Health Policy 125 (2021) 191–202

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Health Policy
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Impact of interprofessional collaboration on chronic disease

management: Findings from a systematic review of clinical trial and
meta-analysis
Domenico Pascucci a , Michele Sassano a , Mario Cesare Nurchis b,∗ , Michela Cicconi a,b ,
Anna Acampora a,c , Daejun Park d , Carmen Morano e,1 , Gianfranco Damiani a,b,1
a
Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168, Rome, Italy
b
Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168, Rome, Italy
c
Dipartimento di Epidemiologia del Servizio Sanitario Regionale-Regione Lazio, ASL Roma 1, Via Cristoforo Colombo 112, 00147, Rome, Italy
d
Department of Social Work, Ohio University, Athens, OH, 45701, USA
e
University at Albany, State University of New York, 135 Western Ave RI 221, Albany, NY, 12222, USA

a r t i c l e i n f o a b s t r a c t

Article history: Improvement of chronic disease management demands effective collaborative relationships between
Received 9 September 2020 health and social-care which is achieved through teamwork. Interprofessional Education (IPE) and Inter-
Received in revised form professional Collaboration (IPC) are recognized as essential for the delivery of effective and efficient
21 November 2020
healthcare. Although IPC and IPE are key components of primary care, evidence of studies evaluating
Accepted 11 December 2020
how an IPE intervention prior to IPC improved chronic patient outcomes remains scarce. The aim of this
study was to assess the impact of IPC interventions on the management of chronic patients compared to
Keywords:
usual care.
Interprofessional education
Interprofessional collaboration
A systematic review and meta-analysis of Randomized Controlled Trials (RCTs) on IPC interventions
Chronic diseases on chronicity management and their impact on clinical and process outcomes was conducted.
Chronic disease management Of the 11,128 papers initially retrieved, 23 met the inclusion criteria. Meta-analyses results showed
the reduction of systolic blood pressure (Mean Difference (MD) -3.70; 95 % CI -7.39, -0.01), glycosylated
hemoglobin (MD -0.20; 95 % CI -0.47, -0.07), LDL cholesterol (MD -5.74; 95 % CI -9.34, -2.14), diastolic
blood pressure (MD -1.95; 95 % CI -3.18, -0.72), days of hospitalization (MD -2.22; 95 % CI -4.30, -0.140).
A number of positive findings for outcomes related to IPC were found reflecting an improvement of
quality of care and an enhancement in the delivery of patient-centered and coordinated care. Moreover,
the need for a purposeful systemic approach linking interprofessional education with interprofessional
collaboration and patient health and wellbeing is necessary.
© 2020 Elsevier B.V. All rights reserved.

1. Background
The world is rapidly ageing and, indeed, from 2015 to 2050 the
population aged 60 years and older is foreseen to be 2 billion: this
growth is fueled by the post WWII ‘Baby Boom’ and the fact that
people worldwide are living longer [1].
However, as people age, their health needs tend to become more
complex with a general trend towards declining capacity and the
increased likelihood of having one or more chronic diseases [2].
According to the Noncommunicable diseases (NCDs) Country Pro-
files 2018, authored by the WHO, “NCDs are the leading cause of
∗ Corresponding author.
E-mail address: nurchismario@gmail.com (M.C. Nurchis).
1
Gianfranco Damiani and Carmen Morano are co-senior Authors.
death globally, and one of the major health challenges of the 21 st
century. NCDs are by far the leading cause of death worldwide. In
2016, they were responsible for 71 % (41 million) of the 57 million
deaths which occurred globally” [3].
The increasing prevalence of chronic disease, which is often
underestimated [4] creates significant financial, social and psycho-
logical burden for patients, families and the healthcare system [5].
A recent study indicates that the total economic cost of chronic
conditions in the USA in 2015–2050 is USD 94.9 trillion [6].
Improvement of chronic disease management demands effec-
tive collaborative relationships between health and social-care
which are best achieved through teamwork [7]. This supported
with a growing evidence, much of it from the USA, suggesting that
team-based interventions in chronic disease are associated with
better patient outcomes, and the involvement of nurses in assess-
ment, treatment, self-management support and follow up has been

