the clinical & economic burden of treatment resistant … · 2021. 4. 12. · aly akram erfan...

White Paper

The Clinical & Economic Burden of Treatment Resistant Depression in the GCC: The Kingdom of Saudi Arabia, Kuwait and the United Arab Emirates

MAY 2020

List of Authors

Acknowledgements

ALY AKRAMErfan and Begado General Hospital, Jeddah, KSA

MEDHAT AL-SABAHY Sheikh Khalifa Medical City, Abu Dhabi, UAE

AHMED AL-JEDAI Ministry of Health, Riyadh, KSA

HAJER ALMUDAIHEEMMinistry of Health, Riyadh, KSA

MOHAMED FARGHALLYDubai Health Care Authority, Dubai, UAE

EBTIHAJ FALLATAJeddah Psychiatric Hospital, Jeddah, KSA,

OSAMA ALIBRAHIMAlamal Hospital, Jeddah, KSA

TAREK SHOUKRYKuwait Center for Mental Health, Kuwait

SUJATA BASU IQVIA, Gurgaon, India

DANIELLE CHALOUHIJanssen GCC, Dubai, UAE

AMR ELSHARKAWYJanssen GCC, Dubai, UAE

OMNEYA MOHAMEDIQVIA, Dubai, UAE

Our thanks to Dr, Adel Kirani, Sheikh Khalifa Medical City, Abu Dhabi, UAE and Dr. Ashraf Shazly, Kuwait Center for Mental Health, Kuwait for their clinical insights and Mr. Mahmoud Awad Sheikh Khalifa Medical City, Abu Dhabi, UAE for his costing insights.

2 | The Clinical & Economic Burden of Treatment Resistant Depression in the GCC: The Kingdom of Saudi Arabia, Kuwait and the United Arab Emirates

DisclosuresConflict of interestAly Akram, Medhat Al-Sabahy, Ahmed Al-Jedai, Hajer Al-Mudaiheem, Mohamed Farghally, Ebtihaj Fallata, Ossama Alibrahim, Tarek Shoukry declare that they have not conflict of interest. Danielle Chalouhi and Amr Elsharkawy are employees of Janssen. Sujata Basu and Omneya Mohamed are employees of IQVIA AG

Funding Funding was provided by Janssen EMEA-EM to IQVIA to develop the conduct the study and to provide technical writing assistance.

iqvia.com | 3

Table of contentsList of Tables 5

List of Figures 8

Abbreviations 9

1. Introduction 10

1.1. Background 10

1.2. Objective 11

2. Methodology 12

2.1. Model structure 12

2.1.1. Patients and Perspective 13

2.1.2. Time Horizon and Discounting 13

2.1.3. Treatment Pathways 14

2.1.4. Model assumptions 16

2.1.5. Model data and inputs 16

3. Results of burden of diseases analysis 27

3.1. KSA 27

3.1.1. Base Case 27

3.1.2. Scenario analysis 31

3.2. Kuwait 35

3.2.1. Base Case 35


3.3. UAE 43

3.3.1. Base Case 43


4. Discussion and Conclusion 51

5. Limitations 52

6. Appendix 53

References 60


iqvia.com | 5

List of TablesTable 1: Definition of various health states 14

Table 2: Population inputs (KSA) 16

Table 3: Population inputs (Kuwait) 17

Table 4: Population inputs (UAE) 18

Table 5: Transition probabilities without suicidal mortalities 19

Table 6: Transition probabilities with suicidal mortalities 19

Table 7: Drug acquisition cost by class of drugs (KSA) 20

Table 8: Drug acquisition cost by class of drugs (Kuwait) 20

Table 9: Drug acquisition cost by class of drugs (UAE) 21

Table 10: Drug outpatient cost (KSA) 21

Table 11: Drug outpatient cost (Kuwait) 21

Table 12: Drug outpatient cost (UAE) 22

Table 13: Drug monitoring cost (KSA) 22

Table 14: Drug monitoring cost (Kuwait) 22

Table 15: Drug monitoring cost (UAE) 23

Table 16: Adverse events incidence rate 23

Table 17: Adverse events cost by treatment class (KSA) 24

Table 18: Adverse events cost by treatment class (Kuwait) 24

Table 19: Adverse events cost by treatment class (UAE) 24

Table 20: Indirect medical cost (KSA) 24

Table 21: Indirect medical cost (Kuwait) 25

Table 22: Indirect medical cost (UAE) 25

Table 23: Population estimates in base case 26

Table 24: Overall cost burden of TRD by line of therapy 27

Table 25: Overall cost breakdown by health state 28

Table 26: Overall costs by service provided 29

Table 27: Cost breakdown per patient (per intervention for entire time horizon) 29

Table 28: Population estimates in Scenario 1 30

Table 29: Overall cost burden of TRD by line of therapy in Scenario 1 31






















Appendix Table 1: Cost inputs breakdown per class of treatment 52

Appendix Table 2: Overall cost breakdown by health state in Scenario 1 53

Appendix Table 3: Overall costs in an aggregated and disaggregated manner in Scenario 1 53



Appendix Table 6: Breakdown of overall cost burden by health state in Scenario 1 55








iqvia.com | 7




















Appendix Table 1: Cost inputs breakdown per class of treatment 52













List of FiguresFigure 1: Key objective of the study 10

Figure 2: Model structure 12

Figure 3: TRD Treatment: Guidelines 13

Figure 4: Cost breakdown by health state 27

Figure 5: Cost bifurcation per health state 28

Figure 6: Cost breakdown by health state 36

Figure 7: Cost bifurcation per health state 36

Figure 8: Coast Breakdown by health state 44

Figure 9: Cost bifurcation of health state 44


AbbreviationsACRONYM DEFINITION

AED UAE Dirham

BP Blood Pressure

CBT Cognitive Behavioural Therapy

CHMP Committee for Medicinal Products for Human Use

DSM-5 The Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition)

ECG Electrocardiography

ECT Electroconvulsive Therapy

GaStat General Authority for Statistics

GCC Gulf Cooperation Council

GIT Gastrointestinal Tract

GLMM Gulf Labor Markets, Migration and Population

KOL Key Opinion Leader

KSA Kingdom of Saudi Arabia

KWD Kuwaiti Dinar

MADRS Montgomery–Åsberg Depression Rating Scale

MDD Major Depressive Disorder

MDD and TRD patients Major Depressive disorder patients who progressed to treatment resistant depression

MDD patients Major Depressive disorder patients with or without treatment resistant depression

NIMH National Institute of Mental Health

NUPCO National Unified Procurement Company

QALY Quality-Adjusted Life Year

SAR Saudi Riyal

SFDA Saudi Food and Drug Authority

SNRI Serotonin–Norepinephrine Reuptake Inhibitors

SSRI Selective Serotonin Reuptake Inhibitors

STAR*D Sequenced Treatment Alternatives to Relieve Depression (Trial)

TRD Treatment Resistant Depression

UAE United Arab Emirates

iqvia.com | 9

1.1. BackgroundGlobally, an increasing number of countries are facing an unusual problem. Successful efforts by policy stakeholders to improve the wellbeing of their citizens, medically and economically, have led to an almost paradoxical outcome: an emerging pandemic of chronic diseases as a major healthcare concern.

In the countries of the GCC (Gulf Cooperation Council), of these chronic diseases (which contribute to approximately 70% of all deaths),,, neuropsychiatric disorders contribute to 14 to 20% of the total burden of disease. Of these neuropsychiatric disorders, the single category of major depressive disorders (MDD) contributes to almost half of the total (42 to 45%),. While the global twelve-month prevalence of MDD is challenging to predict, it is believed to be 4.7% (4.0% in low/middle-income countries and 5.1% in high-income countries) on average. MDD itself is the second most common illness leading to disability worldwide8,. Within the GCC, MDD has an approximate prevalence of 5.1%8,.

The definition of MDD is complex. According to the National Institute of Mental Health (NIMH), in order to be diagnosed with MDD, an individual must have at least five of a selection of nine possible symptoms (and at least one of those should be “depressed mood” or “loss of interest or pleasure in activities”), experience those symptoms almost every day for at least two weeks and do so more intensely than normal (i.e. more than everyday mood fluctuations). These symptoms, as defined by the DSM-5 (The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), are as below:

DEPRESSION DSM-5 DIAGNOSTIC CRITERIA:

1. Depressed mood most of the day, almost every day, indicated by your own subjective report or by the report of others. This mood might be characterized by sadness, emptiness or hopelessness.

2. Markedly diminished interest or pleasure in all or almost all activities most of the day, nearly every day.

3. Significant weight loss when not dieting or weight gain.

4. Inability to sleep or oversleeping nearly every day.

5. Psychomotor agitation or retardation nearly every day.

6. Fatigue or loss of energy nearly every day.

7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day.

8. Diminished ability to think or concentrate, or indecisiveness, nearly every day.

9. Recurrent thoughts of death (not just fear of dying), suicide without a specific plan (known as suicidal ideation), having a specific plan for committing suicide or a suicide attempt.

The treatment of MDD is as intricate as its definition and encompasses psychotherapeutic, psychosocial and pharmacological interventions (including a variety of different classes of antidepressants; i.e. selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs)). Despite the diversity of available pharmacological and non-pharmacological treatments, approximately 30% of MDD patients do not respond to first line antidepressant therapy while 10 to 20% of MDD patients become resistant to multiples forms of therapy. This is a worrying figure, since studies suggest that treatment resistance is the major factor determining the economic burden of depression, rather than MDD severity.

This condition, where patients suffering from unipolar depressive disorder do not adequately respond to the recommended dose of at least 2 different antidepressants, is termed ‘Treatment Resistant Depression’ (TRD). The high unmet need among the TRD patients (due to the limited number of treatment options, long onset of treatment effect and the risk of suicide and other harmful behaviors) takes a profound

1. Introduction


toll on healthcare resource consumption and creates indirect costs incurred from loss of productivity and the wider societal implications of the treatment itself,:. Studies conducted in the United States (US) estimated that, not only were the annual costs for healthcare and lost productivity per patient higher for TRD compared to the treatment-responsive19, but TRD was associated with 29.3% higher costs in medical expenditures compared to MDD.

Despite the significant prevalence of TRD in the GCC and the seriousness of its impact, there is a shocking scarcity of evidence on the clinical and economic burden of TRD in the region. To gain a clearer understanding of the overall clinical and economic burden of TRD and to provide healthcare stakeholders with a mechanism to quantify the value of novel interventions, a simulation model was developed.

1.2. ObjectiveThe study was carried out in order to quantify the burden of TRD imposed on the Kingdom of Saudi Arabia (KSA), Kuwait and the United Arab Emirates (UAE) in terms of its clinical and economic impact from the payer’s perspective in each country. The clinical burden focuses on understanding available treatment options, patterns, and clinical outcomes. The economic burden looks into the epidemiology, prevalence and natural course of the disease in order to assess the cost of its management in a real-world setting. The specific aims of the project are depicted in Figure 1.

Figure 1: Key objective of the study

• Understand the epidemiology, prevalence and natural course of TRD patients in the GCC• Possible risk factors & diagnosis• Available treatment options, patterns & clinical outcomes• TRD complications & disease progression• Economic burden and cost of TRD management in real world setting

Objectives

Project’s objectives can be grouped into key focus areas:• Epidemiology and risk factors• Treatment patterns• Clinical burden• Economic burden

Scope:• KSA, Kuwait and the UAE

Key focus areas

iqvia.com | 11

2.1. Model structureMDD and TRD are complex disorders, with TRD being more complex. A group of patients may be collectively diagnosed with TRD but that does not mean that each patient will be identical. Some patients may be at the beginning of their TRD management, while others may be at the end. Some may have displayed good response to TRD treatment and are now in remission, while others may have developed suicidal ideation and succumbed to suicide, one of the possible endpoints for disease progression. To add to the complexity, over time, patients will move between one disease stage (called a health state) and another in a process known as transition. For certain states, called absorbing states, however, there is no return (i.e. death by suicide).

