Publication

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

October 2013

1

White Paper: The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia October 2013 Prepared by: Vladimir Misik, PhD Sr Director Clinical Operations, Quintiles [email protected] Mohammed Al-Sultan, PhD Managing Director, Saudi Ajal [email protected] Rachel Brady, Sr Research Analyst, Quintiles [email protected]

In collaboration with 2

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

October 2013

3

Table of Contents

Executive Summary 4 .......................................................................................... ...................................................................................................... Introduction 5 The Value of Clinical Trials 7 ................................................................................ Global Competition for Industry-Sponsored Clinical Trials .............................

10

United Kingdom 13 .................................................................................... Canada 15 ................................................................................................. Germany 16 ............................................................................................... United States 16 ........................................................................................

Central + Eastern Europe and CIS countries .....................................

17

................................................................................................... Poland 17

.................................. TMENA (Turkey, Middle East and North Africa)

18

................................................................................................... Turkey 18 United Arab Emirates 19 ........................................................................... Healthcare and Clinical Trial Landscape across MENA and Saudi Arabia .....

20

Recommendations to increase presence of clinical trials in Saudi Arabia 24 ..... ............................................. Value Potential of Clinical Trials to Saudi Arabia

30

......................................................................................................... Appendix A 32 ......................................................................................................... References 33

4

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

October 2013

5

Executive Summary

Introduction

Industry-sponsored clinical trials can play a significant role in supplementing domestic healthcare structures in a multifaceted way. Through participation in clinical trials, patients have access to innovative medicines and advanced technology that would be otherwise unavailable. In addition, industry-sponsored clinical trials attract highly qualified clinicians, providing jobs for skilled personnel and can have a significant impact on the national healthcare system through the partial funding of treatments for the participants. The Kingdom of Saudi Arabia (“KSA”) has historically been disproportionately underrepresented in clinical trials and thus unable to fully enjoy the associated societal benefits. The Kingdom claimed a paltry 0.017% of global industry-sponsored R&D clinical trial sites in the 2010-2012 period (with an estimated USD 5.6 million in revenues), which contrasts with expected share of consumption of developed products (KSA’s share of global consumption of biopharmaceuticals in 2020 of ~ 0.7%), suggesting a 40x under-representation in development of new products relative to their future consumption. This presents a significant scientific and ethical dilemma as a significant percentage of products on the market would lack appropriate representation of the Kingdom’s population in their development, resulting in consumption of medicines without prior knowledge of the efficacy and safety on the local population. It is therefore important for KSA to stake claim to increased participation in industry R&D clinical trials, as the biopharmaceutical industry increasingly moves parts of development programs outside of the traditional markets of North America and Western Europe in search of ways to shorten the duration of clinical trials and reduce the cost per patient. This may now serve as an advantage for KSA as there is a significant untapped and often treatment-naïve patient population with high disease prevalence, which would readily be available for enrolment into clinical trials. Furthermore, the presence of numerous world-class medical facilities and increasing numbers of western-trained investigators as well as rapidly growing healthcare investments, contribute to enhancing Saudi Arabia’s attractiveness to the pharmaceutical industry. The Kingdom’s participation in clinical trials should strive to achieve market share levels comparable to that of consumption of developed products, which would result in estimated annual clinical trial revenues in excess of USD 200 million (up from current levels of ~USD 5m), conditioned by the creation of an environment which is attractive and supportive of industry-sponsored research and development clinical trials.

