\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Pharmacist Integration into the Hemophilia Treatment Centre: A Canadian
Pilot Project to Optimize Treatment and Improve Cost-savings}



\author[1]{Jameason Cameron}%
\author[1]{Nisha Varughese}%
\author[2]{Sylvain Grenier}%
\author[1]{Damien Roux}%
\author[1]{Robert Klaassen}%
\author[1]{Alex Wong}%
\author[2]{Caitlin Jones}%
\author[2]{Sarah Jennings}%
\author[2]{Utsav Patel}%
\author[2]{Simmi Sidhu}%
\author[1]{Regis Vaillancourt}%
\affil[1]{Children's Hospital of Eastern Ontario Research Institute}%
\affil[2]{Canadian Blood Services}%


\vspace{-1em}



  
  \date{May 22, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Coagulation factors used in prophylactic treatment of patients with
clotting disorders are associated with significant costs to health care
systems. These products have complex pharmacokinetic profiles subject to
large inter-individual variation making their efficient use challenging.
Prior to this project, pharmacists were not involved as part of the
Hemophilia care teams across Canada. The purpose of this pilot project
was to determine whether employment of a pharmacist with expertise and a
focus on plasma protein and related products including hemophilia
treatments, would be an effective strategy to reduce costs associated
with clotting factor prophylaxis regimens and identify the pharmacist's
activities associated with this new role. A cost-minimization analysis
was conducted to compare the addition of a pharmacist to the care team
of the Hemophilia Treatment Centre (HTC) at a pediatric hospital serving
500,000 children and youth. The analysis was performed from the
perspective of the formulary manager, Canadian Blood Services, over a
1-year period including 9 months of interventions. The pharmacist
performed 18 therapeutic optimizations on 14 patients with moderate to
severe hemophilia A or B, and 1 von Willebrand patient, aged 3 to 18
years old. As a result of the pharmacist's intervention, clotting factor
treatment costs extrapolated over one year were reduced by 20.5\% for
these patients. This represents a net savings of \$225K CAD/year, or
\$12.5K CAD/optimization/year. The addition of a pharmacist to the HTC
to manage recombinant and plasma-derived coagulation factors can
optimise the treatment plan and significantly reduce the costs of
managing patients with hemophilia.%
\end{abstract}%



\sloppy


\textbf{Pharmacist Integration into the Hemophilia Treatment Centre: A
Canadian Pilot Project to Optimize Treatment and Improve Cost-savings}

Varughese, Nisha\textsuperscript{1}, Grenier,
Sylvain\textsuperscript{2}, Roux, Damien\textsuperscript{1}, Klaassen,
Robert\textsuperscript{1}, Wong, Alex\textsuperscript{1}, Jones,
Caitlin\textsuperscript{2}, Jennings, Sarah\textsuperscript{2}, Patel,
Utsav\textsuperscript{2}, Sidhu, Simmi\textsuperscript{2}, Cameron,
Jameason, D.\textsuperscript{1}, and Vaillancourt,
R\selectlanguage{ngerman}égis\textsuperscript{1}

\textsuperscript{1}Children's Hospital of Eastern Ontario, Ottawa, ONT,
Canada

\textsuperscript{2} Canadian Blood Services, Medical Affairs and
Innovation

Corresponding Author:

Dr. Nisha Varughese, PharmD, BCPPS

CHEO \textbar{} 401 Smyth Road Ottawa (ON) K1H 8L1

Phone: (613) 737-7600 ext 3231 or (613) 851-6656 (M)

Email:

Co-Authors:

Sylvain Grenier,~CD, B Pharm, PharmD, FFIP, FOPQ

Canadian Blood Services, Medical Affairs and Innovation

Phone:~~(613) 739-2065

Email~:

Damien Roux

Children's Hospital of Eastern Ontario, Department of Pharmacy

Email~: damien.roux@etu.univ-lyon1.fr

Robert Klaassen, MD,~FRCP(C)

Karpinski Klaassen Medicine Professional Corporation

Professor, Department of Pediatrics

Division of Hematology/Oncology

University of Ottawa

Children's Hospital of Eastern Ontario

401 Smyth Road Ottawa, Ontario~KIH 8L1

Phone: (613) 737-2393 \#2210

Email~:

Alex Wong, B Pharm, PharmD

Children's Hospital of Eastern Ontario, Department of Pharmacy

Email~:

Caitlin Jones, BSc, BScPhm, RPh, PharmD, MScHQ

Canadian Blood Services, Medical Affairs and Innovation

Email : caitlin.jones@blood.ca

Sarah Jennings

Canadian Blood Services, Medical Affairs and Innovation

Phone:~~(613) 739-2065

Email~: sarah.jennings@blood.ca

Utsav Patel, B Pharm, R.Ph, PharmD

Canadian Blood Services, Medical Affairs and Innovation

Email : utsav.patel@blood.ca

Simmi Sidhu, BScPhm, MSc

Canadian Blood Services, Medical Affairs and Innovation

Email : simmi.sidhu@blood.ca

Dr. Jameason Cameron

Children's Hospital of Eastern Ontario

401 Smyth Road Ottawa, Ontario K1H 8L1

Phone~: (613) 737-7600 ext. 3449

Email:

Dr. Regis Vaillancourt

Children's Hospital of Eastern Ontario

401 Smyth Road Ottawa, Ontario K1H 8L1

Phone: (613) 841-5560 (M)

Email:

\textbf{Short Title:} Pharmacist-led Optimization of Hemophilia
Treatment

\textbf{-Text word count~: 2244}

\textbf{-Abstract word count~: 250}

\textbf{-Number Tables~: 2}

\textbf{-Number of Figures~: 0}

\textbf{-Number of references~: 10}

\textbf{Key Points}

The substitution of clotting factor products and the reduction of
administered doses undertaken by the pharmacist have resulted in
significant savings.

The current intervention demonstrated pharmacists can reduce clotting
factor treatment costs by 20.5\% (net savings of \$12,000 for each
treatment optimization).

\textbf{Keywords:} Hemophilia; Pharmacist; Prophylactic Treatment;
Recombinant; Cost-Minimization

\textbf{Abstract}

Coagulation factors used in prophylactic treatment of patients with
clotting disorders are associated with significant costs to health care
systems. These products have complex pharmacokinetic profiles subject to
large inter-individual variation making their efficient use challenging.
Prior to this project, pharmacists were not involved as part of the
Hemophilia care teams across Canada. The purpose of this pilot project
was to determine whether employment of a pharmacist with expertise and a
focus on plasma protein and related products including hemophilia
treatments, would be an effective strategy to reduce costs associated
with clotting factor prophylaxis regimens and identify the pharmacist's
activities associated with this new role. A cost-minimization analysis
was conducted to compare the addition of a pharmacist to the care team
of the Hemophilia Treatment Centre (HTC) at a pediatric hospital serving
500,000 children and youth. The analysis was performed from the
perspective of the formulary manager, Canadian Blood Services, over a
1-year period including 9 months of interventions. The pharmacist
performed 18 therapeutic optimizations on 14 patients with moderate to
severe hemophilia A or B, and 1 von Willebrand patient, aged 3 to 18
years old. As a result of the pharmacist's intervention, clotting factor
treatment costs extrapolated over one year were reduced by 20.5\% for
these patients. This represents a net savings of \$225K CAD/year, or
\$12.5K CAD/optimization/year. The addition of a pharmacist to the HTC
to manage recombinant and plasma-derived coagulation factors can
optimise the treatment plan and significantly reduce the costs of
managing patients with hemophilia.