In order to mathematically simulate this complex (and somewhat randomly changing) system, a Markov Model is often utilized . Based on probability theory and stochastic processing, this model allows us to evaluate the potential outcomes of a disease by mapping out all the health states possible in that disease and the probability of moving between any two states (i.e. from non-response in first stage management to remission in second stage management), with one important and over-riding assumption: the future state a patient will enter is dependent only on their current state and not any other event that occurred before it. This property, called the Markov property is what allows us to distil a multifaceted process down to the level where it can aid in decision making.

The concept behind this model was based on the Sequenced Treatment Alternatives to Relieve Depression Study (STAR*D), one of the largest and most robust studies ever undertaken by the National Institute of Mental Health (NIMH). This project, a pragmatic study, was designed to allow healthcare stakeholders to generalize its results to the “real world” in a way that previous randomized-control trial studies could not. This included: utilizing minimal conditions

to be in the study, including only physician-referred patients, using an “equipoise-stratified randomization” strategy and making the pharmacotherapies open label. The overall goal of the STAR*D study was to assess the effectiveness of depression treatments in patients diagnosed with major depressive disorder. Over a seven-year period, the study enrolled 4,041 outpatients, ages 18-75 years, from 41 clinical sites around the US. The rationale for considering utilizing the transition probabilities from this study was that its four successive steps of therapy and patient population characteristics are in line with the model below.

In order to ensure the model represented the most up-to-date values available for the disease, a preliminary two parts methodology was utilized:

Phase 1: Literature ReviewAn extensive secondary data search (focusing on published literature, registries and other data sources) was conducted on a regional and country/sector-wise level, based on the following investigational points:

• Clinical Burden: natural history of TRD, etiology and risk factors, diagnostic measures, treatment mechanisms and patterns, clinical patterns (i.e. depressive episodes, response rates and suicidal ideation/attempts)

• Economic Burden: Healthcare/pharmaceutical resource utilization and their costs, productivity loss (i.e. presenteeism and absenteeism)

Phase 2: KOL ValidationThe involvement of identified Key Opinion Leaders (KOL’s) was utilized to:

• Supplement and validate the secondary data review by addressing literature gaps and verify that the academic research outcomes were a valid representation of actual ground realities (including drug availability and usage, country-specific practices and the particulars of non-pharmaceutical therapies)

2. Methodology


• Validate the subsequent model’s parameters, assumptions and structure, as well as its applicability in individual country settings

2.1.1. PATIENTS AND PERSPECTIVEThe model initiates with a TRD population defined as those adult MDD patients who have had an inadequate response (no response or partial response) to at least two different classes of antidepressants (SSRI, and SNRI).

2.1.2. TIME HORIZON AND DISCOUNTINGFor practical purposes, the model must confine itself to a limited time period, known as a time horizon, which is divided into equal increments of time called

cycles: the cycle length and time horizon used in the model were 4 weeks and 1 year, respectively. The 1-year time length was used to assess the cost of treating one treatment-resistant depressive episode without recurrences. Additionally, as pharmaceutical interventions generally take full effect only 4 weeks after initiation, the 4-week cycle was chosen. The selection of these relatively short values allowed simplification of the model, removing the need for such things as half-cycles or altering the costs due to the passage of time (i.e. cost discounting). The model structure is shown in Figure 2.

TRD population (MDD patients

with inadequate response for

two AD)

MD

D p

opul

atio

n

Combination/Augmentation

Integration

Partialresponse

Non response

Remission

Suicidal ideation

Partialresponse

Non response

Remission

Relapse

Recovery

Suicidalideation

Augmentation

Partialresponse

Non response

Remission

Relapse

Recovery

Relapse

Recovery

Suicidalideation

Suicide related death

Coun

try

Adul

t pop

ulat

ion

Figure 2: Model structure

iqvia.com | 13

2.1.3. TREATMENT PATHWAYSBased on the inputs from 24 KOL’s (including 3 purely for model concept validation) in the GCC, the treatment pathway for TRD patients includes a combination of two antidepressants, augmentation, and electroconvulsive therapy (ECT). Combination is when the patient is simultaneously treated with a combination of two antidepressants, each from a different drug class. Augmentation involves the adding of a second agent that is not an antidepressant but may enhance the antidepressant effect of the drug in use (e.g.: lithium, thyroid hormones,

pindolol, psychostimulants, atypical antipsychotics, sex hormones, anticonvulsants/mood stabilizers or dopamine agonists). Integration combines purely pharmaceutical interventions with other modes of treatment, which, in this case, is electroconvulsive therapy (ECT), a process done under general anesthesia in which “small electric currents are passed through the brain, intentionally triggering a brief seizure. ECT seems to cause changes in brain chemistry that can quickly reverse symptoms of certain mental health conditions”,.

Figure 3: TRD Treatment: Guidelines

As illustrated, upon diagnosis of TRD, there are a number of different approaches taken to managing the disorder. The strategy adopted will depend on various factors including patient level characteristics, depression sub-type, and previous therapies

• For estimating the BOD, based on the regulatory definition of TRD and the treatment guidelines, should we assume that the first line of TRD management is optimization or combination?

• Do we follow a sequential or a parallel approach for TRD management?

Maintenance

Maintenance

TRD diagnosis

MDD diagnosis

Abbrevations: AAP: Anti-Antipsychiatrics; AD: Antidepressants, aMDD: Adjunctive MDD; ECT: Electrocomulsive therapy; MDD Major depressive disorder; eTMS: Repetitive transcranial magnetic Stimulation; TRD: Treatment resistant depression; Management guidelines may vary by region and hence are not always generalizable globally

Partial Responders

Partial Responders

Responders

Responders

APA, (2010) American Psychiatric Association practice guideline for the treatment of patients with major depressive disorder

1st-line AD

2nd-line AD

Optimize Switching Combination Augmentation Integration

Non-Pharmacological Treatments

aMDD

aMDD


The patients move between 5 health states (i.e. remission, partial response, non-response, relapse, and recovery). (The definition of each health state has been provided in Table 1). At each line of therapy, patients are evaluated at the end of the first cycle of that treatment line to see who should be moved to the partial response, non-response and remission states. A partial or a non-respondent patient, assuming no deterioration in the symptoms, would move to the following line of therapy. At any step in the model, non-respondents or partial responders with deteriorating life-threatening symptoms (suicidal ideation or refusing drinks and food) move to ECT. (According to key experts’ opinion, about 17% of patients have suicidal ideation and move directly to ECT therapy

at each treatment level). The patients who reach remission are evaluated after week 16 and may relapse (in which case they move to the next line of treatment), while those who stay in remission for 6 months move to a recovery health state.

Based on key experts’ opinion, for the countries that were under study, a combination of two antidepressants (SSRI and SNRI) was considered, as 100% of the patients were treated with the SSRI and SNRI. However, for augmentation, the portion of patients treated with antipsychotic, anti-maniac, thyroid hormones, and/or anticonvulsant along with SSRI varied by country. In integration, after ECT, patients are kept on their previous line of treatment.

Table 1: Definition of various health states

Source: Möller HJ et al

TERM DEFINITION

Response • Defined as a ≥50% improvement in MADRS total score*

Relapse

• Defined as the return of/increase in depressive symptoms after a response is observed but before a patient is determined to be in remission

• The CHMP defines relapse as the re-emergence of depressive signs and/or symptoms within the index episode independent from medication status. It usually indicates that treatment duration was too short, or the dosage of treatment was insufficient

Remission • Defined as a MADRS total score ≤12 for an extended period (approximately 2 weeks)

Recovery • Defined as the reaching of a sustained response and return to normal functioning

Recurrence

• Defined as the return of MDD symptoms to those previously defined as having recovered

• The CHMP defines recurrence as a re-emergence of depressive symptoms after a time without or nearly without symptoms (remission) and without medication. It is seen as the start of a new episode

Abbreviations: CHMP: Committee for Medicinal Products for Human Use; MADRS: Montgomery–Åsberg Depression Rating Scale; MDD: major depressive disorder

iqvia.com | 15

2.1.4 MODEL ASSUMPTIONSThe key model assumptions were:

• The suicide-related mortality for the partial response health state was assumed to be half the rate for the non-response/relapse health state.

• Patients can receive any of the SSRI or SNRI agents along with the augmenting drug.

Definitions of patient populations considered for base case and scenarios in the model are as follows:

• TRD population: adults with MDD with an inadequate response (no response or partial response) to at least two antidepressants of different classes (SSRI, and SNRI)

• MDD population (including TRD): all adults with MDD in all lines of therapies irrespective of their progression towards TRD (inclusive of those who progressed to TRD)

• N.B. Only adults were considered for this study, though the definition of adult varied among countries: 18 years or above in the KSA, 16 years or above in Kuwait and 19 years or above in the UAE.

2.1.4.1 Model base case and scenarios analyzedIn the base case, the country populations included both adult expatriate and national patients with TRD.

Additionally, a series of scenario analyses were conducted to access the impact of MDD burden in the three countries.

• Scenario 1: The nationals only population with TRD

• Scenario 2: The total population including expatriates and nationals with MDD (including TRD).

2.1.5. MODEL DATA AND INPUTS2.1.5.1 Population inputsThe size of the population was based on regional reports, such as the Demographic Survey 2017 conducted by the General Authority for Statistics (GaStat) and the Gulf Labour Markets, Migration and Population (GLMM) Programme for the KSA; statistical reports for Kuwait and the Dubai Statistics Center (and EDS FZE) for the UAE27. The treatment population was calculated based on epidemiological sources and KOLs inputs.

A summary of the population inputs, such as the total population, prevalence rate of MDD, percentage of MDD patients diagnosed and treated, percentage of MDD population without psychotic features, percentage of MDD patients progressed to TRD and suicidal mortality by health states, is presented in Tables 2 to 4.


Table 2: Population inputs (KSA)

Source: 8,29,30,31

ITEM INPUT

TOTAL POPULATION

(SAUDI NATIONALS

AND EXPATRIATE PATIENTS)

SAUDI NATIONALS SOURCE

Total Saudi population, nationals and expatriates 33,413,660 20,768,627

General Authority for Statistics (GaStat), Demographic Survey 2017; Gulf Labour Markets, Migration and Population (GLMM) Programme.

% of population above 18 years of age for total Saudi population, nationals and expatriates

71% 23,723,699

% of population above age 18 years for total Saudi nationals 64% 13,291,921

Prevalence of MDD* 5.10% 1,209,909 677,888

Kessler RC, Sampson NA, Berglund P, et al. Anxious and non-anxious major depressive disorder in the World Health Organization World Mental Health Surveys. 2015;24(3):210-2268.

Percent of MDD patients diagnosed* 55.9% 676,339 378,939

HCP Quantitative Report –Capacity Assessment in KSA

Percent of MDD patients treated* 77.0% 520,781 291,783

Percent of MDD population without psychotic features* 90.0% 468,703 262,605

Percent of MDD patients progressed to TRD 21.7% 101,709 56,985

Rizvi SJ, Grima E, Tan M, et al. Treatment-resistant depression in primary care across Canada. 2014;59(7):349-35729

Suicide related Mortality

Non-response/ Relapse 0.47% 101,639 56,946

Bergfeld IO, Mantione M, Figee M, Schuurman PR, Lok A, Denys DJJoad. Treatment-resistant depression and suicidality. 2018;235:362-36730

Partial Response** 0.24%Assumed to be half of the rate for the Non-response/Relapse health state

Percent of TRD population with suicidal ideation 17%

Hunt IM, Windfuhr K, Swinson N, et al. Electroconvulsive therapy and suicide among the mentally ill in England: a national clinical survey. 2011;187(1-2):145-14931

Abbreviations: MDD: major depressive disorder; TRD: treatment resistant depression*based on HCP Quantitative Report – Capacity Assessment in KSA**based on assumption that half of the rate for the Partial Non-response/Relapse health state

iqvia.com | 17

Table 3: Population inputs (Kuwait)

Source: 8,29,30,31

ITEM INPUT

TOTAL POPULATION

(KUWAITI NATIONALS


KUWAITI NATIONALS SOURCE

Total Kuwaiti population, national and expatriate 4,621,638 1,403,113

http://stat.paci.gov.kw/englishreports/ #DataTabPlace:ColumnChartGendrGov

% of population above 16 years of age for total Kuwaiti population, national and expatriate

80% 3,697,310

% of population above 16 years of age for total Kuwaiti nationals

63% 883,961

Prevalence of MDD* 5.10% 1,209,909 677,888



HCP Quantitative Report –Capacity Assessment in KSA


Percent of MDD population without psychotic features* 90.0% 468,703 262,605

Percent of MDD patients progressed to TRD 21.7% 101,709 56,985










Table 4: Population inputs (UAE)

Source: 8,29,30,31

ITEM INPUT

TOTAL POPULATION

(UAE NATIONALS


UAE NATIONALS SOURCE

Total UAE population, national and expatriate 9,540,000 1,097,100

http://stat.paci.gov.kw/englishreports/ #DataTabPlace:ColumnChartGendrGov

% of population above 19 years of age for total UAE population, national and expatriate

78% 7,441,200

% of population above 19 years of age for total UAE nationals

78% 855,738

Prevalence of MDD* 5.10% 379,501 43,643



HCP Quantitative Report –Capacity Assessment in UAE


Percent of MDD population without psychotic Features* 95% 149,465 17,189

Percent of MDD patients progressed to TRD 21.70% 32,434 3730

Rizvi SJ, Grima E, Tan M, Rotzinger S, Lin P, et al. (2014) Treatment-resistant depression in primary care across Canada29.