https://doi.org/10.1016/j.healthpol.2020.12.006
0168-8510/© 2020 Elsevier B.V. All rights reserved.
D. Pascucci et al.
linked to improved professional adherence to guidelines, patient
satisfaction, clinical health status, and use of health services [8].
Interprofessional Education (IPE) is the primary mechanism for
preparing health care professionals to engage in Interprofessional
Collaboration (IPC). Consequently, it should not be surprising that
IPE as well as IPC in health-care has significantly increased in the
past two decades.
IPE as described by Reeves and colleagues occurs “when mem-
bers of more than one health or social care (or both) profession
learn interactively together, for the explicit purpose of improving
interprofessional collaboration or the health/well-being (or both)
of patients/clients. Interactive learning requires active learner par-
ticipation, and active exchange between learners from different
professions”. The widespread advocacy and implementation of IPE
reflects the premise that IPE will contribute to developing health-
care providers with the skills and knowledge needed to work in a
collaborative way [9].
There is a growing body of evidence about the impact of IPE on
changing learner outcomes [10], health professionals’ ethics [11],
teamwork [12] among other processes of IPC.
Interprofessional collaboration (IPC) is defined as a work-
sharing cooperation in which professionals from more than one
health or social care profession cooperate with the explicit goal
of improving collaboration and/or increasing patient-related care
quality [13].
From an operative point of view, IPC is characterized by a variety
of interventions occurring most often within healthcare settings
and it includes, for instance, interprofessional checklists, meetings,
communication tools, briefings, forms, and pathways [9,13].
It is also important to highlight that, in the scientific literature,
there is conceptual confusion about the varied terms which may be
due to the large number of articles written by experienced practi-
tioners rather than pure academics.
The peculiarity of IPC lies in the interactive effort and the support
of professionals which are essential to reach the outcome and this
foresees a high level of communication, mutual planning, collective
decisions and shared responsibilities [13].
For this reason, one must take care when evaluating such stud-
ies, to ensure one understands the nature and key activities of the
intervention, whatever it may be named.
Nowadays, IPC is essential for the proper delivery of health-care
services given the complex composition of patients’ needs and the
wide range of health-care providers and organizations [14–16].
Although the scientific literature continues to advocate IPC and
IPE as key components of primary care [17], there is a paucity of
evidence linking IPE and IPC with improved patient outcomes [18].
As the number of adults living with chronic disease across the globe
continues to grow at an unprecedented rate and policy encourages
and/or mandates IPC, evidence of the effectiveness of IPC following
an IPE intervention is needed.
Furthermore, evidence of studies evaluating how an IPE inter-
vention prior to IPC improved chronic patient outcomes remains
scarce.
Consequently, this review was forced to narrow its attention
on the role of the IPC. Thus, the aim of this systematic review was
to assess the impact of IPC interventions on the management of
chronic patients compared to standard health-care practice.
2. Materials and methods
2.1. Study design and literature search
A systematic review of the literature was carried out querying
the following electronic databases: EMBASE, ISI Web of Knowledge,
MEDLINE, from their inception to April 2020, without language
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Health Policy 125 (2021) 191–202
restrictions. The Population, Intervention, Comparator, Outcome
(PICO) model was used to frame the following guiding question
of the systematic review: What is the impact of IPC intervention on
chronicity management? Each PICO domain corresponded to the
following elements: (P) Chronic condition, (I) IPC, (C) usual care
and (O) impact on clinical outcomes, process outcomes and patients
reported outcomes (PROs) [19].
To ensure the systematic review quality, the Preferred Reporting
Items for Systematic Reviews, and Meta-Analyses (PRISMA) check-
list and flow-diagram was used [20].
Taking into account the search strategy conducted by Reeves
et al. [13], the search string was constructed combining keywords
such as “chronic disease”, “chronic condition”, “chronic illness”,
“interprofessional collaboration”, “interprofessional team”, “Out-
come and Process Assessment”, “effect” and their synonymous
through Boolean operators “AND” and “OR”.
Psychiatric disorders, palliative care and chronic functional pain
were excluded from the string with the Boolean operator NOT.
Finally, additional studies were identified by the “hand search”
of references from articles included in the review (i.e. snowball
searching).
2.2. Study selection
The screening of titles and abstracts of all records was conducted
to identify potentially relevant publications. The inclusion criteria
for this review were: clinical trials published in English or Italian
that quantitatively assessed outcomes and processes of IPC inter-
vention on the management of chronic patients compared to usual
care and the presence of at least one physician in the team.
Usual care was defined as the care the targeted patient popu-
lation would be expected to receive as part of the normal practice
without explicitly stressing any degree of collaboration [21].
Indeed, including studies with a usual care model already based
on a collaborative form, could lead to the risk of influencing
expected results between the two models and an underestimation
of the effects on the health outcomes.
Thus, only studies where usual care was defined according to
what stated above were included.
Articles were excluded if they did not meet the inclusion criteria
or if they met at least one of the following exclusion criteria: study
design other than clinical trial and articles that included students
in the teams.
The evaluation of the eligibility criteria was performed inde-
pendently by the two authors and, in case of divergence, a third
researcher was consulted.
2.3. Quality assessment
Two investigators assessed independently the quality of the
studies using the National Institute of Health’s Quality Assessment
of Controlled Intervention Studies [22].
If disagreements occurred, the final decision was reached by
team consensus. The tool assesses 14 parameters for evaluating
the internal validity of a study. For each item, the investigator could
select “yes,” “no,” or “cannot determine/not reported/not applica-
ble” [22]. A potential risk of bias was considered if the item was
rated as “no” or “cannot determine/not reported/not applicable”
were selected for the items by the reviewer. If the “yes” answers
were ≥75 % of the total, an article was considered of “good” quality;
if they were <75 % but ≥ 50 %, an article was scored as “fair”; if they
were < 50 %, the article was scored as “poor” [23].
D. Pascucci et al.
2.4. Data extraction and data analysis
Two reviewers performed data extraction and a standardized
form was used to tabulate the following data: bibliographic details,
country, intervention team, setting, intervention, comparator, pop-
ulation, indicators, main results.
The pooled mean difference (MD) and 95 % confidence interval
(CI) were estimated in order to summarize continuous data [24].
A random effects meta-analysis was carried out to account for
between-study variance [25]. The I2 statistics, which describes the
percentage of variability in estimates across studies due to hetero-
geneity rather than sample error (i.e. chance) [26], was adopted
to assess heterogeneity. Studies were checked for data duplica-
tion, and if two or more articles used totally or partially the same
population only the one using the larger number of study partic-
ipants was included in quantitative or semi-quantitative analysis.
If a study reported only stratified results for an indicator, all strata
were included in data synthesis.
A leave-one-out sensitivity analysis was performed by itera-
tively removing one study at a time to confirm that our findings
were not strongly influenced by any single study. Furthermore, the
analysis was repeated excluding studies reporting m̈ean change
from baseline¨.
Given the highly diverse nature of the studies analyzed, several