A healthy population supported by a well established medical infrastructure contributes greatly to the dynamic economic growth and stability of a nation. Conversely, the economic and social burden of illness can be tremendously devastating for individuals, healthcare systems and countries (1). The availability and cost of treatment are of immediate concern while intangible consequences such as an undetermined length of absence from employment resulting in loss of income and employment can have lasting effect. Furthermore, the burden of caring for the sick tends to involve relatives potentially affecting their availability for employment and exposing themselves to illness as well. Without a comprehensive public health infrastructure in place, large sections of society can be adversely affected having a direct impact on the productivity and economic growth of a nation as a whole. According to one study, the surging occurrence of diabetes alone is estimated to have exceeded $0.87 billion for the national healthcare system in Saudi Arabia in 2010 (2). In the 2011 United Nations Human Development Indicators report considering health, education and income factors, the Kingdom of Saudi Arabia was ranked 56th out of 187 countries globally, scoring higher than the Arab states as a whole and just above the threshold for high human development (3). While there has been marked improvement in the past years, room for development still remains. When compared with the United States and United Kingdom as a benchmark, the disparity between standard healthcare indicators as shown in Table 1 actively contributes to a competitive disadvantage on a broader scale (4). Table 1. Comparison of standard healthcare Life Expectancy at Birth Saudi Arabia United States United Kingdom

73.9 78.2 80.4

Total Health Expenditure (% GDP) 4.3 17.9 9.6

Hospital Beds per 1,000 people (2009) 2.2 3 3.3

Physicians per 1,000 people 0.9 2.3 2.7

Source: The World Bank. Health, Nutrition and Population Statistics. 2010 (5)

6

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

October 2013

7

The Value of Clinical Trials Industry-sponsored clinical trials can play a significant role in supplementing domestic healthcare structures in a multifaceted way. Clinical trials consist of series of tests and rigorous analyses on a newly developed or enhanced compound, drug or device intended to improve the health of the consumer. Through participation in clinical trials, patients have access to innovative medicines and advanced technology that would be otherwise unavailable. In addition, industry-sponsored clinical trials can have a significant impact on the national healthcare system through the partial funding of treatments for the participants. Furthermore, the conduct of clinical trials requires numerous personnel-creating jobs and contributes to skills development. Skilled physicians are often attracted to participate in clinical trials due to the opportunity to garner first-hand experience with innovative drugs and technologies as well as the exposure to and collaboration with international colleagues. This in turn enhances the reputation and strength of the healthcare institutions involved. During the past decades, the biotech and pharmaceutical industry (“biopharma”) has increasingly moved parts of its development programs outside of the traditional markets of North America and Western Europe in search of ways to shorten the duration of clinical trials and reduce cost per patient (6) (7) (8). Saudi Arabia has historically been disproportionately underrepresented in clinical trials and thus unable to fully enjoy the associated societal benefits. However, this may now serve as an advantage as there is a significant untapped and often treatment-naïve patient population with high disease prevalence, many with orphan status, which would readily be available for enrollment into clinical trials. Furthermore, the presence of numerous world-class medical facilities and increasing numbers of western-trained investigators as well as rapidly growing healthcare investments, contribute to enhancing Saudi Arabia’s attractiveness to the pharmaceutical industry. This report will discuss the importance of industry-sponsored clinical trials and the benefits that are brought to all participants from patients to the national level and contemporary actions that countries worldwide are taking to attract more clinical trials. Analysis will be conducted regarding the displayed interest of sponsors across Turkey, Middle East and North Africa (“TMENA”) region and the trending of clinical trial sites globally, regionally and locally. While this paper does not intend to outline specific solutions, recommendations will be made at the end for areas of focus and further development.

8

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

Clinical trials respond to human, social and financial goals as they relate to the development of new drugs, devices and vaccines. They are the nexus between science and practice and reveal crucial information about the products they test. In the long term, they will result in the ability to cure or cope with disease, improve quality of life, and prevent decline or disability. In the immediate term, they are important to our understanding of disease, generate knowledge that is used in many different ways in both industry and patient care settings and offer patients and clinicians rare opportunities for novel and advanced treatment options (9). Often patients are further incentivized to participate in order to gain access to highly qualified clinicians and facilities that may otherwise be unavailable. Research and development (“R&D”) clinical trials pass through three stages before a drug is approved and sold for consumption. ► Phase 1: the experimental drug or therapy is given to either a small number of healthy human subjects or, depending on the type of molecule, on patients (< 100) to evaluate the safety, determine a safe dosage range and identify any side effects. ► Phase 2: the treatment is given to a larger group of patients (100 – 500) to evaluate its effectiveness and further evaluate its safety. ► Phase 3: the largest stage in which the treatment is administered to large groups of patients (1,000 – 5,000) to determine effectiveness, further monitoring of side effects and compare with placebo and/or other available treatment options. Once completed, data from successful clinical trials help to market and monitor safe use of the drug, device or vaccine. ► Phase 4: studies and registries are conducted after commercial launch of a product to further monitor safety and efficacy profile in real world settings and often in comparison with other available treatment options.