Remission 0.00%

Recovery 0.00%




iqvia.com | 19

2.1.5.2 Transition probabilitiesThe transition probabilities were extracted, as recommended by regional KOL’s, from the STAR*D study which analyzed the baseline probabilities of partial response, non-response, remission and transition probabilities based on the presence or absence of suicidal mortalities27. The probabilities of patients’ transition between the different health states are based on the most used treatment levels in the three countries. Table 5 and Table 6 depict the baseline and transition probabilities without and with suicidal mortality, as applied in the model.

Table 5: Transition probabilities without suicidal mortalities

Source: 32

Table 6: Transition probabilities with suicidal mortalities

Source: 32

2.1.5.3. Time horizonThe model considers a 1-year time horizon with a cycle length of 4 weeks. The 1-year time horizon was used to assess the cost of treating one treatment-resistant depressive episode without recurrence. Additionally, as antidepressants generally only show their effect 4 weeks after treatment initiation, the 4-week cycle was chosen.

2.1.5.4. Direct medical costThe costs included in the model accounted for drug acquisition, outpatient physician visit, hospitalization, monitoring, adverse events, psychological and behavioral treatment.

BASELINE PROBABILITIES TRANSITION PROBABILITIES (WITHOUT SUICIDAL MORTALITIES)

Treatment level Partial Response Non-response Remission

Remission to Relapse (after being in the

remission state for 4 months)

Remission to Recovery (after

being in the remission state for 4 months)

Combination (level 3) 0.17 0.70 0.14 0.43 0.57

Augmentation (level 4) 0.16 0.71 0.13 0.50 0.50

Integration (level 5) 0.18 0.51 0.31 0.50 0.50

BASELINE PROBABILITIES TRANSITION PROBABILITIES (WITH SUICIDAL MORTALITIES)

Treatment level Partial Response Non-response Remission

Remission to Relapse (after being in the

remission state for 4 months)

Remission to Recovery (after

being in the remission state for 4 months)

Combination (level 3) 0.17 0.69 0.14 0.43 0.57

Integration (level 5) 1 1 1 1 1


Drug acquisition costsFor the base case, the inputs for drug acquisition costs were obtained from the Saudi Food and Drug Authority (SFDA) list prices, the Kuwaiti MOH’s Pharmaceutical & Herbal Medicines Registration and Control Administration Pricing Section and the DHA Real World Claims Data for the KSA, Kuwait and the UAE respectively. Drug acquisition costs were calculated based on the class of drugs instead of each specific therapy, as different lines of treatment have been considered as interventions. A weighted average price was calculated per intervention based on the KOLs’ insights on the proportion of molecule use per intervention (i.e. in the combination stage), KOL’s reported that 50% of patients were on SSRIs and 50% were on SNRIs, and, accordingly, the average treatment cost in the combination stage accounted for the average cost of both SSRIs and SNRI classes. In addition, within each class, a weighted average cost was calculated based on their labeled daily doses and their utilization as reported by KOL’s in their practices. Table 7 to 9 represent the summary of the drug acquisition cost by the class of drugs. Appendix Table 1 presents the breakdown of drug acquisition cost of each class.

Table 7: Drug acquisition cost by class of drugs (KSA)

Table 8: Drug acquisition cost by class of drugs (Kuwait)

TREATMENT OPTIONS AVERAGE TREATMENT COSTS

SSRI SAR 54

SNRI SAR 79

Combination of 2 AD (SSRI + SNRI) SAR 134

Augmentation (with SSRI) Antipsychotic (50%) Anti-maniac and Thyroid hormones and Anticonvulsant (50%)

SAR 152

ECT SAR 1252

CBT SAR 910

Abbreviation: AD: Antidepressant; ECT: Electroconvulsive therapy; SNRI: Serotonin and norepinephrine reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; µg: microgram


SSRI KWD 13

SNRI KWD 14

Combination of 2 AD (SSRI + SNRI) KWD 28

Augmentation (with SSRI) Antipsychotic (60%) Anticonvulsant (40%)

KWD 51

ECT KWD 1263

CBT KWD 77


iqvia.com | 21

Table 9: Drug acquisition cost by class of drugs (UAE)

Drug administration and travel cost

Most of the drugs are administered orally and the patient do not need to travel for administration. Therefore, there is no administration cost accounted in the model. However, due to lack of any published data regarding physician visit cost, the cost associated with the outpatient visits were estimated in the model based on KOL inputs as presented in Table 10 to 12:

Table 10: Drug outpatient cost (KSA)

Source: KOL inputs

Table 11: Drug outpatient cost (Kuwait)

Source: KOL inputs


SSRI AED 261

SNRI AED 193

Combination of 2 AD (SSRI + SNRI) AED 454

Augmentation (with SSRI) Antipsychotic (60%) Anticonvulsant (40%)

AED 669

ECT AED 602

CBT AED 460


CLASS OF DRUGS NUMBER OF OUTPATIENT VISIT/4 WEEKS TOTAL OUTPATIENT VISIT COST

SSRI 2 SAR 300

SNRI 2 SAR 300

Combination of 2 AD (SSRI + SNRI) NA SAR 300

CBT NA SAR 300

Abbreviations: AD: antidepressant; SNRI: Serotonin and norepinephrine reuptake inhibitors; SSRI: selective serotonin reuptake inhibitorsµg: microgram


SSRI 2 KWD 20

SNRI 2 KWD 20

Combination of 2 AD NA KWD 20

Augmentation with anti-convulsant or antipsychotic NA KWD 20

Abbreviations: AD: antidepressant; SNRI: Serotonin and norepinephrine reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors


Table 12: Drug outpatient cost (UAE)

Source: DHA Real World Claims Data

Drug monitoring cost

Table 13 to 15 describe the cost associated with drug monitoring.

Table 13: Drug monitoring cost (KSA)

Source: Literature review, KOL inputs and MOH costing sheets

Table 14: Drug monitoring cost (Kuwait)



SSRI 2 AED 1,000

SNRI 2 AED 1,000

Combination of 2 AD NA AED 1,000

Augmentation with anti-convulsant or antipsychotic NA AED 1,000

Abbreviations: AD: antidepressant; SNRI: Serotonin and norepinephrine reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors

TREATMENT OPTIONS COST BREAK DOWN COST PER TEST TOTAL MONITORING COST

Lithium

Pre-screening test

SAR 2222

Kidney function including pharmacologic intervention SAR 1360

Vital signs (Continuous BP monitoring) SAR 120

Serum electrolysis NR

Thyroid function test SAR 432

Serum lithium SAR 160

ECG SAR 150

Abbreviations: BP: blood pressure; ECG: electrocardiography; NR: not reported


Lithium

Pre-screening test

KWD 194

Kidney function including pharmacologic intervention KWD 110

Vital signs (Continuous BP monitoring) KWD 10


Thyroid function test KWD 35

Serum lithium KWD 13

ECG KWD 12


iqvia.com | 23

Table 15: Drug monitoring cost (UAE)


Adverse event costThe incidence rate of the adverse events, such as gastrointestinal tract (GIT) upset, libido decrease, weight gain and sleep disorder, were based on literature review,. The costs were calculated based on KOL inputs on the local practice in managing adverse events.

Table 16 describes the incidence rate while Tables 17, 18 and 19 present the adverse event cost associated with each treatment class.

Table 16: Adverse events incidence rate

Source: 32,33


Lithium

Pre-screening test

AED 1622

Kidney function including pharmacologic intervention AED 993

Vital signs (Continuous BP monitoring) AED 88


Thyroid function test AED 315

Serum lithium AED 117

ECG AED 110


ADVERSE EVENTSADVERSE EVENTS INCIDENCE (BY TREATMENT)

SSRI SNRI AUGMENTATION KETAMINE

GIT upset 7.95% - 1.00% -

Libido decrease 5.26% 7.14% - 4.17%

Weight gain 2.32% - 4.00% -

Sleep 6.25% 5.55% 1.90% -

Abbreviations: SNRI: Serotonin and norepinephrine reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors;


Table 17: Adverse events cost by treatment class (KSA)

Table 18: Adverse events cost by treatment class (Kuwait)

Table 19: Adverse events cost by treatment class (UAE)

2.1.5.5. Indirect costThe indirect cost of TRD “productivity lost” on the target populations was estimated from literature based on the average Gross Domestic Product (GDP) per capita,. Table 20, 21 and 22 summarize the indirect medical cost incurred.

Table 20: Indirect medical cost (KSA)

Source: 34,35

TREATMENT OPTIONS AE COSTS

SSRI SAR 27

SNRI SAR 37

Combination of 2 AD -

Augmentation with antipsychotic and Anticonvulsant -



SSRI KWD 1

SNRI KWD 1

Combination of 2 AD -

Augmentation with antipsychotic and Anticonvulsant -



SSRI AED 7

SNRI AED 9

Combination of 2 AD (SSRI+SNRI) -

Augmentation with anti-convulsant or antipsychotic -


ITEMS TOTAL COST

Forgone earnings per cycle due to Presenteeism SAR 1,591

Forgone earnings per cycle due to Absenteeism SAR 1,887

Forgone earnings per ECT Absenteeism (per cycle) SAR 954

Total SAR 4432

Abbreviation: ECT: Electroconvulsive therapy

iqvia.com | 25

Table 21: Indirect medical cost (Kuwait)

Source: 34,35

Table 22: Indirect medical cost (UAE)

Source: 34,35

ITEMS TOTAL COST

Forgone earnings per cycle due to Presenteeism KWD 183

Forgone earnings per cycle due to Absenteeism KWD 217

Forgone earnings per ECT Absenteeism (per cycle) KWD 109

Total KWD 509


ITEMS TOTAL COST

Forgone earnings per cycle due to Presenteeism AED 841

Forgone earnings per cycle due to Absenteeism AED 998

Forgone earnings per ECT Absenteeism (per cycle) AED 504

Total AED 2,344



3.1. KSA3.1.1. BASE CASEIn this base case, the model estimated that at the end of the time horizon of 1 year, KSA would have 101,639 TRD patients presenting an overall economic burden of SAR 14,997 million. Table 23 provides a summary of the population estimates, such as total adult Saudi population (nationals and expatriates), total MDD population and total TRD population for the base case for KSA.

Table 23: Population estimates in base case

Table 24 presents the overall burden and breakdown in terms of cost and number of patients at the end of the time horizon. The major driving factor of the burden of disease was the hospitalization cost (SAR 4,562 million, 30.3%).

3. Results of burden of diseases analysis

ITEM PERCENT ESTIMATES

Total Saudi population, nationals and expatriates 100% 33,413,660 General Authority for Statistics (GaStat),

Demographic Survey 2017; Gulf Labour Markets, Migration and Population (GLMM) Programme.