stratified meta-analyses were carried out to explore the efficacy
of the intervention. However, subgroup analysis was performed
only if more than three studies reporting results about the same
indicator were available. In particular, through stratification, the
influence of the following factors was analyzed: patient condi-
tion (Cardiovascular Diseases-CVD, Diabetes Mellitus type II-DM
II, Chronic Kidney Disease-CKD); study sample size (<250; ≥250);
duration of the follow-up (<12 months; ≥12 months); presence of
pharmacist in the team (no; yes); drop-out rate at endpoint 20 %
or lower (no; yes); participants and providers blinded (no; yes);
patient education about their condition as a part of the interven-
tion (no; yes); motivational support as a part of the intervention
(no; yes).
All meta-analyses were performed using statistical software
STATA (version 13.0; College Station, TX, USA) and two-sided P
values <0.05 were considered statistically significant.
Given the infeasibility of a meta-analysis approach, for indica-
tors lacking uniformity and homogeneity among the studies (e.g.
very different definitions or different indicators for the same out-
come), results were synthesized semi-quantitatively to assess the
strength of the evidence according to three levels of scientific evi-
dence similarly to those developed by Hogendoorn and colleagues
(2000) [27]:
• Strong evidence: provided by generally consistent findings in
multiple good-quality studies;
• Moderate evidence: provided by generally consistent findings in
one good-quality study and one or more fair-quality studies, or
in multiple fair-quality studies;
• Insufficient evidence: only one study available or inconsistent
findings in multiple studies.
The findings of the studies were considered to be inconsistent
if less than 75 % of the available studies reported the same con-
clusion. In the case of multiple good-quality studies, the available
fair-quality studies were disregarded in the assessment of the level
of evidence.
Only studies that met the eligibility criteria and that were clas-
sified as fair or good quality were included in this rating system.
Results of studies reported in multiple articles were included only
once in each evaluation. Only the items reported in at least two
articles have been considered.
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Health Policy 125 (2021) 191–202
The effect of IPC was evaluated, according to the semi-
quantitative assessment, by collecting the items that were analyzed
by the articles categorizing them into three main groups: (1)
Clinical outcomes, (2) Clinical process measures and (3) Patient
Reported Outcomes (PROs).
3. Results
3.1. Study selection
The literature search resulted in 11,128 studies and 10 studies
were retrieved through snowball search method. After elimi-
nating duplicates, the research team reviewed a total of 8149
manuscript titles and abstracts. A total of 55 full articles were
considered potentially relevant and reviewed by two independent
researchers. After full text examination, 32 of 55 articles were
excluded as they did not fulfill selection criteria. The remaining
23 [28–50] studies were included in the systematic review. Out of
23, 13 [28,29,32,33,35,37,40–44,46,50] studies were considered for
the meta-analysis while 18 [28–31,33,36–40,42,44,45,29–50] were
considered for the semiquantitative analysis (Fig. 1).
3.2. Characteristics of the studies
The included studies were published between 1995 and 2017,
of which 13 in the USA [28–30,32,36,40–44,47,49,50] and 3 in
the Netherlands [31,37,38]. Overall, 8772 patients were enrolled
in the 23 studies (range: 80–2199), 14 [30–33,35,36,39,40,42–47]
of which enrolled fewer than 250 patients. The majority of
the studies assessed the impact of IPC among patients affected
by cardiovascular diseases [28,30,31,38,39,41,45,47,48], multi-
chronic conditions [32,34–36,42,43,46,50], chronic kidney disease
[29,37,49]. Only 2 papers considered diabetes mellitus type II
[40,44] and one chronic obstructive pulmonary disease [33],
respectively. Nurse [28,30–33,35–43,45–49] was the most rep-
resented professional in the intervention team followed by
primary care physician [29,30,32,35,36,40,42,44–50] and pharma-
cist [29,34,40,41,44,46,49,50]. The most frequent setting of the
studies was outpatient clinic [29–31,33,37–39,41,48,49] while the
hospital setting [28,45] and the pharmacy [34,50] were consid-
ered in only 2 studies, respectively. Intensive education about
own condition and motivation or psychosocial support were
reported in 1 [28,29,31,31,32,33,38–40,44,47,46–49] and 5 articles
[32,37–39,43] respectively.
A summary of the characteristics of each study is reported in
Appendix Table 1.
3.3. Quality assessment
A score of ten or greater was indicative of good methodological
quality, nine to seven was fair and studies scoring below seven were
deemed to be of poor quality. The overall methodological quality
of all included studies (n = 23) is summarized in Appendix Table 2.
Fifteen studies [28–34,36,38,39,44,47–50] were deemed of good
quality, while 8 [35,37,40–43,45,46] were rated of fair quality
showing a moderate risk of bias.
The most frequently met quality criteria regarded randomiza-
tion criteria, power calculation and the use of intention-to-treat
analysis. A number of items were rarely reported, including those
regarding adherence to treatment or avoiding other intervention.
The drop-out rate at endpoint was 20 % or lower in 19 studies
[28–34,36,38,40–45,47–50].
D. Pascucci et al.
Fig. 1. PRISMA flow diagram of different screening rounds.
3.4. Clinical outcomes
3.4.1. Systolic blood pressure
Eight studies [29,32,37,40,41,43,46,50] evaluated the effect of
the intervention on systolic blood pressure (SBP) on a total of 4704
patients. SBP was significantly lower in the intervention group in
5 studies [32,37,40,41,50]. In these articles the professionals most
represented in the intervention teams were nurses [32,37,40] and
pharmacists [40,50]. The interventions were delivered at outpa-
tient clinics [37,41], pharmacy [50], Veterans Affairs (VA) medical
center [40] or in primary care clinics [32]. In some cases, the inter-
vention was characterized by education work on patient [32,40]
and motivational support [32,37].
A meta-analysis to assess the difference of SBP levels
between IPC and usual care was performed including 8 studies
[29,32,37,40,41,43,46,50].
An overall statistically significant mean difference was found in
favor of the IPC (MD -3.70; 95 % CI -7.39, -0.01), with a significant
high heterogeneity among studies (I2 = 92.2 %, p < 0.001) (Fig. 2).
However, when stratifying for the disease of the patients, no
statistically significant effect of the intervention of SBP was shown.
Instead, a statistically significant effect of the intervention was
found by including in the analysis only studies with a follow up
< 12 months (MD -9.601; 95 % CI -11.106, -8.097). The absence
of blindness and of an educational intervention, also significantly
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Health Policy 125 (2021) 191–202
influenced the results. The remaining stratifications failed to show
significant differences between intervention and control (Table 1).
The results obtained after excluding studies reporting “mean
change from baseline” are reported in the Appendix 1 Table 3.
3.4.2. Glycated hemoglobin
The effect of ICP on blood levels of Glycated Hemoglobin
(HbA1c) was reported by 8 studies [32,37,40,42–44,46,50]. Over-
all, these studies included 1860 patients. Out of 8 studies, 5 articles
[32,40,42,44,50] found that HbA1c levels were significantly lower
in the intervention groups. The intervention teams in these stud-
ies were characterized especially by the presence of pharmacists
[40,44,46,50] and nurses [32,40,42] in the intervention team. The
majority of teams worked in a primary care center [32,42,44], while
the rest in a pharmacy [50] and in VA medical center [40]. The
patients were educated about their illness in 3 studies [32,40,44]
and received motivation support in 2 studies [32,37].
A meta-analysis on HbA1c was carried out including 8 studies
[32,37,40,42–44,46,50].
The pooled MD was -0.20 (95 % CI -0.47, -0.07) in favor of
the intervention, with a statistically significant high heterogeneity
between studies (I2 = 90.8 %, p < 0.001) (Fig. 2).
The stratified analyses identified as a possible influencing factor
the sample size ≥ 250 (MD -0.920; 95 % CI -1.120, -0.720), even if
only one study considered this condition. The remaining stratifi-
D. Pascucci et al. Health Policy 125 (2021) 191–202