October 2013

9

Clinical trials attract the world’s leading clinicians and create employment opportunities for thousands of highly qualified personnel. Finally, they generate important revenues for organizations and for the economy, a consideration which is intimately tied to the well-being of society (9). Patients – Patients and their families are perhaps the greatest beneficiaries of participation in clinical trials. Regardless of the standard of healthcare in the country, clinical trials offer access to cutting-edge medical technology and innovative therapies to a select group of participants. Furthermore, as these studies are closely monitored to ensure safety, patients have greater access to highly qualified physicians providing confidence in the care they receive. In addition to personal care, many subjects are also motivated to participate in clinical trials as a means to contribute to the development of science and medicinal breakthroughs for future generations. Clinicians – Participation in clinical trials allow clinicians to gain knowledge and first-hand experience with innovative drugs and potential side effects – resulting in invaluable confidence and competence when prescribing these medicines to future patients. Studies have confirmed a positive correlation between physicians participating in clinical trials and their subsequent prescription of the new first-in-class drugs (10). Furthermore, participation in trials brings personal benefit to doctors as they have increased exposure to sought after cutting-edge research and technology as well as fostering positive international collaboration among clinical investigators. In a recent survey of investigators, over 50% listed advancement in scientific knowledge and the opportunity for scientific publication as personal incentives for participation (11). Healthcare institutions – Participation in clinical trials not only enhances the quality of medical staff participating in them, but is also known to attract leading clinicians, resulting in better clinical outcomes for the organization. It can also reinforce the development of centers of excellence – through a cyclical combination of trials, outcomes, critical mass, patient choice, leading clinicians, grants, prestigious reputations, donations for technology and equipment, academic mission and the bench to bedside paradigm (12).

10

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

Economy – Carrying out clinical trials involves large numbers of personnel-creating jobs and tremendous skills development as mentioned above. Furthermore, there is a marked increase in cash inflow for the public health system through fees and taxes paid by clinical trial sponsors, trial regulatory fees and ethical committee fees (13). In Canada, an estimated USD 300 million in potential clinical trial revenues were attracted through new clinical trial contracts in 2007-2008 (12). According to a PricewaterhouseCoopers report on Poland, there was an estimated PLN 240 million (ca. USD 40 million+) savings for the National Health Fund in 2009 for oncology studies alone, as patients received treatments that were co-financed by clinical trials sponsors (13). One should also keep in mind the number of additional service providers involved, including laboratories, courier services and translation services among others that benefit from the conduct of clinical trials. Government – The government holds significant influence, whether directly or indirectly, over the level of participation of the country in clinical trials, and hence the degree to which the above benefits are realized. The stringency of legislation (e.g. requirement of inclusion of patients in clinical development of compound submission for marketing authorization), timelines for approvals, clinical trial study material importation complexities, etc. are all factors that play into whether the country is considered for participation in a clinical trial. However, the government also stands to benefit from clinical trials. Regulatory agencies and ethics committees must be staffed and well-trained in order to ensure confidence in the population to participate in clinical trials, creating more jobs and providing greater diversification. Furthermore, through the development of these oversight agencies, the government has first-hand knowledge of the efficacy and safety of innovative medicines even before they arrive on the market, having a direct impact on the safety and health of the population and potentially reducing an increased burden on the domestic healthcare system.