% of population above 18 years of age for total Saudi population, nationals and expatriates

71% 23,723,699

Population of MDD patientsa 5.10% 1,209,909


Population of TRD patientsb 21.7% 101,709


Population adjusted for suicide related mortalityc

Non-response/ Relapse: 0.47%

Partial Response: 0.24%

101,639


*Assumed to be half of the rate for the Non-response/Relapse health state

Abbreviations: MDD: major depressive disorder; TRD: treatment resistant depressionaPopulation of MDD patients was calculated by applying prevalence rate of MDD (5.10%) on the % of population above age 18 years for total Saudi nationals and expatriatesbPopulation of TRD patients was calculated by applying rate of MDD patients diagnosed, MDD patients treated, treated patients without psychotic features, and then progression rate of MDD to TRD (55.9%, 77.0%, 90.0%, and 21.7%)cPopulation adjusted for suicide related mortality was calculated by applying rate of health state mortality (Non-response/ Relapse: 0.47%; Partial Response: 0.24%) at the end of each patient cycle in the Markov trace

iqvia.com | 27

Table 24: Overall cost burden of TRD by line of therapy

Across different lines of therapy, the economic burden due to combination therapy was estimated to be SAR 853 million (5.7% of the total), while the burden due to augmentation and ECT was SAR 792 million (5.3%) and 12,378 million (82.5%), respectively. Table 26 presents the overall costs by treatment, outpatient physician visit, hospitalization, monitoring, adverse event, and psychological/behavioral treatment. The total number of patients at the end of the time horizon was reported to be 101,639 after adjustment for suicide-related mortality.

Table 25 presents the breakdown of the overall cost burden by health state. The highest cost was incurred due to the non-response state (SAR 6,872 million, 45.8% of the total), followed by the partial response state (SAR 2,361 million, 15.7%) and remission (SAR 2,075 million, 13.8%). The cost associated with ECT was the major driving factor among various health states as presented in Figure 5. The cost per patient based on the number of patients for the entire time horizon was SAR 2.2 million. Table 27 presents the cost breakdown per patient.

Figure 4: Cost breakdown by health state

TOTAL COSTS NUMBER OF PATIENTS AT THE END OF TIME HORIZON

Antidepressant 1* SAR 485,161,190 0

Antidepressant 2** SAR 488,699,210 0

Combination SAR 853,190,923 4,960

Augmentation*** SAR 791,792,947 4,640

ECT SAR 12,378,332,841 92,039

Total SAR 14,997,177,111 101,639

Abbreviation: ECT: Electroconvulsive therapy; SAR: Saudi Riyal*Antidepressant 1 consists of SSRI’s**Antidepressant 2 consists of SNRI’s***Augmentation consists of various antipsychotics and anti-convulsant

Partial Response17%

Non-response49%

Remission15%

Recovery12%

Relapse7%


Figure 5: Cost bifurcation per health state

Table 25: Overall cost breakdown by health state

68 64

2,228

283 277

6,312

279 234

1,562

191 191

1,254

32 23

1,021

0

1,000

2,000

3,000

4,000

5,000

6,000

7,000

Partial Response Non-response Remission Recovery Relapse

valu

es (i

n M

illion

s)

Combination/Augmentation ECTAugmentation***

PARTIAL RESPONSE

NON-RESPONSE REMISSION RECOVERY RELAPSE TOTAL

Antidepressant 1*

SAR 485,161,190

Antidepressant 2**

SAR 488,699,210

Combination/ Augmentation

SAR 68,374,469

SAR 282,807,886

SAR 278,838,915

SAR 191,326,249

SAR 31,843,404

SAR 853,190,923

Augmentation*** SAR 63,945,567

SAR 277,309,202

SAR 233,840,123

SAR 193,314,043

SAR 23,384,012

SAR 791,792,947

ECT SAR 2,228,245,718

SAR 6,312,229,462

SAR 1,562,465,039

SAR 1,254,016,852

SAR 1,021,375,771

SAR 12,378,332,841

Total SAR 2,360,565,754

SAR 6,872,346,549

SAR 2,075,144,077

SAR 1,638,657,144

SAR 1,076,603,187

SAR 14,997,177,111


iqvia.com | 29

Table 26: Overall costs by service provided

Table 27: Cost breakdown per patient (per intervention for entire time horizon)

COST# COMPONENT

ANTIDEPRES-SANT 1*

ANTIDEPRES-SANT 2**

COMBINA-TION/ AUG-MENTATION

AUGMENTA-TION *** ECT TOTAL

Treatment cost SAR 5,526,603 SAR 8,067,452 SAR 23,648,878

SAR 20,235,449

SAR 1,400,859,633

SAR 1,458,338,015

Outpatient physician visit cost

SAR 30,512,557

SAR 30,512,557

SAR 53,081,124

SAR 39,912,655

SAR 303,430,621

SAR 457,449,514

Hospitalization costs - SAR

4,562,264,431SAR

4,562,264,431

Productivity Loss SAR 147,809,866

SAR 700,290,328

SAR 848,100,194

Adverse event cost

SAR 353,742,245

SAR 353,742,245

SAR 615,387,165

SAR 462,720,714

SAR 4,482,365,382

SAR 6,267,957,751

Psychological and behavioural treatment

SAR 2,789,956 SAR 3,787,127 SAR - SAR - SAR 8,367,459 SAR 14,944,542

Total SAR 92,589,828

SAR 92,589,828

SAR 161,073,756

SAR 121,114,264

SAR 920,754,987

SAR 1,388,122,664


COST# COMPONENT

ANTIDEPRES-SANT 1*

ANTIDEPRES-SANT 2**



Treatment cost SAR 54 SAR 79 SAR 2,139 SAR 2,586 SAR 231,666 SAR 236,523


SAR 300 SAR 300 SAR 4,800 SAR 5,100 SAR 50,400 SAR 60,900

Hospitalization costs SAR - SAR - SAR - SAR - SAR 757,795 SAR 757,795

Monitoring cost SAR - SAR - SAR - SAR 18,887 SAR 86,658 SAR 105,545

Productivity Loss SAR 3,478 SAR 3,478 SAR 55,648 SAR 59,126 SAR 744,523 SAR 866,253

Adverse event cost SAR 27 SAR 37 SAR - SAR - SAR 1,750 SAR 1,815

Psychological and behavioural Treatment

SAR 95 SAR 910 SAR 14,566 SAR 15,476 SAR 152,938 SAR 184,800

Total SAR 4,770 SAR 4,805 SAR 77,152 SAR 101,175 SAR 2,025,730 SAR 2,213,631

Abbreviation: ECT: Electroconvulsive therapy; SAR: Saudi Riyal*Antidepressant 1 consists of SSRI’s**Antidepressant 2 consists of SNRI’s***Augmentation consists various antipsychotics and anti-convulsant


3.1.2. SCENARIO ANALYSIS3.1.2.1. Scenario 1 analysisThe scenario 1 analysis includes only Saudi adult (≥18 years age) nationals with the “TRD” burden.

The model estimated that, at the end of the 1-year time horizon, KSA would have 56,946 TRD patients, with an overall economic burden of SAR 8,171 million. Table 28 provides a summary of the population estimates, including the total Saudi national population, total MDD population and total TRD population for Scenario 1 in KSA.

Table 28: Population estimates in Scenario 1


Total Saudi population, expatriate and nationals 33,413,660


Total Saudi nationals 20,768,627

% of population above 18 years of age for total Saudi nationals 64% 13,291,921

Population of MDD patientsa 5.10% 677,888


MDD patients progressed to TRDb 21.7% 56,985



Non-response/ Relapse: 0.47% 56,946



Abbreviations: MDD: major depressive disorder; TRD: treatment resistant depressionaPopulation of MDD patients was calculated by applying the prevalence rate of MDD (5.10%) on the % of population above age 18 years for total Saudi nationals.bMDD patients progressed to TRD was calculated by applying the rate of MDD patients diagnosed, MDD patients treated, treated population without psychotic features, and progression rate of MDD to TRD (55.9%, 77.0%, 90.0%, and 21.7%)cPopulation adjusted for suicide related mortality was calculated by applying the rate of health state mortality (Non-response/ Relapse: 0.47%; Partial Response: 0.24%) at the end of each patient cycle in the Markov trace.

iqvia.com | 31

The major driving factor of the burden of disease was productivity loss (SAR 3,511 million, 42.0%), followed by hospitalization cost (SAR 2,556 million, 30.3%). Appendix Table 2 presents the breakdown of overall cost burden by health state. Appendix Table 3 presents the overall costs in an aggregated and disaggregated manner (by treatment, outpatient physician visit, hospitalization, monitoring, adverse event, and psychological/behavioral treatment).

Table 29: Overall cost burden of TRD by line of therapy in Scenario 1

SCENARIO 1

Antidepressant 1* SAR 271,826,264

Antidepressant 2** SAR 273,808,546


Augmentation *** SAR 443,626,001 2,600

ECT SAR 6,935,336,200 51,567

Total SAR 8,402,623,088 56,946



3.1.2.2. Scenario 2 analysisThe scenario 2 analysis includes the total Saudi adult (≥18 years age) population (including nationals and expatriates) with “Entire MDD including TRD”.

The model estimated that, at the end of the time horizon, KSA will have 468,633 MDD patients, with an overall economic burden of SAR 37,949 million over a period of 1 year. Table 30 provides a summary of the population estimates, including total Saudi adult population (nationals and expatriates), total MDD population and total TRD population for Scenario 2 in KSA.



Total Saudi population, nationals and expatriates 33,413,660 General Authority for Statistics (GaStat),


% of population above 18 years of age for total population, nationals and expatriates

71% 23,723,699

Population of MDD patientsa 5.10% 1,209,909

Kessler RC, Samps on NA, Berglund P, et al. Anxious and non-anxious major depressive disorder in the World Health Organization World Mental Health Surveys. 2015;24(3):210-2268.

Population of MDD without Psychotic Features (treated and diagnosedb

90.0% 468,703 HCP Quantitative Report –Capacity Assessment in KSA

Population of MDD adjusted for suicide related mortalityc



468,633



Abbreviations: MDD: major depressive disorder; TRD: treatment resistant depressionaPopulation of MDD patients was calculated by applying prevalence rate of MDD (5.10%) on the % of population above age 18 years for total Saudi nationals and expatriatesbPopulation of MDD without Psychotic Features (treated and diagnosed) was calculated by applying rate of MDD patients diagnosed, treated, and population without psychotic features (55.9%, 77.0%, and 90.0%) on the population of MDD patientscPopulation adjusted for suicide related mortality was calculated by applying rate of health state mortality (Non-response/ Relapse: 0.47%; Partial Response: 0.24%) at the end of each patient cycle in the Markov trace

iqvia.com | 33

The total burden of the MDD population was 150% larger than the total burden of the MDD-TRD population (SAR 3,795 million versus SAR 1,499 million). The major driving factor of the burden of disease was productivity loss burden (SAR 860,672 million, 41.0%), followed by hospitalization cost (SAR 680,960 million, 32.5%). Appendix Table 4 presents the breakdown of overall cost burden by health state. Appendix Table 5 presents the overall costs in an aggregated and disaggregated manner (by treatment, outpatient physician visit, hospitalization, monitoring, productivity loss burden, adverse event, and psychological/behavioral treatment).

The total number of patients at the end of the time horizon in scenario 2 was reported to be 468,633.


SCENARIO 2

Total costs Number of patients at the end of time horizon

Antidepressant 1* SAR 8,723,595,986 112,871

Antidepressant 2** SAR 15,202,175,952 254,123


Augmentation *** SAR 791,792,947 4,640

ECT SAR 12,378,332,841 92,039

Total SAR 37,949,088,649 468,633



3.2. KUWAIT3.2.1. Base CaseIn this base case, the model estimated that, at the end of the time horizon of 1 year, Kuwait would have 13,549 TRD patients, presenting an overall economic burden of KWD 304 million. Table 32 provides a summary of the population estimates including total Kuwait adult population (nationals and expatriates), total MDD population and total TRD population for the base case for Kuwait.