Fig. 2. Comparison of the effect of IPC and usual care on the reduction of Systolic Blood Pressure, Glycated Hemoglobin, LDL cholesterol, and Diastolic Blood Pressure.

Table 1
Meta-analysis of the reduction of blood pressure levels stratified by patient condition; study sample size; duration of the follow-up; presence of pharmacist in the team;
drop-out rate at endpoint 20 % or lower; participants and providers blinded; patient education about their condition as a part of the intervention ; motivational support as a
part of the intervention.

Systolic Blood Pressure

Subgroup RCTs N Intervention group, N Control group, N MD (95 % CI) p I2 , %

Diseases
CVD 5 861 859 −4.342 (-8.724, 0.041) 0.052 85.3%
DM II 5 719 698 −3.594 (-8.339, 1.152) 0.138 83.4%
CKD 3 1595 1613 −3.555 (-9.887, 2.777) 0.271 97.5%
Study size
<250 4 349 345 −1.581 (-4.540, 1.378) 0.295 20.4%
≥250 4 1787 1823 −5.291 (-10.937, 0.355) 0.066 96.9%
Follow-up
<12 months 3 612 612 −9.601 (-11.106, -8.097) <0.001 0.0%
≥12 months 5 1524 1556 −0.334 (-1.616, 0.948) 0.610 9.9%
Presence of pharmacist
no 3 367 347 −1.515 (-3.315, 0.286) 0.099 0.0%
yes 5 1769 1821 −5.683 (-11.555, 0.189) 0.058 95.8%
Drop-out rate at endpoint 20 % or lower
no 2 242 211 −1.826 (-3.782, 0.129) 0.067 0.0%
yes 6 1894 1957 −4.367 (-9.287, 0.553) 0.082 94.0%
Participants and providers blinded
absent or undefined 6 979 959 −4.898 (-8.802, -0.995) 0.014 87.6%
clearly stated 2 1157 1209 0.564 (-0.837, 1.966) 0.430 0.0%
Patient education about their condition
no 5 910 882 −4.390 (-8.664, -0.115) 0.044 0.0%
yes 3 1126 1286 −1.714 (-5.941, 2.514) 0.427 65.7%
Motivational support
no 5 1769 1821 −5.683 (-11.555, 0.189) 0.058 95.8%
yes 3 367 347 −1.515 (-3.315, 0.286) 0.099 0.0%

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Table 2
Meta-analysis of the reduction of glycosylated hemoglobin levels stratified by patient condition; study sample size; duration of the follow-up; presence of pharmacist in
the team; drop-out rate at endpoint 20 % or lower; participants and providers blinded; patient education about their condition as a part of the intervention ; motivational
support as a part of the intervention.

Glycosylated hemoglobin

Subgroup RCTs N Intervention group, N Control group, N MD (95 % CI) p I2 , %

Diseases
CVD 5 697 713 −0.332 (-0.752, 0.088) 0.122 93.6%
DM II 7 788 801 −0.204 (-0.576, 0.168) 0.283 91.8%
CKD 2 490 494 −0.457 (-1.359, 0.444) 0.320 98.2%
Study size
<250 7 538 499 −0.085 (-0.248, 0.078) 0.307 61.0%
≥250 1 370 353 −0.920 (-1.120, -0.720) <0.001
Follow-up
<12 months 2 567 545 −0.609 (-1.299, 0.082) 0.084 83.5%
≥12 months 6 341 337 −0.076 (-0.251, 0.099) 0.395 65.8%
Presence of pharmacist
no 4 411 405 −0.170 (-0.450, 0.110) 0.235 64.8%
yes 4 497 507 −0.125 (-0.752, 0.503) 0.697 96.0%
Drop-out rate at endpoint 20 % or lower
no 2 156 147 −0.035 (-0.086, 0.017) 0.184 0.0%
yes 6 752 765 −0.224 (-0.659, 0.211) 0.313 85.5%
Participants and providers blinded
absent or undefined 7 872 876 −0.194 (-0.582, 0.195) 0.328 90.1%
clearly stated 1 36 36 −0.040 (-0.095, 0.015) 0.154
Patient education about their condition
no 5 711 716 −0.248 (-0.563, 0.066) 0.122 93.6%
yes 3 197 196 0.036 (-0.713, 0.786) 0.924 78.4%
Motivational support
no 5 576 585 −0.210 (-0.731, 0.311) 0.430 95.0%
yes 3 332 327 −0.086 (-0.372, 0.199) 0.554 56.5%

