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<article xmlns:xlink="http://www.w3.org/1999/xlink">
  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>A Robust Model for Integration of Artificial Intelligence Methods in Primary Care</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Dolgikh</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>National Aviation University</institution>
          ,
          <addr-line>Komarova Ave., 1, 03058, Kiev, Ukraine Solana Networks, 301 Moodie Dr., Ottawa, K2H9C4</addr-line>
          ,
          <country country="CA">Canada</country>
        </aff>
      </contrib-group>
      <abstract>
        <p>The cost of patient care is rapidly increasing in the developed world and improving accuracy of screening and diagnostic testing as well as other areas of primary care can provide noticeable improvements in the recovery and cost efficiency of the health care systems. In this study the authors propose a simple yet robust model of parallel decision making incorporating machine and human expert competences whereby the strengths and advantages of Artificial Intelligence methods can be harnessed to improve the overall accuracy of essential testing, diagnostics and other critical areas of patient care while ensuring safety and complete human control over the course of diagnostics and treatment.</p>
      </abstract>
      <kwd-group>
        <kwd>Artificial Intelligence</kwd>
        <kwd>Diagnostics</kwd>
        <kwd>Primary care</kwd>
        <kwd>Decision making models</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>-</title>
      <p>
        The cost of primary care is rapidly increasing in the developed world and the
accuracy of screening and diagnostic testing is one of the essential factors in the overall cost
of health care systems. The cost of misdiagnosing can be significant both in the case
of undetected serious condition resulting in prolonged recovery and higher cost of
treatment, as in the case of a false positive diagnosis leading to higher cost of
subsequent testing and possible emotional impact on the patient and their family. Directly
on the cost of direct consequences of misdiagnosis, “1 million added days in hospital
and $750 million in extra health-care spending” may be attributable to medical errors
by doctors, hospitals, and pharmacists”, according to the Canadian Institute for Health
Information's (CIHI) examination of patient safety in Canada [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ], while “improving
patient safety in US Medicare hospitals estimated to have saved US $28 billion” [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ].
High cost of diagnostics errors to the patients as well as to the primary care system
was highlighted in the World Health Organisation’s Technical Series on Safer
Primary Care report on diagnostics errors [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ].
      </p>
      <p>
        The causes of misdiagnosis are complex and while no perfect or simple solution
has been found for this serious problem, it is clear that personal and environmental
influences on the human operators in the field is one of the contributing factors. It is
well known that the performance of even professional and highly trained personnel
may vary in time and be affected by multiple factors such as physical condition,
mood, fatigue, stress and others. In particular, the burnout syndrome is well known
among professionals whose work involves conditions of high and constant stress,
responsibility for life and well-being of other people such as military personnel,
pilots, medical professionals, teachers, social workers [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ].
      </p>
      <p>
        On the other hand, the advances in the field of Artificial Intelligence technologies
over the past decades have brought the performance of machine systems in some
areas to the level of human experts, including in health care applications [
        <xref ref-type="bibr" rid="ref5 ref6">5,6</xref>
        ]. Unlike
human practitioners, machine systems offer performance on a stable level not affected
by personal and transient factors. These developments offer opportunities to
significantly improve the performance of essential diagnostics practices and procedures via
incorporation of pre-trained in the diagnostic area high performance machine
intelligence systems.
      </p>
      <p>
        However, the introduction of such complex systems in direct human care can bring
serious challenges of their own, particularly in the areas of trust and confidence in the
system that employs such components: the internal operation of complex machine
systems such as deep learning neural networks used in high accuracy image analysis
is not very well understood at the time of writing and trusting them with an essential
treatment decision can be seen as premature at this point, and less than clear if
achievable in the longer perspective. Quoting Dr Raj Jena at Addenbrooke’s hospital
in Cambridge “if you are a deep learning algorithm, when you fail you can often fail
in a very unpredictable and spectacular way”, stressing that applications of machine
intelligence systems will need robust real-world testing [
        <xref ref-type="bibr" rid="ref6 ref7">6,7</xref>
        ].