Total Kuwati population, nationals and expatriates 4,621,638 General Authority for Statistics (GaStat),


% of population above 16 years of age for total Kuwati population, nationals and expatriates

80% 3,697,310








13,549



Abbreviations: MDD: major depressive disorder; TRD: treatment resistant depressionaPopulation of MDD patients was calculated by applying prevalence rate of MDD (5.10%) on the % of population above age 18 years for total Saudi nationals and expatriatesbPopulation of TRD patients was calculated by applying rate of MDD patients diagnosed, MDD patients treated, treated patients without psychotic features, and then progression rate of MDD to TRD (55.9%, 77.0%, 90.0%, and 21.7%)cPopulation adjusted for suicide related mortality was calculated by applying rate of health state mortality (Non-response/ Relapse: 0.47%; Partial Response: 0.24%) at the end of each patient cycle in the Markov trace

iqvia.com | 35

The major driving factor of the burden of disease was the treatment cost (KWD 178 million, 58.6%), followed by productivity loss (KWD 96 million, 31.6%).


Across different lines of therapy, the economic burden due to combination therapy was estimated to be KWD 12 million (3.9% of the total), while the burden due to augmentation and ECT was KWD 10 million (3.3%) and KWD 268 million (88.2%) respectively. Table 35 presents the overall costs by treatment, outpatient physician visit, hospitalization, monitoring, productivity loss burden, adverse events, and psychological/behavioral treatment. The total number of patients at the end of the time horizon was reported to be 13,549 after adjustment for suicide-related mortality.

Table 34 presents the breakdown of the overall cost burden by health state. The highest cost was incurred due to the non-response state (KWD 144 million, 47.4% of the total), followed by the partial response state (KWD 50 million, 16.5%) and remission (KWD 41 million, 13.5%). The cost associated with ECT is the major driving factor among various health states as presented in Figure 7.

SCENARIO 2

Antidepressant 1* KWD 6,915,729 0

Antidepressant 2** KWD 6,930,753 0

Combination KWD 12,343,675 661

Augmentation*** KWD 9,703,153 619

ECT KWD 268,095,264 12,269

Total KWD 303,988,575 13,549

Abbreviation: ECT: Electroconvulsive therapy; KWD: Kuwaiti Dinar*Antidepressant 1 consists of SSRI’s**Antidepressant 2 consists of SNRI’s***Augmentation consists of various antipsychotics and anti-convulsant


The cost per patient based on the number of the patients for the entire time horizon was KWD 4 million. Table 36 presents the cost breakdown per patient.

Figure 6: Cost breakdown by health state

Figure 7: Cost bifurcation per health state

Partial Response17%

Non-response50%

Remission14%

Recovery11%

Relapse8%

1 1

48

4 3

137

4 3

34

3 2

27

0 0

22


valu

es (i

n M

illion

s)


0

20

40

60

80

100

120

140

160

iqvia.com | 37



COST# COMPONENT

ANTIDEPRES-SANT 1*

ANTIDEPRES-SANT 2**



Antidepressant 1* KWD 6,915,729

Antidepressant 2** KWD 6,930,753

Combination/ Augmentation KWD 989,218 KWD

4,091,568KWD

4,034,146KWD

2,768,043 KWD 460,700 KWD 12,343,675

Augmentation*** KWD 783,631 KWD 3,398,330

KWD 2,865,631

KWD 2,368,998 KWD 286,563 KWD 9,703,153

ECT KWD 48,260,310

KWD 136,712,997

KWD 33,798,933

KWD 27,134,682

KWD 22,188,343

KWD 268,095,264

Total KWD 50,033,159

KWD 144,202,895

KWD 40,698,710

KWD 32,271,723

KWD 22,935,606

KWD 303,988,575

Abbreviation: ECT: Electroconvulsive therapy; KWD: Kuwaiti Dinar*Antidepressant 1 consists of SSRI’s**Antidepressant 2 consists of SNRI’s***Augmentation consists of various antipsychotics and anti-convulsant

COST# COMPONENT

ANTIDEPRES-SANT 1*

ANTIDEPRES-SANT 2**



Treatment cost KWD 181,100 KWD 191,818 KWD 648,746 KWD 909,525 KWD 175,587,749

KWD 177,518,938


KWD 271,162 KWD 271,162 KWD 471,727 KWD 354,700 KWD 2,696,557 KWD 4,065,308

Hospitalization costs KWD - KWD - KWD - KWD - KWD

10,860,103KWD

10,860,103

Monitoring cost KWD - KWD - KWD - KWD - KWD - KWD -

Productivity loss burden

KWD 5,412,485

KWD 5,412,485

KWD 9,415,821

KWD 7,079,926

KWD 68,583,085

KWD 95,903,801

Adverse event cost KWD 12,048 KWD 16,354 - - KWD 36,132 KWD 64,533


KWD 1,038,935

KWD 1,038,935

KWD 1,807,382

KWD 1,359,003

KWD 10,331,637

KWD 15,575,892

Total KWD 6,915,729

KWD 6,930,753

KWD 12,343,675

KWD 9,703,153

KWD 268,095,264

KWD 303,988,575

Abbreviation: ECT: Electroconvulsive therapyKWD: Kuwaiti Dinar*Antidepressant 1 consists of SSRI’s**Antidepressant 2 consists of SNRI’s***Augmentation consists various antipsychotics and anti-convulsant# Kuwaiti Dinar



COST# COMPONENT

ANTIDEPRES-SANT 1*

ANTIDEPRES-SANT 2**



Treatment cost KWD 13 KWD 14 KWD 440 KWD 872 KWD 218,024 KWD 219,364


KWD 20 KWD 20 KWD 320 KWD 340 KWD 3,360 KWD 4,060

Hospitalization costs KWD - KWD - KWD - KWD - KWD 13,532 KWD 13,532


Productivity loss burden KWD 399 KWD 399 KWD 6,387 KWD 6,787 KWD 85,457 KWD 99,429

Adverse event cost KWD 1 KWD 1 KWD - KWD - KWD 57 KWD 59


KWD 77 KWD 77 KWD 1,226 KWD 1,303 KWD 12,874 KWD 15,556

Total KWD 510 KWD 511 KWD 8,373 KWD 9,301 KWD 333,303 KWD 351,999


iqvia.com | 39

3.2.2. SCENARIO ANALYSIS3.2.2.1. Scenario 1 analysisScenario 1 analysis consists of Kuwaiti adult (≥16 years of age) nationals with the “TRD” burden.

The model estimated that, at the end of the 1-year time horizon, Kuwait would have 3,239 patients with TRD with an overall economic burden of KWD 72 million. Table 37 provides a summary of the population estimates, including the total Kuwaiti national population, total MDD population and total TRD population for Scenario 1 in Kuwait.


The major driving factor of the burden of disease was treatment cost (KWD 42 million 58%), followed by productivity loss (KWD 22 million, 32%). Appendix Table 6 presents the breakdown of overall cost burden by health state. Appendix Table 7 presents overall costs in an aggregated and disaggregated manner (by treatment, outpatient physician visit, hospitalization, monitoring, adverse event, and psychological/behavioral treatment).


Total Kuwati population, expatriate and nationals 46,21,638


Total Kuwati nationals 14,03,113

% of population above 16 years of age for total Kuwati nationals 63% 883,961



MDD patients progressed to TRDb 21.7% 3242





3239



Abbreviations: MDD: major depressive disorder; TRD: treatment resistant depressiona Population of MDD patients was calculated by applying prevalence rate of MDD (5.10%) on the % of population above age 18 years for total Saudi nationals.

b MDD patients progressed to TRD was calculated by applying rate of MDD patients diagnosed, MDD patients treated, treated population without psychotic features, and progression rate of MDD to TRD (55.9%, 77.0%, 90.0%, and 21.7%)

c Population adjusted for suicide related mortality was calculated by applying rate of health state mortality (Non-response/ Relapse: 0.47%; Partial Response: 0.24%) at the end of each patient cycle in the Markov trace.



3.2.2.2. Scenario 2 analysisThe scenario 2 analysis includes the Kuwaiti total adult (≥16 years of age) population (including nationals and expatriates) with “Entire MDD including TRD”.

The model estimated that, at the end of the time horizon, Kuwait would have 62,470 MDD patients, with an overall economic burden of KWD 629 million over a period of 1 year. Table 39 provides a summary of the population estimates, including the total Kuwaiti adult population (nationals and expatriates), total MDD population and total TRD population for Scenario 2 in Kuwait.


SCENARIO 1




Combination/ Augmentation KWD 2,951,153 158

Augmentation *** KWD 2,319,851 148

ECT KWD 64,096,812 2,933

Total KWD 72,678,264 3,239


Total Kuwait population, nationals and expatriates 4,621,638 General Authority for Statistics (GaStat),


% of population above 16 years of age for total population, nationals and expatriates

80% 3,697,310




85.0% 62,480 HCP Quantitative Report –Capacity Assessment in Kuwait




62,470



Abbreviations: MDD: major depressive disorder; TRD: treatment resistant depressionaPopulation of MDD patients was calculated by applying prevalence rate of MDD (5.10%) on the % of population above age 18 years for total Saudi nationals and expatriatesbPopulation of MDD without Psychotic Features (treated and diagnosed) was calculated by applying rate of MDD patients diagnosed, treated, and population without psychotic features (55.9%, 77.0%, and 90.0%) on the population of MDD patients.cPopulation adjusted for suicide related mortality was calculated by applying rate of health state mortality (Non-response/ Relapse: 0.47%; Partial Response: 0.24%) at the end of each patient cycle in the Markov trace.

iqvia.com | 41

The major driving factor of the burden of disease was productivity loss (KWD 364 million 56.0%), followed by treatment cost (KWD 186 million, 29%). Appendix Table 8 presents the breakdown of overall cost burden by health state. Appendix Table 9 presents overall costs in an aggregated and disaggregated manner (by treatment, outpatient physician visit, hospitalization, monitoring, adverse event, and psychological/behavioral treatment).



SCENARIO 1


Antidepressant 1* KWD 124,350,484 15,046

Antidepressant 2** KWD 215,183,121 33,875

Combination KWD 12,343,675 661

Augmentation *** KWD 9,703,153 619

ECT KWD 268,095,264 12,269

Total KWD 629,675,698 62,470

Abbreviation: ECT: Electroconvulsive therapy; KWD: Kuwaiti Dinar*Antidepressant 1 consists of SSRI’s**Antidepressant 2 consists of SNRI’s***Augmentation consists various antipsychotics and anti-convulsant


3.3. UAE3.3.1. Base CaseIn this base case, the model estimated that, at the end of the time horizon of 1 year, UAE would have 32,412 TRD patients, presenting an overall economic burden of AED 2,461 million. Table 41 provides a summary of the population estimates, including the total UAE adult population (nationals and expatriates), total MDD population and total TRD population for the base case for UAE.



Total UAE population, nationals and expatriates 9,540,000 General Authority for Statistics (GaStat),

Demographic Survey 2017; Gulf Labour Markets, Migration and Population (GLMM) Programme

% of population above 19 years of age for total UAE population, nationals and expatriates

78% 7,441,200


Kessler RC, Sampson NA, Berglund P, et al. Anxious and non-anxious major depressive disorder in the World Health Organization World Mental Health Surveys. 2015;24(3):210-2268






32,412



Abbreviations: MDD: major depressive disorder; TRD: treatment resistant depressiona Population of MDD patients was calculated by applying prevalence rate of MDD (5.10%) on the % of population above age 18 years for total Saudi nationals and expatriates

b Population of TRD patients was calculated by applying rate of MDD patients diagnosed, MDD patients treated, treated patients without psychotic features, and then progression rate of MDD to TRD (55.9%, 77.0%, 90.0%, and 21.7%).


iqvia.com | 43

TOTAL COSTS NUMBER OF PATIENTS AT THE END OF TIME HORIZON

Antidepressant 1* AED 115,663,267 0

Antidepressant 2** AED 113,553,941 0

Combination/ Augmentation AED 211,744,861 1,582

Augmentation *** AED 168,347,587 1,480

ECT AED 1,851,823,752 29,350

Total AED 2,461,133,408 32,412

Abbreviation: ECT: Electroconvulsive therapy; AED: Emirati dirham*Antidepressant 1 consists of SSRI’s**Antidepressant 2 consists of SNRI’s***Augmentation consists various antipsychotics and anti-convulsant

Table 42 presents the overall burden and breakdown in terms of cost and number of patients at the end of the time horizon. The major driving factor of the burden of disease was productivity loss (AED 1,057,024,023, 42.9%), followed by outpatient physician visit cost (AED 486,255,098, 20%)


Across different lines of therapy, the economic burden due to combination therapy was estimated to be AED 212 million (9% of the total), while that due to augmentation and ECT was 168 million (7%) and AED 1,852 million (75%), respectively. Table 44 presents the overall costs by treatment, outpatient physician visit, hospitalization, monitoring, productivity loss, adverse event, and psychological/behavioral treatment. The total number of patients at the end of the time horizon was reported to be 32,412 after adjustment for suicide related mortality.