cations failed to show significant differences between intervention
and control (Table 2).
The results obtained after excluding studies reporting “mean
change from baseline” are reported in the Appendix 1 Table 4.
3.4.3. LDL cholesterol
Five studies [32,37,40,41,50] examined the relationship
between IPC and blood levels of LDL cholesterol in a total sample
of 1514 patients. In two articles [32,50] the decrease in LDL levels
was statistically significant in the intervention group.
A meta-analysis evaluating LDL levels was carried out including
5 studies [32,37,40,43,50].
An overall statistically significant mean difference of LDL choles-
terol between intervention and usual care was found (MD -5.74; 95
% CI -9.34, -2.14; I2 = 29.5 %, p = 0.214) (Fig. 2).
In addition, stratified meta-analyses showed a statistically sig-
nificant effect if the interventions were delivered to patient with
CKD (MD -7.426; 95 % CI -10.365, -4.488), if follow up was ≥ 12
months (MD -5.459; 95 % CI -10.795, -0.122), if the pharmacist was
absent (MD -5.459; 95 % CI -10.795, -0.122), if there were no educa-
tional interventions (MD -6.487, 95 % CI -9.614, -3.359), and if there
was a motivational support (MD -5.459, 95 % CI -10.795, -0.122).
Furthermore, for the study sample size ≥ 250 and a drop-out
rate at endpoint of 20 % or lower, each characterizing one single
study, a statistically significant effect of the intervention was found
(Table 3).
The results obtained after excluding studies reporting “mean
change from baseline” are reported in the Appendix 1 Table 5.
3.4.4. Diastolic blood pressure
Of the 23 included studies, 4 [37,41,46,50] analyzed the Dias-
tolic Blood Pressure (DBP) in 1538 patients. The DBP levels were
significantly lower in the intervention group than in the control
group in 2 studies [37–50].
A meta-analysis assessing the effect of IPC on DBP levels was
carried out including 4 studies [37,41,46,50].
The MD showed a reduction in DBP of 1.95 (95 % CI -3.18, -0.72;
I2 = 48.3 %, p = 0.122) in favor of the intervention (Fig. 2).
Stratification by diseases did not influence the results that
remained significant in all subgroups. Statistically significant effect
was shown for the follow up < 12 months (MD -2.563; 95 % CI -
3.826, -1.301), for a drop-out rate 20 % or lower (MD -2.563; 95 %
CI -3.826, -1.301).
In addition, after exclusion of studies with a sample size <250,
the presence of a pharmacist and the absence of a clear blindness
of participants, results show a statistically significant difference
between intervention and control groups (Table 4).
The results obtained after excluding studies reporting “mean
change from baseline” are reported in the Appendix 1 Table 6.
3.4.5. Smoking cessation
Of the 23 included studies, a good quality one [50] and 3 fair
quality ones [37,40,42] have analyzed the impact of IPC on smoking
cessation. The former [50] described a significant reduction in the
intervention group in smoking habit and the achievement of the
recommended targets for all cardiovascular risk factors at 3 months
including pharmacists in the team. Nevertheless, the application
of the rating system has shown insufficient evidence because of
inconsistent findings in multiple studies (Table 5).
3.4.6. Mortality
The effect of interventions on mortality was analyzed by 6 good
[28,29,38,39,48,49] and 2 fair- quality studies [10–18]. Almost all
studies evaluated mortality from all causes except Hendrix et al [38]
who focused the attention on cardiovascular deaths among patients
with atrial fibrillation managed in an outpatient clinic. The study of
Stewart et al [48] expressed mortality as free event survival with-
out showing a significant correlation with the intervention. The
rating system assigned insufficient evidence because of inconsis-
tent findings in multiple good quality studies [28,29,38,39,48,49]
(Table 5).

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Table 3
Meta-analysis of the reduction of LDL cholesterol levels stratified by patient condition; study sample size; duration of the follow-up; presence of pharmacist in the team;
drop-out rate at endpoint 20 % or lower; participants and providers blinded; patient education about their condition as a part of the intervention ; motivational support as a
part of the intervention.

LDL cholesterol

Subgroup RCTs N Intervention group, N Control group, N MD (95 % CI) p I2 , %

Diseases
CVD 3 582 569 −5.782 (-11.640, 0.075) 0.053 39.1%
DM II 4 632 618 −4.488 (-10.090, 1.113) 0.116 42.0%
CKD 2 482 455 −7.426 (-10.365, -4.488) <0.001 0.0%
Study size
<250 4 374 367 −4.315 (-9.468, 0.837) 0.101 36.6%
≥250 1 370 353 −8.000 (-12.500, -3.500) <0.001
Follow-up
<12 months 2 567 545 −4.417 (-13.910, 5.076) 0.362 60.5%
≥12 months 3 177 175 −5.459 (-10.795, -0.122) 0.045 33.7%
Presence of pharmacist
no 3 324 318 −5.459 (-10.795, -0.122) 0.045 33.7%
yes 2 420 402 −4.417 (-13.910, 5.076) 0.362 60.5%
Drop-out rate at endpoint 20 % or lower
no 1 112 102 −7.000 (-10.880, -3.120) <0.001
yes 4 632 618 −4.488 (-10.090, 1.113) 0.116 42.0%
Participants and providers blinded
absent or undefined 5 744 720 −5.740 (-9.340, -2.140) 0.002 29.5 %
clearly stated 0 0 0
Patient education about their condition
no 3 588 563 −6.023 (-10.051, -1.994) 0.003 35.3%
yes 2 156 157 −4.123 (-15.488, 7.242) 0.477 55.3%
Motivational support
no 2 420 402 −4.417 (-13.910, 5.076) 0.362 60.5%
yes 3 324 318 −5.459 (-10.795, -0.122) 0.045 33.7%

Table 4
Meta-analysis of the reduction of diastolic blood pressure levels stratified by patient condition; study sample size; duration of the follow-up; presence of pharmacist in the
team; drop-out rate at endpoint 20 % or lower; participants and providers blinded; patient education about their condition as a part of the intervention ; motivational support
as a part of the intervention.