      </p>
      <p>Taking into account these challenges and opportunities, the authors undertook the
study to investigate possibilities of safe and efficient introduction of Artificial
Intelligence methods in the operational practices of primary care and proposed a simple yet
robust model whereby high accuracy machine methods can be harnessed to improve
the accuracy of essential testing, diagnostics and other critical areas of health care
without any compromised of safety, trust and confidence in the system.</p>
      <p>The motivation for this study is:
− to investigate opportunities and models of incorporating high performance
Artificial Intelligence methods into the diagnostics practices to improve the
accuracy and cost efficiency of essential diagnostics without compromising
safety, trust and confidence in the system, and
− to propose a general approach to incorporating machine intelligence systems
with the potential to measurably improve the diagnostics outcomes while
complying with the requirements of safety and full human control over the
processes of diagnostics and treatment.</p>
    </sec>
    <sec id="sec-2">
      <title>Background: Challenges and Shortcomings of the Current</title>
    </sec>
    <sec id="sec-3">
      <title>Practice</title>
      <p>
        In many health care systems and institutions, both private and public, the diagnostics
following an essential test is performed by a single human practitioner and passed on
to the next stage in the patient care chain that often takes it as a given with no further
feedback or analysis [
        <xref ref-type="bibr" rid="ref1 ref3">1,3</xref>
        ]. This practice may create a single link chain model in
which the accuracy of the entire chain is dependent and determined by that of a single
link, with correct diagnostics playing primary and sometimes critical role in the
outcome of the treatment.
      </p>
      <p>The logical consequence of this observation is that the efficiency of the chain
cannot exceed that of any single link, and the error rate in the diagnostics phase may
drive down the overall efficiency, both in terms of the patient outcome and the cost to
the system, of the entire chain.
On the other hand, the ability to reduce the incidence of essential errors is limited by
the factors of human nature that is essentially impacted by the condition and the
environment; and the cost and resource limitations in the system that do not allow
significant duplication of processes to reduce the overall error. For example, to reduce the
single link error, the system would need a second opinion on every diagnostics test or
decision, resulting in the doubling of the cost of the diagnostics system, the direction
that is rarely acceptable.</p>
      <p>The advances in machine intelligence methods and systems over the last decade
can offer an avenue toward a solution of this complex and costly problem as the cost
of deploying a pre-trained in a specific diagnostics area high accuracy and high
performance machine intelligence component can be negligible compared to educating
and hiring hundreds of human practitioners, and its performance is more stable and
not affected as much by internal or environment factors.</p>
      <p>
        However, as mentioned earlier, any such development must be cautious and deal
with the issues of trust and confidence in machine based decision-making systems
that at this time cannot be taken for granted [
        <xref ref-type="bibr" rid="ref6">6</xref>
        ]. The challenge therefore lies in
creat3.1
True
True
True
False
      </p>
      <p>Conflict, X</p>
      <p>False
True
True</p>
      <p>False</p>
      <p>D = S(C1, … Cn)</p>
      <p>S(C1,..Cn) = OR (C1, .. Cn)
In the simplest case, the channel decisions can have Boolean value of True (condition
detected) or False (normal, no condition) and one of the simplest forms of the
cumulative function could be the logical OR of the channel decisions:
Similarly to the cumulative function, the “conflict function” is defined as another
perspective on the cumulative set of the decisions of the channels, that in the simplest
form can be defined as the logical sum of pair-wise comparisons of the channel
decisions:</p>
      <p>X(C1, ..Cn) = OR((C1 == C2), (C1 == C3) ..)
Thus, the meaning of the cumulative function is: “at least one channel has detected
the condition” and that of the conflict function, “there’s at least one conflict between
the decisions of the channels”. These definitions are summarized in Table 1.
ing combined, hybrid human-machine expertise decision-making models that would
be able to combine the benefits of accuracy, high performance and stability offered by
machine systems with trust and confidence of complete and uncompromised human
control over the outcome of the diagnostics and treatment. Such an approach is
investigated and proposed in this study.</p>
    </sec>
    <sec id="sec-4">
      <title>Multi-Channel Parallel Decision-Making Model</title>
      <sec id="sec-4-1">
        <title>Decision Functions: Cumulative and Conflict</title>
        <p>Let’s suppose a decision-making system has multiple decision making channels C1, ..
