute to errors, including the high specificity of a low ferritin
level (98% specific for iron deficiency with a ferritin level ⱕ12 ng/mL),24 the potential for the ferritin
level to be normal or elevated in inflammatory states when a patient is iron deficient,2,18 and the
importance of measuring serum iron level in a fasting state to avoid potential confounders of dietary
or supplemental iron.25,26 Given the relatively high baseline prevalence of anemia of 5.6% in the US,13
incorrect interpretation of these laboratory results may lead to a substantial number of missed or
delayed diagnoses of IDA and, by extension, potential delays in diagnosis of GI tract malignant
neoplasm.
Our findings are in line with those of older studies on this topic. Prior work has found limited
clinical benefit associated with the common practice of obtaining routine CBCs for hospitalized
patients27,28 and outpatients.29-31 But in a repeated survey study of family medicine PCPs, the
frequency of routine CBCs remained persistently high between 1978 and 2004, with 67% of
respondents reporting that they would obtain a CBC for a 55-year-old woman in the most recent
survey.32 Although overuse is a complex phenomenon, these data suggest that routine laboratory
assessments are ingrained within medical practice. In this context, it is notable that, to our
knowledge, there are no guidelines (eg, from Choosing Wisely or other organizations) explicitly
recommending against screening for anemia in outpatients.17,33,34 In contrast, Choosing Wisely
explicitly recommends against routine or repeated CBCs for hospitalized patients.33,35 Although the
2015 US Preventive Services Task Force guidelines determined that there was insufficient evidence
to judge the benefits or harms of screening for anemia during pregnancy,17,34 there is a potential for
adverse neurodevelopmental outcomes during pregnancy when the woman has iron deficiency36;
multiple international guidelines have recommended screening for anemia during pregnancy despite
limited evidence.37 In this context of absent or conflicting recommendations, most respondents in
the present survey study nonetheless reported they would obtain screening CBCs for patients who
were pregnant or not pregnant. Prior work38,39 has also reported underuse of bidirectional
endoscopy, although not to the extent found in our study. Although previous guidelines
recommended bidirectional endoscopy for men and postmenopausal women,11 subsequent
American Gastroenterological Association guidelines, published after this survey was conducted,
recommend bidirectional endoscopy regardless of menopausal status for those without an alternate
explanation for IDA.12 Despite these recommendations, some physicians’ selection of colonoscopy
instead of combined EGD and colonoscopy for initial evaluation of IDA may be reflective of lack of
access. For example, in some practice settings, insurance reimbursements may disincentivize
combined EGD and colonoscopy, and physicians may not offer the combined procedures in a single
appointment.38,39 However, a serial diagnostic testing approach may lead to increased costs and
require that patients undergo a second episode of sedation. In addition, if there is a substantial time
interval between the colonoscopy and the EGD, there is the theoretical potential for a delay in
diagnosis (although serial testing was not directly assessed in this survey study).
Given the potential consequences of missed or underevaluated IDA and the complexities of test
interpretation, clinicians may benefit from tools within the electronic health record to help improve
diagnosis and reduce medical errors. For example, instead of displaying individual laboratory values
in isolation, a computer-assisted diagnostic tool could be developed to display an individualized
interpretation of the most likely cause of anemia in a patient. This would allow for more precise
interpretation of laboratory studies for individuals, such as interpreting iron studies for a patient with
inflammation. In addition, automated “trigger tools,” or detection algorithms for abnormal laboratory
patterns, may help identify cases of new-onset anemia that had been potentially missed by busy
clinicians.5 After abnormalities are identified by these tools, a common set of clinical actions could be
presented (eg, for ordering endoscopic testing) to help facilitate obtainment of appropriate tests and
minimize additional tasks for clinicians. Reducing unnecessary CBC ordering through education or

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JAMA Network Open | Health Policy Diagnostic Testing and Evaluation of Iron Deficiency Anemia by US PCPs

displaying cost of the laboratory testing alone is unlikely to be sufficient,40 but a multilevel
intervention incorporating education, price information, feedback, and financial incentives has
demonstrated success in an inpatient setting.41