Diastolic Blood Pressure

Subgroup RCTs N Intervention group, N Control group, N MD (95 % CI) p I2 , %

Diseases
CVD 3 649 642 −2.669 (-3.766, -1.572) <0.001 0.0%
DM II 2 457 432 −2.964 (-4.182, -1.746) <0.001 0.0%
CKD 2 525 484 −1.924 (-3.804, -0.043) 0.045 80.1%
Study size
<250 1 87 79 −3.300 (-6.880, 0.280) 0.071
≥250 3 717 694 −1.807 (-3.189, -0.425) 0.010 60.8%
Follow-up
<12 months 2 562 563 −2.563 (-3.826, -1.301) <0.001 9.1%
≥12 months 2 242 210 −1.489 (-3.334, 0.356) 0.114 31.3%
Presence of pharmacist
no 1 155 131 −1.000 (-2.068, 0.068) 0.066
yes 3 649 642 −2.669 (-3.766, -1.572) <0.001 0.0%
Drop-out rate at endpoint 20 % or lower
no 2 242 210 −1.489 (-3.334, 0.356) 0.114 31.3%
yes 2 562 563 −2.563 (-3.826, -1.301) <0.001 9.1%
Participants and providers blinded
absent or undefined 3 717 694 −1.807 (-3.189, -0.425) 0.010 60.8%
clearly stated 1 87 79 −3.300 (-6.880, 0.280) 0.071
Patient education about their condition
no 4 804 773 −1.951 (-3.181, -0.722) 0.002 48.3 %
yes 0 0 0
Motivational support
no 3 649 642 −2.669 (-3.766, -1.572) <0.001 0.0%
yes 1 155 131 −1.000 (-2.068, 0.068) 0.066

3.4.7. Incidence of end-stage renal disease 3.5. Clinical process measures

The effect of IPC on the occurrence of End-Stage Renal Disease
(ESRD) was reported by 2 good-quality studies [29,49]. In both
studies there was no difference between the control and interven-
tion arm. However, the rating system rated insufficient evidence
because of inconsistent findings (Table 5).
3.5.1. Days of hospitalization
Three studies [28,33,35] reported data regarding the length of
hospitalization. Rich et al. [28] showed a net reduction in hospital
use (p = 0.04) due to heart failure. Likewise, Ko et al. [33] indicated a
shorter length of stay in hospital for COPD exacerbations (p < 0.001).

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D. Pascucci et al. Health Policy 125 (2021) 191–202

Table 5
Findings of the impact of Interprofessional Collaboration on clinical outcomes, clinical process measures, patient reported outcomes.

Category Reference Result Evidence

Clinical Outcomes
Smoking cessation INSUFFICIENT
Peeters 2013 n.s.
Cohen 2011 n.s.
Litaker 2003 +
Tsuyuki 2016 +
Mortality INSUFFICIENT
Rich 1995 n.s.
Cooney 2015 n.s.
Peeters 2013 n.s.
Hendrix 2012 +
Stromberg 2003 +
Blue 2001 n.s.
Stewart 2015 n.s.
Ishani 2016 n.s.
Incidence of ESRD INSUFFICIENT
Cooney 2015 n.s.
Ishani 2016 n.s.
Clinical Process Measures
Influenza vaccination coverage MODERATE
Litaker 2003 +
Hogg 2009 +
Diabetic foot examination MODERATE
Litaker 2003 +
Choe 2005 +
Retinal examination INSUFFICIENT
Litaker 2003 n.s.
Choe 2005 +
Hogg 2009 +
Medication adherence INSUFFICIENT
Cooney 2015 n.s.
Litaker 2003 +
Patient Reported Outcomes (PROs)
Specific Quality-of-Life In.s.truments STRONG
Rich 1995 +
Kasper 2002 +
Ko 2016 +
Generic Quality-of-Life Instruments INSUFFICIENT
Cooney 2015 n.s.
Lok 2007 +
Von Korff 2011 +
Litaker 2003 n.s.
Hogg 2009 n.s.
Dunagan 2005 n.s.

The good-quality studies are in bold. Levels of evidence: Strong, Moderate, Insufficient.
+ Statistically significant results in favor of the intervention.
n.s.: non statistically significant results.

The meta-analysis approach showed lower days of hospitaliza-
tion in the intervention group compared with usual care (MD -2.22;
95 % CI -4.30, -0.140; I2 = 50.0 %, p = 0.036). (see Appendix 1 Fig. 1)
3.5.2. Influenza vaccination coverage
Two fair-quality articles examined influenza vaccination cov-
erage [42,46]. The first [42] evaluated vaccination status by
retrospective chart review for each patient in a physician–nurse
practice while the second [46] the influenza immunization in COPD
patients in the previous 15 months in a community-based primary
care setting. As both studies found a statistically significant increase
in vaccination coverage for influenza and were of fair quality the
rating system rated a moderate evidence (Table 5).
3.5.3. Diabetic foot examination
Two studies, 1 of good-quality [44] and 1 of fair quality [42]
were focused on diabetic foot screening. Choe et al. [44] docu-
mented monofilament examination for neuropathy occurred more
frequently among those in the intervention group compared with
the control group (p = 0.002).
In the study by Litaker et al. [42] the number of patients in the
intervention group, subjected to foot examination, is statistically
higher than that in the control group (p < 0.001), reflecting the pro-
cess and quality of care carried out by the team. Although consistent
findings were found in one good-quality study and one fair-quality
study, the level of evidence was moderate (Table 5).
3.5.4. Retinal examination
Of 3 studies [42,44,46] that analyzed retinal screening among
diabetic patients, one was of good-quality [44]. Since less than 75 %
of the studies reported the same conclusions, the application of the
rating system reached an insufficient level of evidence (Table 5).
3.5.5. Medication adherence
One good-quality [29] and 1 fair-quality [42] study assessed
treatment adherence not reaching the same conclusions. Hence,
the rating system rated insufficient evidence (Table 5).
3.6. Patient reported outcomes
3.6.1. Specific quality-of-life instruments
Three studies of good quality [28,30,33] reported results on
changes of Quality of Life (QoL) using condition-specific Patient
Reported Outcome Measures (PROMs) as: Chronic Heart Fail-