\emph{}

1. Introduction

Prophylactic treatment with coagulation factors in patients with
hemophilia A and B reduces the number of bleeds and their consequences
on joints and organs, thus increasing the length and quality of life of
patients.\textsuperscript{1,2} Nevertheless, it is associated with
significant costs to the health care system. In Canada, coagulation
factors are purchased and distributed by Hema-Québec, for the Province
of Québec, and by Canadian Blood Services for all the other Provinces
and Territories. Funding is provided entirely by the Provincial and
Territorial governments. Whether recombinant or plasma-derived
therapies, factors are expensive drugs that follow complicated
pharmacokinetic (PK) trajectories making it a challenge to use them in
an optimal way.\textsuperscript{3}

With the introduction of new extended half-life products (EHL),
efficient management of coagulation factors has become even more
challenging. Indeed, many of these newer products have considerable
inter-individual variation in half-life,\textsuperscript{4,5} such as
the new factor VIII EHL product, Adynovate\selectlanguage{english}. Adynovate\selectlanguage{english} has been shown
in clinical trials to have a half-life that ranges from 6 to 30 hours,
depending on the patient. Thus, initiating therapy using the standard
dosing regimen, as prescribed in the product monograph, rather than
optimising the individual treatment plan is very cost inefficient.
Effective management of these products therefore requires tailoring
treatment to the patient. To do so, it is essential to assess and
interpret the PK profiles of patients. Recently, the Web-Accessible
Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo) web-based
platform based at McMaster University, which allows individual PK
assessments on a limited number of plasma samples, has become readily
available for clinicians to use\textsuperscript{7}. At Children's
Hospital of Eastern Ontario (CHEO), we have started to routinely perform
PK assessments for hemophilia patients, particularly when the type of
product is changed, but not systematically due to ressource limitations,
including time constraints.

To be performed systematically, PK assessment and interpretation
requires sufficient time to make extensive arrangements, ensure patient
availability and coordinate a time to review the data and results with
the care team. A dedicated pharmacist could greatly assist this process
by standardizing the approach and assisting with the interpretation of
the PK results. Since the therapy for patients with moderate to severe
hemophilia costs \$50,000-500,000 CAD/year/patient, small changes could
result in significant cost savings. For instance, two US studies have
shown that involvement of a pharmacist in the management of recombinant
and plasma derived factor therapies for hemophilia improves patient
management and reduces associated costs.\textsuperscript{8,9}

As in Canada, in the US pharmacists are not typically part of the
comprehensive care team for the hemophilia population. The Hemophilia
Management Program\textsuperscript{8} and The Factor Stewardship
Program\textsuperscript{9} were conducted to evaluate the impact of
including a pharmacist in the management of hemophilia patients. This
gave the pharmacist the opportunity to participate in rounds,
multidisciplinary meetings and regular patient assessments. Due to this
close contact with patients and collaboration with the team, the
pharmacist was able to identify and propose therapeutic optimizations,
including dose/frequency adjustments, to improve drug dispensing, drug
administration and also reduce wastage. One of the pharmacist's roles
was to provide guidelines and training to the care team in order to
increase and update the knowledge of each staff member involved in the
management of patients with hemophilia. The pharmacist was also involved
in coordinating the transition of care to the community by facilitating
the flow of information with the pharmacy service. The combination of
these activities allowed the pharmacist to improve the management of
coagulation factors in patients with clotting disorders, which led to a
reduction in the quantity of factor being used and significantly reduced
the cost associated with therapy. Thus, the implementation of a
pharmacist working as part of the transfusion medicine team in our
institution could maximize patient outcomes while minimizing the cost of
these expensive therapies.

The purpose of this pilot project was to determine whether a pharmacist
working as part of the Hemophilia Treatment Centre (HTC) would render
the management of coagulation factors more cost effective and to
identify the pharmacist's activities associated with this new role. The
intent of incorporating a pharmacist as part of the care team was to
optimise protocols and maximize cost savings through reduced wastage
while maintaining patient outcomes.

2.Materials and Methods

This project occurred at the Children's Hospital of Eastern Ontario
(CHEO), Canada, which specializes in pediatric care, with over 6,700
annual admissions, serving a population of 500,000 children and youth.
CHEO patients with moderate to severe hemophilia A or B or von
Willebrand disease (vWD) receiving prophylactic treatment with
recombinant or plasma-derived clotting factor were eligible for a
pharmacist assessment.

\emph{2.1 Model design}

We conducted a cost-minimization design study to determine the most
cost-effective clotting factor management strategy for patients
receiving prophylactic treatment. We compared the pre-intervention
strategy, current model of care without pharmacist involvement, to the
post- intervention strategy, model of care that included pharmacist
interventions and support. We assumed that the effectiveness of both
strategies was the same. The study was conducted from the perspective of
the formulary manager, Canadian Blood Services, with a one-year time
horizon.