Limitations
This study has limitations. Respondents may have answered questions based on what they believed
was the correct evidence-based practice rather than what was reflective of their actual clinical
practice, potentially introducing response bias. Other limitations include the possibility that
participants in the ACP Insiders Panel were more engaged with the organization and thus more aware
of current evidence-based practices. Both of these biases would suggest that the knowledge gaps
identified in our study are underestimates of those seen in actual practice. The results may not apply
to other professionals who provide primary care, such as family medicine physicians or advanced
practice physicians. A potential for nonresponse bias exists, and those who did not respond may
have been less knowledgeable about the topic or may have differed in other ways related to the
outcomes of interest. However, we attempted to mitigate this bias through systematic efforts to
increase responses. In addition, we analyzed available demographic data for respondents and
nonrespondents and found no significant differences in age, geographic location, or career stage;
however, respondents were more likely to be White and male than were nonrespondents. Survey
methods may not be as well suited for the study of actual practice behaviors as other methods.
However, our survey allowed us to indirectly assess physician knowledge and behavior with uniform,
ideal clinical scenarios, which is not possible when secondary data are used.

Conclusions
In this survey study, PCPs’ self-reported testing practices for anemia suggest overuse of screening
laboratory tests, misinterpretation of iron studies, and underuse of bidirectional endoscopy in
evaluation of new-onset IDA. These findings suggest that IDA, a common clinical condition and early
sign of GI malignant neoplasm, is not uniformly understood, approached, and managed by practicing
physicians in the US. Given the potential association with GI cancers and the increasing incidence of
colorectal cancer in younger adults, thorough evaluation of IDA is important for preventing delays in
diagnosis.3,4,9 Further work should inform the design and implementation of tools to improve
diagnostic evaluation of IDA and reduce the risk of potential diagnostic errors.

ARTICLE INFORMATION
Accepted for Publication: August 1, 2021.
Published: October 1, 2021. doi:10.1001/jamanetworkopen.2021.27827
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Read AJ
et al. JAMA Network Open.
Corresponding Author: Andrew J. Read, MD, MS, Division of Gastroenterology and Hepatology, Department of
Internal Medicine, University of Michigan, Ann Arbor, 3912 E Taubman Center, 1500 E Medical Center Dr, SPC 5362,
Ann Arbor, MI 48109-5362 (reada@med.umich.edu).
Author Affiliations: Department of Internal Medicine, University of Michigan, Ann Arbor (Read, Waljee, Sussman,
Chen, Vijan, Saini); Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor (Read, Waljee,
Sussman, Vijan, Saini); Veterans Affairs Health Services Research and Development, Center for Clinical
Management Research, Ann Arbor, Michigan (Waljee, Sussman, Vijan, Saini); Center for Innovations in Quality,
Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine,
Houston, Texas (Singh).
Author Contributions: Dr Read had full access to all of the data in the study and takes responsibility for the
integrity of the data and the accuracy of the data analysis.
Concept and design: Read, Waljee, Sussman, Saini.

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JAMA Network Open | Health Policy Diagnostic Testing and Evaluation of Iron Deficiency Anemia by US PCPs

Acquisition, analysis, or interpretation of data: Read, Sussman, Singh, Chen, Vijan, Saini.
Drafting of the manuscript: Read, Waljee.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Read, Waljee, Vijan.
Obtained funding: Read, Saini.
Administrative, technical, or material support: Read, Sussman.
Supervision: Sussman, Chen, Vijan, Saini.
Conflict of Interest Disclosures: Dr Saini reported receiving research and employment support from the
Department of Veterans Affairs. No other disclosures were reported.
Funding/Support: This work was supported by grant NIH KL2TR002241 from the National Institutes of Health (Dr
Read) and grant CIN13-413 from the Veterans Affairs Health Services Research and Development Service Center
for Innovations in Quality, Effectiveness and Safety (Dr Singh).
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection,
management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and
decision to submit the manuscript for publication.
Additional Contributions: The American College of Physicians Internal Medicine Insiders Panel staff helped with
survey distribution and analysis of survey panel demographics. Brian Zikmund-Fisher, PhD, and the University of
Michigan Center for Bioethics and Social Sciences in Medicine Working Group provided feedback in survey
development. Contributors were not compensated for their work.

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SUPPLEMENT.
eAppendix. Anemia Survey

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