198
D. Pascucci et al.
ure Questionnaire [28], Minnesota Living With Heart Failure
Questionnaire [30], St. George’s Respiratory Questionnaire [33].
A statistically significant improvement in the total score was
observed in the intervention group from baseline to follow-up in all
the three considered studies. Additionally, a statistically significant
improvement was observed in all the domains of the questionnaires
in the studies conducted by Rich et al. [28] and Kasper et al. [30]
(Table 5).
3.6.2. Generic quality-of-life instruments
Four studies of good quality [29,31,36,47] and 2 studies of fair
quality [42,46] evaluated QoL with generic PROMs. For all the ques-
tionnaires the final score was analyzed, including all the items that
made it up. Five articles [29,31,42,46,47] used SF-36 or SF-12. The
study by Von Korff et al. [36] was the only that assessed QoL as a
primary outcome with Global Quality of Life Rating, exploring both
the physical functioning and mental wellbeing and showing a sta-
tistically significant improvement from baseline. Nevertheless, the
rating system showed insufficient evidence because of inconsistent
findings in multiple good quality studies [29,31,36,47] (Table 5).
4. Discussion
The aim of this research was to conduct a systematic review of
the existing literature regarding the impact of IPC compared with
usual care on clinical outcomes, clinical process measures and PROs
for patients diagnosed with chronic diseases, excluding those with
comorbid psychiatric diagnoses, chronic functional pain and termi-
nal illness. This review provides a number of positive findings for
clinical outcomes related to IPC. As the meta-analysis results high-
lighted, there was a significant reduction in the levels of SBP, DBP,
HbA1c, and LDL and in the duration of hospitalization.
There was also strong evidence supporting the decrease in
smoking with moderate evidence documenting an improvement
for clinical process outcomes: influenza vaccination coverage and
diabetic foot examination.
There was insufficient evidence supporting IPC regarding
mortality, incidence of ESRD, retinal examination, medication
adherence, and PROs, through the application of the rating sys-
tem, due to inconsistent findings. Stratification by type of disease
of patients did not influence the effectiveness of the intervention
between the various subgroups except for the reduction of LDL lev-
els which appeared to be larger among patients with CKD. This
proved that IPC was a useful model in chronic patient management
regardless of the prevalent disease considered.
The stratifications by sample size ≥ 250, follow up < 12 months
and drop-out rate < 20 % variables had a different level of influence
on the meta-analyzed clinical outcomes, with the only exception
being for LDL. The result for the sample size ≥ 250 indicator is in
line with what stated in the scientific literature according to which a
larger sample size contributes to increase the statistical power and
avoiding Type II error [51]. Conversely, the result for the follow-up
< 12 months indicator limits the applicability and validity of the
findings and fails to capture long-term hazards which may take
years to appear, although the studies included in the meta-analysis
considered elderly people with a low life expectancy.
The presence of a pharmacist, both in meta-analysis results and
in studies not included in the quantitative synthesis, was important
in the identification and management of cardiovascular risk factors
(i.e. level of blood pressure, smoking cessation), in the assessment
of medication adherence [52,53] and in the provision of lifestyle
advices, in some cases supported also by the use of telehealth [54].
Indeed pharmacists, given the difficulties in accessing primary care
physicians for patients, are the healthcare professionals who most
frequently see patients with chronic conditions.
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Health Policy 125 (2021) 191–202
Several indicators used for the meta-analysis appeared to be
influenced by the absence of blindness (of both researchers and par-
ticipants) in the trials. The reason for this absence could be probably
found, at least partly, in the nature of some types of intervention
found which makes blindness of participants not feasible [44].
This absence is universally recognized as cause of bias [55],
especially when dealing with subjective outcomes [56], and some
authors have stated it in discussions [57]. Indeed, the knowledge of
the intervention the patient is assigned to might lead to differen-
tial behaviors by patients and health professionals, and thus affect
outcome estimates and their assessment by investigators [58], in
particular with increased risk of reporting bias [59] and observer
bias [60]. Successful and appropriate blinding is expected to avoid
contamination (application of an intervention different from the
one that specific patient was intended to receive), changes to non-
protocol interventions or lack of adherence by patients [58].
In the majority of cases, the presence of educational interven-
tions and motivational support had no effect on the results. This
probably can be due either to the pathophysiological conditions of
the recruited patients, often elderly and with dementia, or to the
lack of engagement interventions that make patients completely
aware of their health and care conditions, or to the absence of
qualified personnel for these strategies [61].
Evidence on the effect of the IPC on mortality was insuffi-
cient. The vast majority of included studies reported a lower total
number of deaths in the intervention group with respect to the con-
trol group; however, statistical significance was achieved in only
two studies [38,39]. These inconsistent findings could be related
to the heterogeneity of the adopted indicators. In addition, the
assessment of mortality for all causes may not properly catch the
differences between the groups since there could be a possible
overestimation of the effect due to confounding variables.
The overvalue is linked to the old age of individuals and the pres-
ence of comorbidities and frailties. Nonetheless, in the assessment
of the disease-specific mortality there could be misclassifications
correlated to the certification of the true cause of death [62].
Nevertheless, since all-cause mortality is not affected by bias in
classifying the cause of death, it should be examined jointly with
the disease-specific mortality in randomized trials evaluations [63].
The reduction of Length of Stay (LOS) is in line with what
previously reported by Von Grootven et al. which analyzed the
effect of a multidisciplinary approach in a geriatric context [64]. An
improvement in collaboration and communication among health-
care professionals may lead to a decrease of LOS and consequent
cost savings.
However, according to Preen et al. [35] LOS did not signifi-
cantly differ between intervention and control groups because of
the increasing pressure on bed availability within hospitals.
It was noteworthy that the results of the semi-quantitative anal-
ysis for the QoL suggested that evidence was insufficiently rated if
generic PROMs were used, while it was strongly rated in case of
adoption of disease-specific questionnaires. The aforementioned
results are further confirmed by Patick et al. [65], who underlined
that specific tools are more sensitive in detecting and quantify-
ing even small changes in health-related quality of life, although
it could be useful to adopt both generic and specific types of mea-
sures, in a complementary manner rather than in a conflicting one
[66].
Meta-analysis is a statistical method used to evaluate the
consistency of effect across a wider range of populations and
interventions to improve accuracy. Adopting this method leads to
benefits as a consolidated and quantitative review of a large and