October 2013

11

Global Competition for IndustrySponsored Clinical Trials During the past three decades, the pharmaceutical industry enjoyed periods of significant growth in the developed markets with sales growth outperforming GDP growth and there was little motivation to look elsewhere, with majority of clinical development for new products conducted in North America and Western Europe (8).The reliance on these traditional pharmaceutical markets for both development and consumption has been diminishing during the past decade. Presently, the situation is very different. The biotech and pharmaceutical industry (“biopharma”) has increasingly moved parts of its development programs outside of the traditional markets of North America and Western Europe, driven primarily by efforts to boost productivity through shortening the duration of clinical trials and reducing cost per patient (6) (7) (8). One of the leading causes of a missed clinical trial completion date is patient recruitment, taking up to 30 Percent of the clinical trial timeline (14). When considering that a typical patent life on an innovative compound/device is 20 years and on average it takes 10-15 years for a drug to be brought to market, any delays in the development process can have monumental consequences in terms of lost revenue, and hence lost potential research and development spend for future studies. There are numerous country-and site-specific factors at play that can impact the speed of recruitment including regulatory requirements and contracting negotiations. However, each site equally faces the challenges of recruiting as many patients as possible that meet the complex inclusion/exclusion criteria set for enrollment. It therefore stands to reason that the larger the treatment-naïve population a nation has, the greater the pool of applicable subjects for patient enrollment. Competition for a finite pool of eligible patients as well as interested and willing investigators who have time to conduct high-quality research, have proved to be challenges for countries such as the United States that have hosted clinical trials for decades and have saturated their markets to such a degree that meeting enrollment targets can be challenging. Table 2 shows the saturation of clinical trials in numerous countries and regions, comparing the number of clinical trial sites activated per 1 million inhabitants, and benchmarked against the density levels of the United States for a meaningful comparison1 (See Figure 1 and 2 for pictorial representation of global clinical trials market share and global density levels respectively) .

Table 2. Global comparison of number of clinical trial sites and clinical trials sites density. Site density levels are calculated based on the number of clinical trial sites per 1 million inhabitants and benchmarked off of United States’ density levels (US = 100%). Data includes only interventional industry-sponsored Phase 2&3 clinical trials sites. (See Table 4 for TMENA details) Region

# of Sites (2010-2012) (1)

% CT market share (1)

CT Site Density compared to US levels (2010-12) (2)

North America United States Western Europe Australia/New Zealand Japan Israel

82,661 76,059 42,745 3,909 8,983 1,648

43.83% 40.33% 22.67% 2.07% 4.76% 0.87%

96.65% 100.00% 42.14% 59.85% 28.84% 86.94%

18,103 7,545 4,824 12,120 3,106 2,751 8,088 2,212 1,599 1,574 1,168 32

9.60% 4.00% 2.56% 6.43% 1.65% 1.46% 4.29% 1.17% 0.85% 0.83% 0.62% 0.02%

57.79% 11.08% 13.82% 1.42% 0.95% 0.92% 5.55% 4.60% 0.74% 12.75% 0.73% 0.47%

EMERGING REGIONS Central Europe CIS & Russia Russia Asia (excl. Japan) China India Latin America Brazil Sub-Saharan Africa South Africa TMENA (excl. Israel) Saudi Arabia

Source: (1) ClinicalTrials.gov database. Extracted 29 July 2013 (15). (2) The World Bank. ‘Population, total’.Extracted 7 August 2013 (16).

1 In the absence of accurate global patient enrollment data, the number of active clinical trial sites has been used

as a surrogate for calculating the density levels of clinical trials sites per country.

12

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

October 2013

13

5.5 1 0.5 0.1

0

Figure 1: Percentage of interventional industry-sponsored phase 2 & 3 clinical trial sites initiated per country in 2010-12. The United States currently captures roughly 40% of clinical trials globally and has been excluded above to show the degree of differentiation among the rest of the world.