Table 43 presents the breakdown of overall cost burden by health state. The highest cost was incurred due to the non-response state (AED 1,073 million, 44% of the total), followed by partial response state (AED 364 million 15%) and remission (AED 353 million, 14%). The cost associated with ECT is the major driving factor among various health states as presented in Figure 9.


The cost per patient based on the number of the patients for the entire time horizon was AED 975,686. Table 45 presents the cost breakdown per patient.

Figure 8: Coast Breakdown by health state

Figure 9: Cost bifurcation of health state

Partial Response16%

Non-response48%

Remission16%

Recovery12%

Relapse8%

17 14

333

70 59

944

69 50

234

47 41

188

8 5

153

0100200300400500

700800900

600

1000


valu

es (i

n M

illion

s)


iqvia.com | 45



PARTIAL RESPONSE

NON- RESPONSE REMISSION RECOVERY RELAPSE TOTAL

Antidepressant 1*

AED 115,663,267

Antidepressant 2**

AED 113,553,941

Combination/ Augmentation

AED 16,969,171

AED 70,187,240

AED 69,202,221

AED 47,483,334 AED 7,902,894 AED

211,744,861

Augmentation ***

AED 13,595,830

AED 58,960,282

AED 49,718,074

AED 41,101,595 AED 4,971,807 AED

168,347,587

ECT AED 333,350,096

AED 944,322,378

AED 233,661,266

AED 187,577,861

AED 152,912,152

AED 1,851,823,752

Total AED 363,915,096

AED 1,073,469,900

AED 352,581,562

AED 276,162,790

AED 165,786,853

AED 2,461,133,408


COST# COMPO-NENT

ANTIDEPRES-SANT 1*

ANTIDEPRES-SANT 2**



Treatment cost AED 8,450,562 AED 6,265,545 AED 25,600,853

AED 28,382,549

AED 365,010,831

AED 433,710,341


AED 32,433,932

AED 32,433,932

AED 56,423,641

AED 42,425,954

AED 322,537,639

AED 486,255,098

Hospitalization costs AED - AED - AED - AED - AED

259,444,003AED

259,444,003

Monitoring cost AED - AED - AED - AED - AED - AED -

Productivity loss burden

AED 59,654,845

AED 59,654,845

AED 103,778,462

AED 78,032,898

AED 755,902,971

AED 1,057,024,023

Adverse event cost AED 211,775 AED 287,466 - - AED 635,141 AED 1,134,381


AED 14,912,153

AED 14,912,153

AED 25,941,904

AED 19,506,186

AED 148,293,167

AED 223,565,562

Total AED 115,663,267

AED 113,553,941

AED 211,744,861

AED 168,347,587

AED 1,849,970,275

AED 2,461,133,408




COST# COMPO-NENT

ANTIDEPRES-SANT 1*

ANTIDEPRES-SANT 2**



Treatment cost AED 261 AED 193 AED 7,260 AED 11,373 AED 181,856 AED 200,942


AED 1,000 AED 1,000 AED 16,000 AED 17,000 AED 168,000 AED 203,000

Hospitalization costs AED - AED - AED - AED - AED 135,136 AED 135,136

Monitoring cost AED - AED - AED - AED - AED - AED -

Productivity loss burden AED 1,839 AED 1,839 AED 29,428 AED 31,268 AED 393,727 AED 458,101

Adverse event cost AED 7 AED 9 AED - AED - AED 417 AED 432


AED 460 AED 460 AED 7,356 AED 7,816 AED 77,241 AED 93,333

Total AED 3,566 AED 3,501 AED 60,044 AED 67,457 AED 956,377 AED 1,090,945

Abbreviation: ECT: Electroconvulsive therapy; AED: Emirati dirham*Antidepressant 1 consists of SSRI’s**Antidepressant 2 consists of SNRI’s***Augmentation consists various antipsychotics and anti-convulsant#in AED

iqvia.com | 47

3.3.2. SCENARIO ANALYSIS3.3.2.1. Scenario 1 analysisThe scenario 1 analysis includes only UAE adult (≥19 years of age) nationals with the “TRD” burden

The model estimated that, at the end of the 1-year time horizon, UAE would have 3,727 TRD patients with an overall economic burden of AED 283 Million. Table 46 provides a summary of the population estimates, including the total UAE national population, total MDD population and total TRD population for Scenario 1 in UAE.


The major driving factor of the burden of disease was productivity loss (AED 121 million, 43%), followed by outpatient physician visit cost (AED 55 million, 20%). Appendix Table 10 presents the breakdown of overall cost burden by health state. Appendix Table 11 presents overall costs in an aggregated and disaggregated manner (by treatment, outpatient physician visit, hospitalization, monitoring, adverse event, and psychological/behavioral treatment).


Total UAE population, expatriate and nationals 9,540,000


Total UAE nationals 1,097,100

% of population above 19 years of age for total Saudi nationals 78% 855,738


Kessler RC, Sampson NA, Berglund P, et al. Anxious and non-anxious major depressive disorder in the World Health Organization World Mental Health Surveys. 2015;24(3):210-2268

MDD patients progressed to TRDb 21.7% 3,730





3,727



Abbreviations: MDD: major depressive disorder; TRD: treatment resistant depressiona Population of MDD patients was calculated by applying prevalence rate of MDD (5.10%) on the % of population above age 18 years for total Saudi nationals.

b MDD patients progressed to TRD was calculated by applying rate of MDD patients diagnosed, MDD patients treated, treated population without psychotic features, and progression rate of MDD to TRD (55.9%, 77.0%, 90.0%, and 21.7%)




3.3.2.2. Scenario 2 analysisThe scenario 2 analysis includes the total Emirati adult (≥19 years of age) population (including nationals and expatriates) with “Entire MDD including TRD”.

The model estimated that, at the end of the time horizon, the UAE would have 149,443 MDD patients with an overall economic burden of AED 7,902 million over a period of 1 year. Table 48 provides a summary of the population estimates, including total adult UAE population (nationals and expatriates), total MDD population and total TRD population for Scenario 2 in UAE.


SCENARIO 1


Antidepressant 1* AED 13,301,276 0

Antidepressant 2** AED 13,058,703 0

Combination/ Augmentation AED 24,350,659 182

Augmentation *** AED 19,359,973 170

ECT AED 212,959,731 3,375

Total AED 283,030,342 3,727


Total UAE population, nationals and expatriates 9,540,000 General Authority for Statistics (GaStat),


% of population above 19 years of age for total population nationals and expatriates

78% 7,441,200




95.0% 149,465 HCP Quantitative Report –Capacity Assessment in UAE




149,443



Abbreviations: MDD: major depressive disorder; TRD: treatment resistant depressiona Population of MDD patients was calculated by applying prevalence rate of MDD (5.10%) on the % of population above age 18 years for total Saudi nationals and expatriates

b Population of MDD without Psychotic Features (treated and diagnosed) was calculated by applying rate of MDD patients diagnosed, treated, and population without psychotic features (55.9%, 77.0%, and 90.0%) on the population of MDD patients.


iqvia.com | 49

The major driving factor of the burden of disease was productivity loss (AED 4,015 million, 49.0%), followed by outpatient physician visit cost (AED 2,094 million, 26%). Appendix Table 12 presents the breakdown of the overall cost burden by health state. Appendix Table 13 presents the overall costs in an aggregated and disaggregated manner (by treatment, outpatient physician visit, hospitalization, monitoring, adverse event, and psychological/behavioral treatment).



SCENARIO 2


Antidepressant 1* AED 2,079,720,369 35,994

Antidepressant 2** AED 3,590,607,288 81,038

Combination/ Augmentation AED 211,744,861 1,582

Augmentation *** AED 168,347,587 1,480

ECT AED 1,851,823,752 29,350

Total AED 7,902,243,857 149,443


The overall direct burden of TRD was estimated to be SAR 14,997 million, KWD 304 million and AED 2,461 million over a one-year period, for the KSA, Kuwait and the UAE respectively. This implies that each of the countries will have to spend between 5% and a staggering 20% of their yearly healthcare expenditure (currently SAR 125 billion, KWD 1.5 billion and AED 45 billion, respectively) to combat this disease [29-31]. In these three GCC countries, the productivity loss (i.e. indirect cost) was either the greatest or second greatest component of TRD’s burden, ranging from 32 to 43% of the total.

The direct economic cost aside, another important concern is the negative impact on the quality of life of the patient and those around them. While this is an aspect of any illness, it is of special importance in TRD. While many chronic diseases can be borne by the sufferer with little day-to-day deficiencies, MDD in general (and TRD in particular) is known to negatively impact almost every aspect of an individual’s personal and professional life, resulting in significantly lower QoL scores

Comparable studies in recent published academic literature display a similar trend. While direct comparison between studies is challenging considering the varying methodologies, endpoints and geographies, certain broad conclusions can be drawn from them; in their comprehensive systematic review of literature on the economic and QoL aspects of TRD, Johnston KM et al reported “a clear and consistent trend between increasing level of treatment resistance and increasing total direct medical costs” in no less than five studies,,,,, and a similar association with indirect costs, with costs associated with TRD being up to three times higher than MDD (without TRD). In corroboration, Olchanski N et al20, Gibson T et al and Lepine BA et al also reported increases of 29.3%, 40% and 81.5% for direct costs, respectively, while Ivanova

JI et al reported that both direct and indirect costs for TRD patients were double that of MDD (without TRD) patients.

Depression provides a challenge to any healthcare system simply because of its unusual combination of characteristics: it is a chronic disease (thereby enlarging on both the burden imposed and the expense to treat it) that can involve any gender at any age from adolescence to old age. It shows few outward signs that would allow others to detect it easily (thus defeating many screening modalities) while having a collection of arguably vague (and at times, seeming contradictory) symptoms that the sufferer themselves may not recognize or dismiss. It is not associated with any single definitive diagnostic test and has complicated multi-modality management with agents who themselves have serious (and potential fatal) side effects. Combine all of this with the social stigma that often accompanies the disease, as well as the TRD subtype in which the patient’s treatment options are even more limited as compared to non-treatment resistant depressed patients, and you have the makings of a perfect healthcare storm. The conclusion that can be drawn from the study is that MDD and TRD represent a heavy and growing clinical, economic burden on both individual patients and society as a whole; a burden that would immediately benefit from innovative treatment modalities that would improve its management.

This study has provided a constructive first step towards creating an actionable, effective and economically-sound plan to manage MDD and TRD. More must be done, however, at every functional level and by every stakeholder of the healthcare system. Only by acting in concert can manufacturers, governments, healthcare providers, payers and patients come together to tackle the oncoming “silent tidal wave” of depression and its complications.

4. Discussion and Conclusion

iqvia.com | 51

While the model estimates the clinical and economic burden of TRD, the model does not estimate the negative impact on quality of life. A recent clinical study (TRANSFORM-2) found that people suffering from an episode of MDD have a utility score of just 0.417, highlighting the devastating impact of TRD on health-related quality of life. Secondly, due to the lack of data and studies on the economic burdens associated with undiagnosed and untreated TRD patients, this study did not consider the clinical and economic burden of TRD that is undiagnosed or untreated. The estimates in this study may, therefore, be considered an underestimate of the true clinical and economic burden of MDD and TRD. While the model and the inputs and results were validated by local

KOLs, some uncertainty in the results remains due to a paucity of data. Accounting for all these limitations, decision makers would consider the current findings the minimum economic and clinical burden of MDD and TRD management in KSA, UAE and Kuwait at best. Should more data on the cost and quality of life for the undiagnosed MDD/TRD patients or those with delayed diagnosis become available, the overall burden is expected to be substantially higher than the current estimates.

Despite these limitations, this analysis presents the first attempt to quantify the high clinical and economic burden of TRD management in the GCC from a societal perspective.