Cn and the final decision will be obtained from the partial decisions of the channels by
a certain summation process that can be described by a “cumulative function” taking
as input the partial decisions of the channels and producing the final decision:
True
True
False</p>
        <p>False
3.2</p>
      </sec>
      <sec id="sec-4-2">
        <title>Accuracy</title>
        <p>True
False
True</p>
        <p>False
In the next step the accuracy of the channels and how it affects the accuracy of the
system as a whole will be analyzed. Suppose the mean accuracies of the two channels
are A1 and A2, respectively. It easily follows from the definitions of cumulative and
conflict functions above that the probabilities of an agreement (no conflict) and a
conflict of the channels under that assumption will be as follows:</p>
        <p>Pagr = A1 × A2 + (1-A1) × (1-A2) = 1 + 2 A1×A2 - (A1+A2)</p>
        <p>Pconf = A1 × (1-A2) + A2 × (1-A1) = A1 + A2 - 2 A1×A2,
(1)
and obviously,</p>
        <p>Pconf = 1 - Pagr
We shall now introduce into the model the third channel, sequential to the parallel
channels C1 and C2 that takes the input of the channels as well as values of S and X
and produces the final decision:
(2)
(3)
Finally, from (1) and (2) one can estimate the overall error in the three-channel
system as:</p>
        <p>Etot = (1-A1) × (1-A2) + Pconf × (1-A3)
The further constraint that will be imposed in this model is that the final “expert”
channel will be involved only in the case of a conflict between the parallel channels,
that is, if X(C1, C2) = True. It will also be assumed that the accuracy of the expert
channel A3 &gt; A1, A2.</p>
        <p>From (1) the probability of the correct decision of the expert channel can then be
calculated as:
and the error of the expert channel, as:</p>
        <p>Pexp = Pconf × A3</p>
        <p>Eexp = Pconf × (1-A3)</p>
      </sec>
    </sec>
    <sec id="sec-5">
      <title>ML Applications in a Multi-Channel Hybrid System</title>
      <p>In this section the authors shall apply the analysis of the multi-channel decision
making system defined in the previous section in a real-world diagnostics system
composed of the following elements:
1. A human diagnostic practitioner trained in the diagnostics domain, representing the
first channel of the parallel channel decision-making system, characterized by a
certain mean accuracy of decision A1
2. A machine intelligence system pre-trained in the diagnostic domain representing
the second parallel channel of the decision-making system with mean accuracy of A2
3. A data collection and processing unit that combines the results of the channels
producing the cumulative and conflict outputs as described in the previous section.
4. An expert human practitioner called to make the final decision in the case of a
conflict between the channels as described in the previous section.</p>
      <p>
        Also, the additional assumptions are:
a) On average, the accuracies of the human and machine channels are in the same
range [
        <xref ref-type="bibr" rid="ref5 ref6">5,6</xref>
        ], and
b) The accuracy of the expert channel in the final stage of the model is higher than
that of either of the human or the machine channels in the parallel stage.