While this shift in focus stands to benefit patients in many “pharmerging” regions worldwide, the change is less welcome in some traditional markets. As can be seen in Table 3, the majority of the traditional markets, while increasing the number of clinical trials in absolute numbers, have been slowly losing market share to the emerging regions. In light of the increasing migration of clinical trials internationally and the clear health and other societal benefits clinical trials bring, many countries have attempted to bolster their attractiveness through various measures and policies. Below are snapshots of varied approaches taken by some countries to attract and retain clinical trials. The effectiveness of such measures will not be analyzed, but rather are highlighted for further discussion when considering the following questions: What makes North America and Western Europe so dependable to retain high levels of clinical trials despite their saturated clinical trial markets? What additional steps are these countries taking to ensure returning business from global biopharma? Conversely, how are some countries in emerging markets able to stand out among neighboring countries? Which currently untapped emerging countries are primed for entry to the global stage and how can these countries further enhance their attractiveness?

United Kingdom Estimated patient recruitment-related revenues from Phase 2&3 industry-sponsored clinical trials in 2012: USD 756 million2 120 50 15 4 1 0.05 0

Figure 2: Clinical trial site density of interventional industry-sponsored phase 2 & 3 clinical trials. Density is calculated as number of clinical trial sites per 1 million inhabitants and benchmarked off of US density levels (US = 100%).

14

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

The United Kingdom markets itself on internationally renowned researchers, regulations associated with high quality, the accessibility of the English language, and important research support infrastructure (9). The National Clinical Research Network (NCRN) was developed in response to a decrease in the UK’s world share of clinical trials patients. NCRN’s role is to provide practical support across the NHS, increase clinical research and involve more patients. It consists of eight national networks with 103 local branches. 2

It is estimated that annual patient-related spend is USD 28 billion globally in phase 2 and 3 R&D clinical trials (estimate based upon 2012 R&D biopharma spend). The country amounts are calculated based upon the average percentage of global market share in clinical trials in 2010-2012, extrapolated from the clinicaltrials. gov database.

October 2013

15

Four hundred organizations are members of these networks which results in thousands of clinical research sites (including primary care). Each year it funds 7,800 NHS staff and trains more than 14,000 people. Over 1,200 patients and clinicians are involved in research design, governance and delivery and 2,500 open studies recruit patients each year. In the area of study planning, it provides advice on available support staff and facilities, ideas to clinicians, and intelligence on patient populations. In the area of study set up, it reduces red tape in multi-centric studies, manages the approval process and speeds up start-up times. In the area of study delivery it funds facilities and people to carry out the research, recruits patients and provides training. The researcher costs are paid by the clinical trials sponsors, the support costs are paid by the NCRN and excess treatment costs are paid by the National Health System. As a consequence, 96% of all NHS sites have active patient recruitment into clinical trials. Table 3. Number of clinical trials sites initiated per year (Interventional, Industry-sponsored phase 2-3 clinical trial sites only). Region North America United States Western Europe Australia/New Zealand Japan Israel EMERGING REGIONS Central Europe CIS & Russia Asia (excl. Japan) Latin America Sub-Saharan Africa TMENA (excl. Israel)

Number of sites initiated 2007-09

Number of sites initiated 2010-12

# of CT Sites

%

# of CT Sites

%

Market Share Trending

81,997 75,473 41,956 3,186 6,298 1,362

46.40% 42.70% 23.70% 1.80% 3.60% 0.80%

82,661 76,059 42,745 3,909 8,983 1,648

43.80% 40.30% 22.70% 2.10% 4.80% 0.90%

     

14,658 6,765 10,096 7,574 1,648 1,122

8.30% 3.80% 5.70% 4.30% 0.90% 0.60%

18,109 7,545 12,120 8,088 1,599 1,168

9.60% 4.00% 6.40% 4.30% 0.80% 0.60%

     