\emph{2.2 Model inputs}

Only drug prices were considered since it has been shown that more than
97\% of the cost is due to clotting factor
replacement\textsuperscript{10}. Other sources of costs, such as drug
administration and storage costs, do not substantially impact on the
overall cost. Due to the confidential nature of the cost of coagulation
factors, the financial calculation was done by Canadian Blood Services.
The unit cost of each product was used and then multiplied by the units
projected to be consumed annually for each patient. Since the unit costs
are proprietary information, the doses and unit costs will not be
disclosed, only the annual cost savings per patient will be reported. We
assumed that the annual salary of a pharmacist is \$130K CAD.

\emph{2.3 Scenario}

A pharmacist was assigned for the period of 1 year. This pharmacist
began with a 3-month phase-in period during which no interventions were
done by the pharmacist, followed by 9 months of specific action on
optimization protocols with the goal of achieving cost savings while
maintaining best patient care. Training material for the pharmacist was
developed and provided by the Canadian Blood Services Plasma Protein and
Related Product Formulary Program team. The pharmacist worked in
collaboration with CHEO staff on patient level data pertaining to the
pharmacokinetics of individual treatment responses in an effort to
optimise the dose and the treatment. McMaster's WAPPS-Hemo served as the
basis for therapeutic optimization. WAPPS-Hemo generates PK profiles
that allow the pharmacist to tailor the treatment to the clotting
factor's actual profile, the targets of treatment, and the needs of the
patient.\textsuperscript{7}

\emph{2.4 Sensitivity analysis}

Since the parameters used are subject to variation, we performed one-way
and two-way sensitivity analyses to assess the robustness of our model.
We varied the cost of drugs and the pharmacist's salary and observed the
impact it would have on the project savings. Drug costs were varied by
+/-30\%. The pharmacist's salary was varied within +/-30\% of its
baseline value.

3.Results

\emph{3.1 Cost-savings}

Fourteen (14) patients aged 3 to 18 years old, with severe (12) or
moderate (2) hemophilia A (12) or B (2), and one patient with severe vWD
had their treatment optimised during the 1-year period of the projet.
The pharmacist made a total of 18 interventions to optimise therapy.

As a result of the pharmacist's interventions (\emph{Table 1} ), the
costs of coagulation factors for 15 patients with coagulation disorders
extrapolated over 1 year would be reduced by 20.5\%, representing
savings of \$355K CAD/year. After accounting for the \$130K CAD
investment for the employment of the pharmacist, this represents a total
saving of \$225K CAD/year, or an average savings of \$12.5K CAD per
optimization per year.

The largest projected savings were seen in patients initially treated
with plasma-derived factors. The seven therapeutic optimizations with
Wilate\selectlanguage{english} as the initial therapy resulted in savings of \$409K CAD, or
\$58K CAD/year per patient. Substitution of Wilate\selectlanguage{english} with Adynovate\selectlanguage{english}
generated savings of \$101K CAD/year per patient, compared with \$26K
CAD/year per patient for dose optimization of Wilate\selectlanguage{english} alone. Among the
eight hemophilia A patients who underwent product substitution, seven
were switched to Adynovate\selectlanguage{english} for a total projected savings of
approximately \$281K CAD/year. In total, product substitutions saved
\$24K CAD/year per patient while keeping the same treatment and
optimising doses saved about \$15.5K CAD/year per patient.

Insert Table 1. About Here

\emph{3.2 Sensitivity analysis}

A sensitivity analysis was conducted to analyze the effect of a +/- 30\%
variation in both drug costs and pharmacist salary (Table 2 ). In the
worst-case scenario where there is a combination of a 30\% decrease in
drug cost and a 30\% increase in the pharmacist's salary, there is still
a net savings of \$79.5K CAD/year. There would have to be a 63\%
reduction in drug costs or a 173\% increase in pharmacist salary for the
cost-effectiveness of adding a pharmacist as part of the transfusion
medicine team to be lost. These drastic changes in drug cost and
pharmacist salaries are highly unlikely; therefore, the strategy of
adding a pharmacist to manage coagulation factors remains beneficial.