often complex body of literature; increased sample size and the
power that allows to study the effects of interest by combining pri-
mary studies; transparency of statistical analysis; and resolution of
conflicts and uncertainties among primary studies. Meta-analyses
D. Pascucci et al.
with a rigorous and analytically approach are essential tools to be
adopted in evidence-based medicine [24].
The implications of this study suggest that greater clarity in
describing the process of the interprofessional collaboration would
go a long way to linking interprofessional collaboration with health
and/or patient outcomes. Greater specificity about the frequency of
team meetings, the mode of team communication (e.g. in person
team meetings, how often teams consulted with each other, other
types of contact, etc.) as well as the roles and responsibilities of the
team members would better support any future decision related to
staffing, reimbursement or quality assurance.
Furthermore, the evidence are stronger when the attention is
on the monitoring of transitions and continuity of care [34], taking
advantage of the clinical pathways that could be described as coor-
dinating and integrating tools to favor the continuity of care, the
training of healthcare professionals, the search of the best ways for
an efficient utilization of scarce resources, and the development of
protocols shared between hospital and primary care organizations
[67].
4.1. Strengths and limitations
This systematic review and meta-analysis has several strengths
and weaknesses that must be considered. The rigorous literature
review and meticulous study quality assessment that were con-
ducted are two strengths of this study.
The studies used for pooled analyses showed a significant het-
erogeneity, even though it is inevitable because of clinical and
methodological (i.e. care setting and type of intervention) diversity.
Nevertheless, the evidence is based on the meta-analysis of RCTs
due to their lower risk of bias and strictly inclusion and exclusion
criteria.
It is fundamental to highlight that the lack of uniformity among
the remaining indicators hindered the possibility to carry out
a quantitative evaluation through a meta-analysis, although the
implementation of the rating system proposed by Hoogendoorn
et al. [27], extensively used in the scientific literature [68,69],
allowed to run a semi-quantitative assessment via the evaluation
of the evidence level.
Furthermore, only two studies [28,42] focused on the chronic-
ity management in hospital setting. Anyhow, these studies did not
influence the conclusions since the relative findings were in line
with those of the other studies included in this revision.
4.2. Further research issues
What remains to be answered is the question, “to what extent do
those practicing collaborative care receive interprofessional education
or training”.
IPE has made a lot of progress down the long winding road that
Hall and Weaver [70] first spoke about more than 20 years ago, but
the crucial next step demands nothing less.
There are clear implications for future research that estab-
lishes the link between education and practice across all levels
of both health care education and health care delivery systems.
Future research on education and practice must articulate better
descriptions of the components of the education experiences of the
professional, as well as the resulting collaborative practice. Greater
explication of the pedagogical and theoretical foundation of the
program, the curriculum and mode and intensity of the education
intervention is needed. When this systemic approach occurs, future
research will have greater success establishing the link between
education, collaborative practice and individual and population
health outcomes.
Additionally, commitment among interprofessional stakehold-
ers, funders, and policy makers is fundamental to allocate resources
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Health Policy 125 (2021) 191–202
to structured studies about the association between IPE and col-
laborative behavior. The studies should take into account the
development of a widespread consensus on how to measure IPC
effectively throughout a range of learning environments, patient
populations, and practice settings [18].
The paucity of published research linking IPE with IPC and ulti-
mately both with patient level outcomes that limited this review
will only be achieved through the strategic application of all the
original 6-steps of Bloom’s Taxonomy for learning: Knowledge,
Comprehension, Application, Analysis, Synthesis, and Evaluation
[71].
To paraphrase Malcom Cox from his plenary address at the Col-
laborating Across Borders Conference 2017 [72], Interprofessional
Education is treated as the ‘guest’ when in fact it is the host, from
which interprofessional collaboration and eventually patient out-
comes are produced. This can be accomplished with the integration
of the multiple systems responsible for the training/education and
certification of health care professionals and the systems responsi-
ble for the delivery, reimbursement, and quality of care.
Moreover, future studies examining indicators of cost-efficacy
to evaluate the real impact of IPC on the management of chronic
patients are strongly recommended and it would be auspicious that
healthcare organizations adopt a set of robust and validated indi-
cators to cyclically assess the effect of IPC in order to confirm their
proper functioning.
5. Conclusions
A number of positive findings for clinical and process outcomes
related to IPC were found reflecting an improvement of quality of
care of chronic conditions and an enhancement in the delivery of
patient centered and coordinated care. In a period of time charac-
terized by an increasingly ageing population, scarce resources and
a health expenditure accounting for 70–80% for chronic illnesses
management [73], policy makers and administrators should allo-
cate funds [13] to favor the development of technological networks
and to establish an educational lever in support of the collaborative
approach. They may also focus on the creation of innovative clini-
cal pathways [74] and proper guidelines to improve the quality and
safety of patient care and to ease the collaborative management of
chronicities.
Moreover, the need for a purposeful systemic approach linking
interprofessional education with interprofessional collaboration
and patient health and wellbeing is necessary.
Funding sources
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
Declaration of Competing Interest
The authors report no declarations of interest.
CRediT authorship contribution statement
Domenico Pascucci: Conceptualization, Methodology, Investi-
gation, Resources, Data curation, Writing - original draft, Writing
- review & editing, Visualization, Project administration. Michele
Sassano: Methodology, Formal analysis, Resources, Data curation,
Writing - review & editing, Visualization. Mario Cesare Nurchis:
Methodology, Investigation, Resources, Data curation, Writing -
original draft, Writing - review & editing, Visualization. Michela
Cicconi: Resources, Writing - original draft, Writing - review &
editing, Visualization. Anna Acampora: Resources, Writing - orig-
D. Pascucci et al.
inal draft, Writing - review & editing, Visualization. Daejun Park:
Resources, Writing - original draft, Writing - review & editing, Visu-
alization. Carmen Morano: Conceptualization, Validation, Writing
- review & editing, Visualization, Supervision, Project administra-
tion. Gianfranco Damiani: Conceptualization, Validation, Writing
- review & editing, Visualization, Supervision, Project administra-
tion.
Appendix A. Supplementary data
Supplementary material related to this article can be found, in
the online version, at doi:https://doi.org/10.1016/j.healthpol.2020.
12.006.
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