Canada Estimated patient recruitment-related revenues from Phase 2&3 industry-sponsored clinical trials in 2012: USD 924 million In combination with national-level initiatives, each province has taken steps to improve the overall attractiveness for clinical trials (9). The British Columbia Clinical Research Infrastructure Network is a collaborative partnership of provincial health authorities, universities, industry associations and funding agencies. The network is focused on developing best-in-class research processes and infrastructure to support clinical and translational research personnel and activities. Task Forces have been formed to address the harmonization of research contracts, development of a pan-provincial strategy on professional development, robust quality systems in research centers and a research methodology hub of expertise. Another province, Ontario, has been active in streamlining and expediting administrative processes associated with clinical trial start-up. This includes the creation of the Ontario Cancer Research Ethics Board, a statement of principles for negotiating clinical study agreements with industry, and regional collaboration across the province to streamline ethics review and contracting processes. In April 2010, the Ontario Government launched its $161 million Life Science Commercialization Strategy, earmarking $17 million for three clinical trials-related initiatives. Stemming from this strategy, a multi-stakeholder initiative is underway with research hospitals, universities and industry to streamline the ethics review process for industry-sponsored multi-center clinical trials in Ontario, while maintaining the best-in-class standards of protection of the rights, safety and well-being of human subjects involved.

Source: Clinicaltrials.gov database. Extracted 29 July 2013 (15).

16

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

October 2013

17

Germany Estimated patient recruitment-related revenues from Phase 2&3 industry-sponsored clinical trials in 2012: USD 1.5 billion Germany places first in clinical trials conducted in Europe and second worldwide. Such services are located, for example, in one of the 45 university hospitals and 118 clinical institutes involved in clinical trials. While data quality is on par with the US, costs are up to 50 percent lower in Germany. The country’s key competitive advantage lies in the combination of lower costs for enhanced levels of expertise and quality. Numerous university hospitals around the country are renowned for their consistent and reliable collection of data in clinical trials, establishing excellent international reputations. Furthermore, the German government has identified life sciences as a decisive economic factor in the 21st century. In line with this, a number of programs – financed through public resources at national and regional levels – have been made available to the pharmaceutical industry. The German government invests approximately €4 billion in its “High-Tech Strategy” each year and provided €1.2 billion for R&D projects within the health care and biotechnology industries in 2011 (17).

United States Estimated patient recruitment-related revenues from Phase 2&3 industry-sponsored clinical trials in 2012: USD 11.3 billion In 2010, the United States held a clinical research infrastructure forum, with the vision ‘for a clinical research system that would function like an energy grid – large Public Works project to ensure universal access to new clinical evidence and its adoption by clinicians’ (9). The vision included a permanent network of resources, including sites, patients, researchers and support staff that would be available for clinical trials. The network would be organized by nodes which would have either geographic or disease-specific foci. Supporting and uniting these networks would be paid staff, academics and experts experienced in clinical trials who would support, run and organize the infrastructure. Funding would be federally provided. While this vision has supporters and opponents, many other clinical research infrastructure efforts have already been established in the US. For example, since 2006, 46 academic institutions have made up the Clinical and Translations Science Awards program. The goals are to build national, clinical and translational research capacity; provide training and career

18

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

development for clinical and translational scientists; enhance consortium-wide collaborations; improve the health of communities and the nation; advance T1 translational research to move basic laboratory discoveries and knowledge into clinical testing. In addition, the US is known internationally for its Comprehensive Cancer Systems in which 40 institutions are designated across the country. These forty institutions hold responsibility for cancer drug research and are each provided with USD 20 million per year in funding to pay for their own infrastructure, for which they also become accountable.

Central + Eastern Europe and CIS countries Among the emerging regions, the clear winner has been the CEE and CIS region, capturing more than 50% of clinical trial sites among the emerging regions (See Table 2), with Poland, Hungary and Czech Republic as the front-runners. This may in part have to do with the EU enlargement and the implementation of the European Clinical Trial directive in 2004, creating a unified legal environment across the region. Additional factors for this region include a centralized healthcare system with developed referral networks and the availability of treatment-naïve patients. Importantly, over the past decade the CEE and CIS region also earned a great reputation for quality of clinical data confirmed by audits and inspections (18), with clinical trial costs significantly lower versus North America and Western Europe.