      </p>
      <p>A system designed in this way may have a number of essential advantages over the
traditional single-chain model described in Section 2. First, it wouldn’t introduce
significant overhead in time or effort, other than in the cases where such an exercise
would be justified by the complexity of the case. If both human and machine channels
agree on the initial assessment, the expert channel will not be involved. And due to
high operational efficiency of the machine system and the fact that it can be used in
the 24 × 365 regime, in most cases its result would be ready for evaluation well before
those of the human practitioner, whereas the time and the additional cost of
combining the results of the channels in a modern computer system can be evaluated as
negligible.</p>
      <p>Secondly, such a system allows to free the highly knowledgeable and high demand
expert resources only for the most challenging cases where higher level of expertise is
warranted. Such limited resources can be involved in a highly efficient distributed
organization on a regional or even national level with remote access to all necessary
data, tests and case history.</p>
      <p>Thirdly, as will be reported in the results section it allows to substantially increase
the overall accuracy of the diagnostics process through combining human and
machine expertise in parallel decision-making channels resulting in measurable reduction
of the overall incidence of errors in the diagnosis phase and as a direct consequence
noted in the aforementioned studies, improving the outcome as well as cost efficiency
of the entire treatment chain.</p>
      <p>Finally, it is worth mentioning that the marginal cost of deployment of a
pretrained and pre-tested in the given diagnostics area machine intelligence system can
be minimal, comparable to that of a routine operation of installing or upgrading
software packages thus offering a measurable addition of value and quality of care with
minimal extra cost.</p>
    </sec>
    <sec id="sec-6">
      <title>Results</title>
      <p>In this section the authors report the estimations of the gain in accuracy of the final
diagnostics decision based on realistic values of the current diagnostics accuracy
reported in the literature.</p>
      <p>
        In this analysis, following [
        <xref ref-type="bibr" rid="ref5">5</xref>
        ] and other reports it will be assumed that in the
diagnostics domain of interest the accuracy of machine intelligence system has reached or
approached the average accuracy of a qualified, but not necessarily expert human
practitioner. Thus, the machine system is considered in the analysis to be a peer to an
average human practitioner in the given diagnostics area, but not necessarily to a
distinguished expert.
      </p>
      <p>
        For application of the proposed diagnostics model and illustration of its potential
several different diagnostics areas were taken with the data on accuracy of diagnostics
procedures and incidence of errors from comprehensive studies of diagnostics errors
in primary care [
        <xref ref-type="bibr" rid="ref8 ref9">8,9</xref>
        ]:
(1) Internal conditions (e.g. COPD, Rheumatoid arthritis), 2004, [
        <xref ref-type="bibr" rid="ref9">9</xref>
        ]: diagnostic
error incidence 13%, not including false positive cases. Adjusted to 20% to
account for false positives.
(2) Asthma, [
        <xref ref-type="bibr" rid="ref8">8</xref>
        ]: diagnostic error of up to 30% within reasonable timeframe
(wrong diagnosis or no diagnosis)
(3) Mammography, [
        <xref ref-type="bibr" rid="ref9">9</xref>
        ]: 10% and above
(4) Common across multiple diagnostic areas [
        <xref ref-type="bibr" rid="ref9">9</xref>
        ]: 13-15% excluding false
positives.
      </p>
      <p>In Table 2, the multi-channel decision-making model has been applied to the above
conditions based on the analysis of the model accuracy in Section 3. As can be
observed from these results based on reported incidence of diagnostic errors, the
improvement in the accuracy of diagnostics resulting from introduction of a
multichannel decision-making system with an incorporated AI channel ranged from 8% to
13%.
These results clearly demonstrate that incorporation of machine intelligence systems
as a parallel source of opinion in the decision-making process with a human expert
follow-up can significantly improve the accuracy of diagnostics in most reviewed
areas with measurable potential benefits for the patients and for the primary care
system.</p>
    </sec>
    <sec id="sec-7">
      <title>Discussion</title>
      <p>The results reported in the previous section demonstrate that the accuracy of routine
diagnostics and the consequent outcome as well as the cost efficiency of the
diagnostics phase can be significantly improved by harnessing the capabilities and advantages
of machine intelligence systems as a parallel decision-making channel to that of a
human practitioner, as in the standard practice of the day.</p>
      <p>This conclusion, and the ensuing results are based on the assumption that the
probability distributions of channel errors are primarily independent, as illustrated in
Fig.3. In this case, the probability of a conflict between the channel can indeed be
estimated as in (3).</p>
      <p>
        The authors will attempt to justify this assumption as reasonable. Indeed, as has
been pointed by multiple studies, e.g. [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ], human performance in critical tasks is often
affected by the factors of their condition and environment which machine systems are
less dependent upon and affected by. Consequently, it can be expected that errors
caused by these factors would not be correlated between the channels.
Another cause of correlation of erroneous decisions can lie in the specifics of
education and experience of the human practitioner vs. the machine system. Again, it can
be observed, that the machine system would likely be trained with a much broader
and larger sets of data, across geographic as well as individual practice spectrum,
reducing the likelihood of correlated systematic errors with any individual human
expert. And vice versa, any systematic or system errors in development and / or
training of the machine systems are less likely to be reflected in the education and practice
of a human practitioner reducing the likelihood of correlated errors. For these reasons
the authors believe that the assumption of independence of human and machine
decision-making can be made at least as a first approximation in evaluating the accuracy
of hybrid decision-making systems with multiple parallel channels.