Insert Table 2. About Here

\emph{3.3 Pharmacist activities}

PK analyses conducted by the pharmacist consisted of entering and
analyzing factor levels, and~identifying and performing therapeutic
optimizations. These activities consumed 30\% of the pharmacist's
working time\emph{.} Given these PK assessments, two types of
optimizations were proposed: product substitution or dose optimization
with the same drug. Once identified, possible optimizations were
discussed with the physician and then proposed to the patient's family.
The pharmacist's role was not restricted to PK analyses. The most
time-consuming activity conducted by the pharmacist involved clinic
attendance which represented 40\% of the pharmacist's working time.
Clinic attendance activities included discussions with families,
education on new product administration, and discussions with the
multidisciplinary team. Furthermore, 20\% of the pharmacist's time was
dedicated to administrative activities such as organization of
appropriate switch days, coordinating laboratory tests and timing of PK
assessments, ensuring entire supply consumption, adverse event reporting
and inventory management support. Finally, the pharmacist developed
practice improvement policies and trained staff 10\% of the time.

4. Discussion

The current intervention was made possible with a novel clinical tool
(WAPPS-HEMO) that pharmacists can now use that allows individual PK
assessments to help the transfusion team optomize coagulation factors.
Findings from the current pilot study demonstrated a successful
cost-minimization model of adding a trained pharmacist as part of
personalized treatment of patients living with hemophilia receiving
prophylaxis with coagulation factors. We showed that the substitution of
clotting factor products and the reduction of administered doses
undertaken by the pharmacist have resulted in savings that were 2.7
times greater than the investment in the pharmacist's salary, savings
that were realized by only the 7th patiet optimization. Indeed, the
current intervention demonstrated pharmacists can reduce clotting factor
treatment costs by 20.5\% (net savings of \$12,000 for each treatment
optimization).

Product substitution can particularly result in significant cost
savings, but a strong understanding of PK profiles is required to make
these interventions effective. Additionally, increased support to
counsel patients and avoid product wastage is important when switching
products.\textsuperscript{5}

Slocum et al\textsuperscript{8} had previously demonstrated that the
involvement of a pharmacist in the care team for the hemophilia
population resulted in significant cost savings. Implementation of their
hemophilia management program resulted in an ROI of 20:1. This is higher
than ours, but this difference can be explained by the larger number of
patients they treat and by the higher pricing of factors in the US. In
support of our findings, this study highlighted the fact that the new
role given to the pharmacist should not be limited to therapeutic
optimization and treatment management alone. The support and counseling
of patients and families in treatment management is also important;
optimization of treatment on its own is insufficient. This is especially
true when dealing with a pediatric population. The pharmacist's
involvement as a member of the care team is crucial to improve practices
and deepen the team's knowledge of medications, thus improving the
patient's clinical outcome and reducing costs.

Due to the one-year time horizon, we were unable to measure long-term
outcomes and therefore assumed that patients with and without pharmacist
intervention achieved the same outcomes. It is possible that these
interventions could lead to improved outcomes such as decreased
hospitalizations, in which case more savings would be possible. Although
the pharmacist performed therapeutic optimizations for only 9 months,
given the initial 3-month phase-in period, savings were calculated on an
annual basis to obtain savings over the entire project duration. On a
longer time scale, therefore, greater annual savings could be expected.
The validity of the costs was difficult to confirm, although this was
compensated for by performing a sensitivity analysis. The small
population size could be responsible for important cost variations
between each of the optimizations made. This limitation challenged
whether it is appropriate to extrapolate the results on a larger scale.
As the study population was exclusively pediatric, the effect of
implementing such a project on adults remains unknown. However, because
the doses of clotting factor products consumed in adults are higher,
implementation of the project in the adult population could result in
significant cost savings. Following the success of this pilot project,
it will be continued in children and expanded to adults, bringing more
information to a larger number of patients and a broader age group. If
the findings in this project continue to be demonstrated, this will be
used as a case study to expand to HTCs across Canada.