5. Limitations


Appendix Table 1: Cost inputs breakdown per class of treatment

6. Appendix

CLASS OF DRUGS

TREATMENT OPTIONS

DOSES(MG)

FRE-QUENCY

NUMBER OF DOSES/

4 WEEKS

UNIT COST

(TENDER PRICE) (IN

SAR)

COST PER

PACK (TENDER

PRICE)(IN SAR)

COST PER

PACK (LIST

PRICE)(IN SAR)

EFFECTIVE COST PER

PACK(IN SAR)

TOTAL COST (IN

SAR)

PROPOR-TION OF

PATIENTS (%) TO BE TREATED

AVER-AGE

COST OF

TREAT-MENT

SSRI

Escitalopram 10 Daily 28 0.2 5.3 52.8 52.8 52.8 67.90%

54.3

Fluoxetine 20 Daily 28 0.1 2.3 91.1 91.1 85 2.40%

Fluvoxamine 50 Daily 28 1.1 31.5 32 32 29.9 2.40%

Paroxetine 25 Daily 28 2.6 76.5 78.3 78.3 73 6.00%

Sertraline 50 Daily 28 NR 128.5 128.5 128.5 119.9 9.50%

SNRI

Venlafaxine 75 Daily 28 0.8 25.1 72.5 72.5 67.7 70.00%

79.3Desvenlafaxine

ER50 Daily 28 3.5 104.9 104.9 104.9 97.9 20.00%

Desvenlafaxine 50 Daily 28 3.5 104.9 132.7 132.7 123.8 10.00%

Anti-maniac Lithium300-

450mgDaily 28 0.4 10.5 10.5 10.5 9.8 50.0% 4.9

Thyroid hormones

Eltroxin50-

100µmcgDaily 28 0.2 6.0 6.0 6.0 5.6 50.0% 2.8

Antipsychotic

Olanzapine 10 Daily 28 0.4 10.5 437.3 437.3 408.1 50.0%124.0

Olanzapine Quetiapine

5 Daily 28 0.2 6.5 266.6 266.6 248.9

300 Daily 28 0.9 27.9 130.9 130.9 122.1 50.0% 61.1

Anti-convulsant therapy

Carbamazepine 200 Daily 28 0.4 13.2 24.0 24.0 22.4 100.0% 22.4

iqvia.com | 53

Appendix Table 2: Overall cost breakdown by health state in Scenario 1

Appendix Table 3: Overall costs in an aggregated and disaggregated manner in Scenario 1

PARTIAL RESPONSE

(SAR)

NON- RESPONSE

(SAR)

REMISSION(SAR)

RECOVERY(SAR)

RELAPSE(SAR)

TOTAL(SAR)

Antidepressant 1* - - - - - 271,826,264

Antidepressant 2** - - - - - 273,808,546

Combination/ Augmentation 38,308,869 158,451,691 156,227,955 107,196,331 17,841,232 478,026,077

Augmentation *** 35,827,443 155,370,886 131,016,017.31 107,160,535 13,101,602 442,476,483

ECT 1,206,889,326 3,418,905,868 875,418,401 735,100,708 468,218,199 6,704,532,501

Total 1,281,025,637 3,732,728,445 1,162,662,373 949,457,573 499,161,033 8,170,669,871

**Antidepressant 2 consists of SNRI’s***Augmentation consists various antipsychotics and anti-convulsant

COST# COMPO-NENT

ANTIDEPRES-SANT 1* (SAR)

ANTIDEPRES-SANT 2**

(SAR)


(SAR)

AUGMEN-TATION ***

(SAR)ECT (SAR) TOTAL

Treatment cost 3,096,447 4,520,035 13,250,001 11,308,146 759,292,751 791,467,379


17,095,585 17,095,585 29,740,309 22,304,330 164,540,275 250,776,084

Hospitalization costs - - - - 2,473,963,385 2,473,963,385

Monitoring cost - - - 82,600,369 372,116,536 454,716,904

Productivity Loss 198,194,816 198,194,816 344,789,313 258,581,533 2,430,636,803 3,430,397,281

Adverse event cost 1,563,158 2,121,853 - - 4,688,122 8,373,133


51,876,258 51,876,258 90,246,454 67,682,105 499,294,629 760,975,704

Total 271,826,264 273,808,546 478,026,077 442,476,483 6,704,532,501 8,170,669,871

Abbreviation: ECT: Electroconvulsive therapy; SAR: Saudi Riyal*Antidepressant 1 consists of SSRI’s**Antidepressant 2 consists of SNRI’s***Augmentation consists various antipsychotics and anti-convulsant#in SAR


Appendix Table 4: Overall cost breakdown by health state in Scenario 2


PARTIAL RESPONSE

(SAR)

NON-RE-SPONSE (SAR)

REMISSION(SAR)

RECOVERY(SAR)

RELAPSE(SAR)

TOTAL(SAR)

Antidepressant 1* 8,723,595,986

Antidepressant 2** 15,104,495,162


Augmentation *** 63,945,567 277,309,202 233,840,122.95 191,262,360 23,384,012 789,741,264

ECT 2,154,081,265 6,102,134,570 1,562,465,039 1,312,023,090 835,685,617 11,966,389,581

Total 2,286,401,301 6,662,251,657 2,075,144,077 1,694,611,699 890,913,033 37,437,412,916


COST# COMPONENT

ANTIDEPRES-SANT 1*

(SAR)

ANTIDEPRES-SANT 2**

(SAR)


(SAR)

AUGMEN-TATION ***

(SAR)

ECT(SAR)

TOTAL(SAR)

Treatment cost 99,372,857 250,957,699 23,648,878 20,183,015 1,355,201,554 1,749,364,002


548,640,794 949,167,202 53,081,124 39,809,234 293,674,919 1,884,373,272

Hospitalization costs - - - - 4,415,581,499 4,415,581,499

Monitoring cost - - - 147,426,863 664,161,361 811,588,224

Productivity Loss 6,360,575,604 11,004,011,757 615,387,165 461,521,718 4,338,251,312 22,779,747,556

Adverse event cost 50,165,703 117,807,786 - - 8,367,459 176,340,947


1,664,841,030 2,880,231,508 161,073,756 120,800,434 891,151,477 5,718,098,205

Total 8,723,595,986 15,202,175,952 853,190,923 789,741,264 11,966,389,581 37,535,093,705

Abbreviation: ECT: Electroconvulsive therapy; SAR: Saudi Riyal*Antidepressant 1 consists of SSRI’s**Antidepressant 2 consists of SNRI’s***Augmentation consists various antipsychotics and anti-convulsant #in SAR

iqvia.com | 55

Appendix Table 6: Breakdown of overall cost burden by health state in Scenario 1


PARTIAL RESPONSE

(SAR)

NON- RESPONSE

(SAR)

REMISSION(SAR)

RECOVERY(SAR)

RELAPSE(SAR)

TOTAL(SAR)



Combination/ Augmentation KWD 236,505 KWD 978,221 KWD 964,493 KWD 661,790 KWD 110,145 KWD 2,951,153

Augmentation *** KWD 187,352 KWD 812,480 KWD 685,121 KWD 566,385 KWD 68,512 KWD 2,319,851

ECT KWD 11,538,182

KWD 32,685,647

KWD 8,080,724

KWD 6,487,420

KWD 5,304,838

KWD 64,096,812


KWD 34,476,349

KWD 9,730,338

KWD 7,715,595

KWD 5,483,496

KWD 72,678,264


COST# COMPO-NENT

ANTIDEPRES-SANT 1* (SAR)

ANTIDEPRES-SANT 2**

(KWD)


(KWD)

AUGMEN-TATION ***

(KWD)ECT (KWD) TOTAL

Treatment cost KWD 43,298 KWD 45,860 KWD 155,104 KWD 217,451 KWD 41,979,909

KWD 42,441,622


KWD 64,830 KWD 64,830 KWD 112,781 KWD 84,802 KWD 644,699 KWD 971,943


2,596,458 KWD 2,596,458


Productivity Loss KWD 1,294,029

KWD 1,294,029 KWD 2,251,155 KWD

1,692,684KWD

16,396,996KWD

22,928,894

Adverse event cost KWD 2,880 KWD 3,910 KWD - KWD - KWD 8,639 KWD 15,429


KWD 248,391 KWD 248,391 KWD 432,113 KWD 324,913 KWD 2,470,111 KWD 3,723,919

Total KWD 1,653,428 KWD 1,657,020 KWD 2,951,153 KWD

2,319,851KWD

64,096,812KWD

72,678,264

Abbreviation: ECT: Electroconvulsive therapy; KWD: Kuwaiti Dinar*Antidepressant 1 consists of SSRI’s**Antidepressant 2 consists of SNRI’s***Augmentation consists various antipsychotics and anti-convulsant#in SAR




PARTIAL RESPONSE

(KWD)

NON-RE-SPONSE (KWD)

REMISSION(KWD)

RECOVERY(KWD)

RELAPSE(KWD

TOTAL(KWD)

Antidepressant 1*

KWD 124,350,484

Antidepressant 2**

KWD 215,183,121

Combination/ Augmentation KWD 989,218 KWD

4,091,568KWD

4,034,146KWD

2,768,043 KWD 460,700 KWD 12,343,675

Augmentation *** KWD 783,631 KWD

3,398,330KWD

2,865,631KWD

2,368,998 KWD 286,563 KWD 9,703,153

ECT KWD 48,260,310

KWD 136,712,997

KWD 33,798,933

KWD 27,134,682

KWD 22,188,343

KWD 268,095,264


KWD 144,202,895

KWD 40,698,710

KWD 32,271,723

KWD 22,935,606

KWD 629,675,698


COST# COMPONENT

ANTIDEPRES-SANT 1*(KWD)

ANTIDEPRES-SANT 2**

(KWD)


(KWD)

AUGMEN-TATION ***

(KWD)

ECT(KWD)

TOTAL(KWD)

Treatment cost KWD 3,256,327

KWD 6,446,222 KWD 648,746 KWD 909,525 KWD

175,587,749KWD

186,848,568


KWD 4,875,715 KWD 9,112,663 KWD 471,727 KWD 354,700 KWD

2,696,557KWD

17,511,362


10,860,103KWD

10,860,103


Productivity Loss KWD 97,320,914

KWD 181,891,806

KWD 9,415,821

KWD 7,079,926

KWD 68,583,085

KWD 364,291,552

Adverse event cost KWD 216,625 KWD 549,577 KWD - KWD - KWD 36,132 KWD 802,335


KWD 18,680,902

KWD 34,914,417

KWD 1,807,382

KWD 1,359,003

KWD 10,331,637

KWD 67,093,341

Total KWD 124,350,484

KWD 232,914,685

KWD 12,343,675

KWD 9,703,153

KWD 268,095,264

KWD 647,407,261

iqvia.com | 57



PARTIAL RESPONSE

(AED)

NON-RE-SPONSE (AED)

REMISSION(AED)

RECOVERY(AED)

RELAPSE(AED)

TOTAL(AED)

Antidepressant 1* 13,301,276

Antidepressant 2** 13,058,703

Combination/ Augmentation 1,951,455 8,071,533 7,958,255 5,460,583 908,833 24,350,659

Augmentation *** 1,563,520 6,780,432 5,717,579 4,726,683 571,758 19,359,973

ECT 38,335,261 108,597,073 26,871,046 21,571,454 17,584,897 212,959,731

Total 41,850,236 123,449,038 40,546,880 31,758,721 19,065,488 283,030,342


COST# COMPONENT

ANTIDEPRES-SANT 1* (AED)

ANTIDEPRES-SANT 2**

(AED)


(AED)

AUGMEN-TATION ***

(AED)ECT (AED) TOTAL

Treatment cost 971,815 720,538 2,944,098 3,263,993 41,976,246 49,876,689


3,729,902 3,729,902 6,488,719 4,878,985 37,091,828 55,919,336

Hospitalization costs - - - - 29,836,060 29,836,060

Monitoring cost - - - - - -

Productivity Loss 6,860,307 6,860,307 11,934,523 8,973,783 86,928,842 121,557,763