      </p>
      <p>Importantly, the model equally addresses both channels of potential error in the
single chain scenario: false negative cases that may cause deterioration of the
condition and the prognosis due to undetected condition, resulting in prolonged treatment,
less positive prognosis and an increase in the overall cost of treatment; and false
positive ones, that may lead to unnecessary further testing and treatment and cause
emotional discomfort to the patient and their families. In either case, if a disagreement in
the decisions between the channels is detected, the case is brought to the attention of a
leading expert in the field with improved chance of the correct decision.</p>
      <p>
        It can be noted further that in the longer term the performance, i.e. in the case
under consideration, diagnostics accuracy of machine systems can be expected to
improve further and eventually surpass not only the average but even the expert ability
of humans as has been the case with Chess and Go games [
        <xref ref-type="bibr" rid="ref10 ref11">10,11</xref>
        ], potentially
resulting in further potential gain in the overall accuracy and the resulting efficiency of the
multi-channel diagnostics models. In such an event, the efficiency and justification for
the expert channel in the proposed model can be called into question, as due to a
higher error rate it could actually reverse some of the corrections made by the more
accurate machine channel. However, at the time this possibility appears to be remote,
both in time and the state of technology.
      </p>
      <p>In conclusion one needs to comment on the monitoring of the operational
performance of the diagnostics system that is a necessary and very important phase in
applications of any automated systems especially in the areas where it can affect the
wellbeing and health of human population. As has been noted earlier in the section, one
possible source of unaccounted error in the proposed type of systems that cannot be
completely eliminated can be a systematic correlated error that may cause
simultaneous failure of the channels.</p>
      <p>An example of cases causing such systematic failures can be a subset of rare,
nonstandard, novel or substantially deviating from the norm in the diagnostics area cases
where neither the human practitioner nor the machine system have received sufficient
training or experience. While for aforementioned reasons the authors consider
possibility of such errors as reasonably low on the average across the domains, it can
certainly be an issue in specific diagnostics areas.</p>
      <p>One approach to address such systematic issues could be to trace the diagnostic
decision to the eventual outcome of the treatment. Availability and the analysis of such
data would allow to identify, track and resolve this type of systematic errors by
adding them in the curriculum and practice of both human and machine diagnostics
practitioners.
7</p>
    </sec>
    <sec id="sec-8">
      <title>Conclusion</title>
      <p>The realities of aging population are driving the cost of health care system in the
developed countries ever upwards calling for innovative approaches to increase the
efficiency of the system while retaining and enhancing its reliability, quality of care and
safety. Such opportunities can be found in harnessing the benefits of machine
intelligence methods in applications in essential patient care that can substantially improve
the accuracy of the diagnostics systems while retaining full control over its operation.
The proposed model of combining human and machine expertise into a single
synergetic operational system offers a number of significant advantages over the traditional
“single-chain” models:
- demonstrated significant improvement in overall accuracy of diagnostics resulting
in reduction in unnecessary spending and improved patient care;
- with minimal incremental cost of development and deployment;
- flexible: the model can be easily adaptable and transferrable to different areas of
patient care;
- does not introduce any additional delay due to high performance of the parallel
machine channel;
- allows the optimal use of the expert resources only in the cases that require their
attention and involvement;
- fully compatible with distributed, high performance and outstanding quality service
delivery operational models;
- combines strengths and advantages of the human and machine expertise for a
significant improvement to the current practice;
- while retaining complete and uncompromised human control over the diagnostics
and treatment.</p>
      <p>The authors believe and fully expect that development and introduction into
operational practice of primary care of hybrid and synergetic human-machine service
delivery models of the proposed type and ones similar to it in the near future will have the
potential to significant improve the quality, reliability, safety and efficiency of the
patient care systems and may facilitate new ideas and approaches in further research,
development and improvements in operational practice in this essential for the
continuous well-being of the society field.</p>
    </sec>
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