Our pilot project demonstrated that involvement of a pharmacist in the
hemophilia care team allowed for significant reduction in the costs of
coagulation factor therapy in Canada. Thorough analyses of PK data,
relationships with patients and families, involvement in the care team
and development of protocols are activities that can be performed by a
pharmacist in a HTC to help improve the management of prophylactic
therapy with coagulation factors.

\textbf{References} ~:

\begin{enumerate}
\tightlist
\item
  Iorio A, Marchesini E, Marcucci M, Stobart K, Chan AKC. Clotting
  factor concentrates given to prevent bleeding and bleeding\selectlanguage{english}-related
  complications in people with hemophilia A or B. \emph{Cochrane
  Database of Systematic} \emph{Reviews} 2011; 9.
\item
  Usuba K, Price VE, Blanchette V \emph{et al} . Impact of prophylaxis
  on health-related quality of life of boys with hemophilia: An analysis
  of pooled data from 9 countries.~\emph{Research and practice in
  thrombosis and haemostasis} ~2019; \emph{3:} 397--404.
\item
  Barnes C. Importance of pharmacokinetics in the management of
  hemophilia. Pediatr. \emph{Blood Cancer} 2013; 60: 27-29.
\item
  Kontermann RE. Strategies for extended serum half-life of protein
  therapeutics. \emph{Current opinion in biotechnology} 2011; 22(6):
  868--876.
\item
  Escobar M, Santagostino E, Mancuso ME \emph{et al} . Switching
  patients in the age of long-acting recombinant products?.~\emph{Expert
  review of hematology} 2019;~\emph{12} (1): 1--13.
\item
  Croteau SE, Cheng D, Cohen AJ, et al. Regional variation and cost
  implications of prescribed extended half-life factor concentrates
  among U.S. Haemophilia Treatment Centres for patients with moderate
  and severe haemophilia. \emph{Haemophilia} 2019; 25: 668-- 675.
\item
  Hajducek DM, Chelle P, Hermans C, et al. Development and evaluation of
  the population pharmacokinetic models for FVIII and FIX concentrates
  of the WAPPS\selectlanguage{english}-Hemo project. \emph{Haemophilia} 2020; 26: 384-- 400.
\item
  Slocum GW, Peksa GD, Webb TA, Lat I. Implementation of a hemophilia
  management program improves clinical outcomes. \emph{J Am Coll Clin
  Pharm} 2018; 1--7.
\item
  Amerine LB, Chen SL, Daniels R, Key N, Eckel SF, Savage SW. Impact of
  an innovative blood factor stewardship program on drug expense and
  patient care.~\emph{American journal of health-system pharmacy :
  AJHP}2015;~\emph{72} : 1579--1584.
\item
  O'Hara J, Hughes D, Camp C, et al. The cost of severe haemophilia in
  Europe: the CHESS study. \emph{Orphanet J Rare Dis} 2017; 12: 106.
\end{enumerate}

\textbf{Acknowledgements and/or Contributions :} Vivain Ho helped with
formatting the manuscript.

\textbf{Conflicts of Interest:} The authors have no financial
relationship that relates in any way to the content of the manuscript
and have no conflicts of interest to report.

\textbf{Funding:} This research was not supported by grant funding from
any agencies in the public, commercial, or not-forprofit sectors.

\textbf{Hosted file}

\verb`Table 1_Supl File_Pharmacist_PBandC_Varughese_March 20 2023.docx`  available at \url{https://authorea.com/users/359494/articles/630861-pharmacist-integration-into-the-hemophilia-treatment-centre-a-canadian-pilot-project-to-optimize-treatment-and-improve-cost-savings}

\textbf{Hosted file}

\verb`Table 2_Supl File_Pharmacist_PBandC_Varughese_March 20 2023.docx`  available at \url{https://authorea.com/users/359494/articles/630861-pharmacist-integration-into-the-hemophilia-treatment-centre-a-canadian-pilot-project-to-optimize-treatment-and-improve-cost-savings}

\selectlanguage{english}
\FloatBarrier
\end{document}