Adverse event cost 24,354 33,059 - - 73,041 130,454


1,714,898 1,714,898 2,983,319 2,243,211 17,053,714 25,710,040

Total 13,301,276 13,058,703 24,350,659 19,359,973 212,959,731 283,030,342

Abbreviation: ECT: Electroconvulsive therapy; AED: Emirati dirham*Antidepressant 1 consists of SSRI’s**Antidepressant 2 consists of SNRI’s***Augmentation consists various antipsychotics and anti-convulsant#in AED




PARTIAL RESPONSE

(AED)

NON-RE-SPONSE (AED)

REMISSION(AED)

RECOVERY(AED)

RELAPSE(AED)

TOTAL(AED)

Antidepressant 1* 2,079,720,369

Antidepressant 2** 3,590,607,288


Augmentation *** 13,595,830 58,960,282 49,718,074 41,101,595 4,971,807 168,347,587

ECT 333,350,096 944,322,378 233,661,266 187,577,861 152,912,152 1,851,823,752

Total 363,915,096 1,073,469,900 352,581,562 276,162,790 165,786,853 7,902,243,857

Abbreviation: ECT: Electroconvulsive therapy; AED: Emirati dirham *Antidepressant 1 consists of SSRI’s**Antidepressant 2 consists of SNRI’s***Augmentation consists various antipsychotics and anti-convulsant

COST# COMPONENT

ANTIDEPRES-SANT 1*

(AED)

ANTIDEPRES-SANT 2**

(AED)


(AED)

AUGMEN-TATION ***

(AED)

ECT(AED)

TOTAL(AED)

Treatment cost 151,948,035 210,559,720 25,600,853 28,382,549 365,010,831 781,501,990


583,188,690 1,089,973,771 56,423,641 42,425,954 322,537,639 2,094,549,695

Hospitalization costs - - - - 259,444,003 259,444,003

Monitoring cost - - - - - -

Productivity Loss 1,072,643,033 2,004,758,992 103,778,462 78,032,898 755,902,971 4,015,116,357

Adverse event cost 3,807,880 9,660,568 - - 635,141 14,103,589


268,132,731 501,137,366 25,941,904 19,506,186 148,293,167 963,011,354

Total 2,079,720,369 3,816,090,418 211,744,861 168,347,587 1,851,823,752 8,127,726,988

Abbreviation: ECT: Electroconvulsive therapy; AED: Emirati dirham*Antidepressant 1 consists of SSRI’s**Antidepressant 2 consists of SNRI’s***Augmentation consists various antipsychotics and anti-convulsant #in AED


References 1 WHO | Noncommunicable diseases now biggest killers. Who.int. January 2011. doi:/entity/mediacentre/

news/releases/2008/pr14/en/index.html

2 Global health estimates 2014 summary tables: Estimated deaths by cause, sex and WHO Member State 2012. Geneva: World Health Organization; 2014 (http://www.who.int/healthinfo/global_burden_disease/estimates/en/index1.html, accessed 12 October 2014).

3 WHO EMRO | Kuwait | Countries. Who.int. http://www.emro.who.int/countries/kwt/index.html. Published 2018. Accessed July 5, 2019

4 WHO EMRO | United Arab Emirates | Countries. Who.int. http://www.emro.who.int/countries/are/index.html. Published 2018. Accessed July 5, 2019.</

5 Mental health atlas–2011 country profiles. Geneva: World Health Organization; 2011 (http://www.who.int/mental_health/evidence/atlas/profiles/en/, accessed 1 April 2015)

6 Charara R, Forouzanfar M, Naghavi M, et al. The Burden of Mental Disorders in the Eastern Mediterranean Region, 1990-2013. Maulik PK, ed. PLOS ONE. 2017;12(1):e0169575. doi:10.1371/journal.pone.0169575

7 First, We Need To Talk: Mental Healthcare In The MENA Region | eyeforpharma. Eyeforpharma.com. https://social.eyeforpharma.com/column/first-we-need-talk-mental-healthcare-mena-region. Published 2014. Accessed July 5, 2019.

8 Kessler RC, Sampson NA, Berglund P, et al. Anxious and non-anxious major depressive disorder in the World Health Organization World Mental Health Surveys. Epidemiol Psychiatr Sci. 2015;24(3):210-226.

9 Üstün TB, Ayuso-Mateos JL, Chatterji S, Mathers C, Murray CJJTBjop. Global burden of depressive disorders in the year 2000. 2004;184(5):386-92

10 The Prevalence of Depressive Symptoms and Its Socio-Economic Determinants among University Students in Al Ain, UAE https://innovareacademics.in/journal/ijpps/Vol6Issue5/9307.pdf . Accessed July 5, 2019

11 Depression Definition and DSM-5 Diagnostic Criteria. PsyCom.net - Mental Health Treatment Resource Since 1986. https://www.psycom.net/depression-definition-dsm-5-diagnostic-criteria/. Published 2016

12 NIMH » Depression. Nih.gov. https://www.nimh.nih.gov/health/topics/depression/index.shtml. Published February 7, 2019

13 NIMH » Depression. Nih.gov. https://www.nimh.nih.gov/health/topics/depression/index.shtml#part_145399. Published July 5, 2019. Accessed July 5, 2019.</

14 Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR* D: implications for clinical practice. 2006;163(1):28-40.

15 Souery D, Papakostas GI, Trivedi MHJTJocp. Treatment-resistant depression. 2006;67:16-22

16 Greenberg PE, Kessler RC, Birnbaum HG, Leong SA, Lowe SW, Berglund PA, et al. The economic burden of depression in the United States: how did it change between 1990 and 2000? 2003;64(12):1465-75.


17 European Medicines Agency (2013). Guideline on clinical investigation of medicinal products in the treatment of depression EMA/CHMP/185423/2010 Rev 2. Accessed on 6/19/2019 from https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-clinical-investigation-medicinal-products-treatment-depression_en.pdf.

18 Emerging Therapeutic Approaches to Treatment-Resistant Depression: Meeting Unmet Clinical Needs. American Health & Drug Benefits. http://www.ahdbonline.com/supplements/2684-emerging-therapeutic-approaches-to-treatment-resistant-depression-meeting-unmet-clinical-needs. Published July 12, 2019. Accessed July 05, 2019.

19 Young AS, Klap R, Shoai R, Wells KBJPS. Persistent depression and anxiety in the United States: prevalence and quality of care. 2008;59(12):1391-1398

20 Olchanski N, McInnis Myers M, Halseth M, et al. The economic burden of treatment-resistant depression. Clinical therapeutics. 2013;35(4):512-522

21 Komorowski M, Raffa J. Markov Models and Cost Effectiveness Analysis: Applications in Medical Research. Secondary Analysis of Electronic Health Records. 2016:351-367. doi:10.1007/978-3-319-43742-2_24

22 Sonnenberg F, Beck J. At National Institutes of Health Library On.; 2009. http://www.med.mcgill.ca/epidemiology/courses/EPIB654/Summer2010/Modeling/Markov%20modles%20in%20med%20dec%20making.pdf. Accessed June 26, 2019

23 NIMH » Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study. Nih.gov. https://www.nimh.nih.gov/funding/clinical-research/practical/stard/index.shtml. Published July 5, 2019. Accessed July 5, 2019.</

24 Lavori PW, Rush AJ, Wisniewski SR, et al. Strengthening clinical effectiveness trials: equipoise-stratified randomization. Biol Psychiatry.2001;50(10):792– 801.

25 Al-Harbi KS. Treatment-resistant depression: therapeutic trends, challenges, and future directions. Patient preference and adherence. 2012;6:369.

26 Electroconvulsive therapy (ECT) - Mayo Clinic. Mayoclinic.org. https://www.mayoclinic.org/tests-procedures/electroconvulsive-therapy/about/pac-20393894. Published 2018

27 Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. The American journal of psychiatry. 2006;163(11):1905-17.

28 Relapse or recurrence in depression: why has the cutoff been set at 6 months? - Medicographia. Medicographia. https://www.medicographia.com/2011/10/relapse-or-recurrence-in-depression-why-has-the-cutoff-been-set-at-6-months/. Published October 24, 2011. Accessed July 5, 2019

29 Rizvi SJ, Grima E, Tan M, et al. Treatment-resistant depression in primary care across Canada. 2014;59(7):349-357.

30 Bergfeld IO, Mantione M, Figee M, Schuurman PR, Lok A, Denys DJJoad. Treatment-resistant depression and suicidality. 2018;235:362-367.

31 Hunt IM, Windfuhr K, Swinson N, et al. Electroconvulsive therapy and suicide among the mentally ill in England: a national clinical survey. 2011;187(1-2):145-149.


32 Jakobsen JC, Katakam KK, Schou A, Hellmuth SG, Stallknecht SE, Leth-Møller K, et al. Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis. BMC Psychiatry. 2017;17(1):58-.

33 Huang Q, Zhong X, Yun Y, Yu B, Huang Y. Efficacy and safety of multiple doses of levomilnacipran extended-release for the treatment of major depressive disorder. Neuropsychiatr Dis Treat. 2016;12:2707-14.

34 Uribe JM, Pinto DM, Vecino-Ortiz AI, Gómez-Restrepo C, Rondón MJVihri. Presenteeism, absenteeism, and lost work productivity among depressive patients from five cities of Colombia. 2017;14:15-9.

35 GDP per capita (current US$). Available on: https://data.worldbank.org/indicator/ny.gdp.pcap.cd.

36 Johnston KM, Powell LC, Anderson IM, Szabo S, Cline S. The burden of treatment-resistant depression: A systematic review of the economic and quality of life literature. Journal of Affective Disorders. 2019;242:195-210. doi:10.1016/j.jad.2018.06.045

37 Ivanova JI, Birnbaum HG, Kidolezi Y, Subramanian G, Khan SA, Stensland MD. Direct and indirect costs of employees with treatment-resistant and non-treatment-resistant major depressive disorder. Current Medical Research and Opinion. 2010;26(10):2475-2484. doi:10.1185/03007995.2010.517716

38 Greenberg P, Corey-Lisle PK, Birnbaum H, Marynchenko M, Claxton A. Economic Implications of Treatment-Resistant Depression Among Employees. PharmacoEconomics. 2004;22(6):363-373. doi:10.2165/00019053-200422060-00003

39 von Knorring L, Åkerblad A-C, Bengtsson F, Carlsson Å, Ekselius L. Cost of depression: effect of adherence and treatment response. European Psychiatry. 2006;21(6):349-354. doi:10.1016/j.eurpsy.2006.04.005

40 Sicras-Mainar A, Guijarro P, Armada B, Blanca-Tamayo M, Navarro-Artieda R. Influence of the CYP2D6 Isoenzyme in Patients Treated with Venlafaxine for Major Depressive Disorder: Clinical and Economic Consequences. de Castro F, ed. PLoS ONE. 2014;9(11):e90453. doi:10.1371/journal.pone.0090453

41 Schultz J, Joish V. Costs Associated With Changes in Antidepressant Treatment in a Managed Care Population With Major Depressive Disorder. Psychiatric Services. 2009;60(12):1604-1611. doi:10.1176/ps.2009.60.12.1604

42 Kubitz N, Mehra M, Potluri RC, Garg N, Cossrow N. Characterization of Treatment Resistant Depression Episodes in a Cohort of Patients from a US Commercial Claims Database. Quinn TJ, ed. PLoS ONE. 2013;8(10):e76882. doi:10.1371/journal.pone.0076882

43 Gibson T, Jing Y, G Carls Smith, et al. Cost burden of treatment resistance in patients with depression. The American journal of managed care. 2010;16(5):370-377. https://europepmc.org/abstract/med/20469957. Accessed July 5, 2019

44 Lepine BA, Moreno RA, Campos RN, Couttolenc BF. Treatment-Resistant Depression Increases Health Costs and Resource Utilization. Revista Brasileira de Psiquiatria. 2012;34(4):379-388. doi:10.1016/j.rbp.2012.05.009

45 Ivanova JI, Birnbaum HG, Kidolezi Y, Subramanian G, Khan SA, Stensland MD. Direct and indirect costs of employees with treatment-resistant and non-treatment-resistant major depressive disorder. Current Medical Research and Opinion. 2010;26(10):2475-2484. doi:10.1185/03007995.2010.517716

the clinical & economic burden of treatment resistant … · 2021. 4. 12. · aly akram erfan...

Documents