Poland Estimated patient recruitment-related revenues from Phase 2&3 industry-sponsored clinical trials in 2012: USD 728 million In 2010, Poland was ranked 10th in the world and 2nd in Europe in terms of clinical trial market size (13). With almost 400 trials registered annually (out of the 1,000 registered for the entire CEE region), Poland has developed a positive reputation for their qualified and experienced researchers and supportive medical staff and continuous demonstration of efficient recruitment. In 2008, Poland changed the tax code to allow clinical research to be taxed in the client’s country rather than in Poland, removing VAT tax on foreign companies and granting refunds for local firms. This was seen as removing one of two critical obstacles for attracting further clinical trials (lengthy and complicated trial registration procedures being the other) (19).

October 2013

19

TMENA (Turkey, Middle East and North Africa) After nearly a decade of intense investment into the CEE +CIS region, however, it too is starting to show signs of saturation similar to traditional markets. This indicates that regions such as TMENA are primed for development as biopharma will need to start looking elsewhere to expedite their clinical trials and support their marketing needs in these rapidly growing pharmaceutical markets.

Turkey Estimated patient recruitment-related revenues from Phase 2&3 industry-sponsored clinical trials in 2012: USD 112 million With a population of 75 million (and growing) and a well-performing, sizeable economy, Turkey is firmly on the radar of all multinational corporations, including biopharma, as one of the top global emerging markets opportunities. According to a 2007 Goldman Sachs report, Turkey is considered among the top ten countries in terms of potential study subject populations. (20) The government has now set R&D advancement as one of its priorities and has resolved some of the historical problems by recently introducing a law on clinical trials and new regulation that includes many of the components of the EU directives on clinical trials. The government is also committed to tackling the problems with payments to investigators. Turkey’s hospitals are well prepared to absorb additional clinical trials and most universities have established clinical research units. Samples of government action to attract more studies include: ►

2008 law on R&D designed to attract more companies across sectors  100% tax reductions on R&D expenditure (previously 40%)  Reduced income tax for employees  Land allocations

► 2008-2009: government adopted EU directives to implement GCP guidelines  Combined with increased GCP trainings have helped to reduce past regulatory issues  Resulted in growth in the clinical research sector

20

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

► 2023 plan (21)  Objective: Improve the biopharma industry’s international competitiveness and make the industry a net exporter by improving R&D competency and increasing value-added manufacturing  Goals: Developing Basic and Clinical Research Competency and Services Exports; Developing Production Competency and Product Exports; Making Turkey a Regional Management and Service Center location for the pharmaceutical industry  After implementing the necessary changes, it is estimated that Turkey can achieve roughly USD 1.1 billion in R&D investment derived from clinical trials.

United Arab Emirates Estimated patient recruitment-related revenues from Phase 2&3 industry-sponsored clinical trials in 2012: USD 2.8 million As a result of strong population growth and increasing urbanization, the United Arab Emirates have taken numerous proactive steps to further develop its healthcare services and establish themselves as a knowledge-based society, particularly in Dubai. The opening of DuBiotech and the Dubai Healthcare City (DHCC) has aided significantly in garnering the attention of biopharma companies to the region. DuBiotech serves as the world’s first free-zone, offering 30-50 years tax exemptions, 100% foreign ownership and long-term land leases (22). The DHCC is a strategic collaboration with Harvard Medical School to provide an integrated center of excellence for clinical services, medical education and research (23). The Tawan hospital in Al Ain has also developed significant ties with the prestigious Johns Hopkins Hospital in the United States, to develop a residency exchange program between the two institutions. Additionally, the creation of the scholastic institutions such as the Dubai Harvard Foundation and the Sheikh Khalifa University of Science, Technology and Research in Abu Dhabi, create a platform for cutting-edge collaborative research and the development of sustainable research and education programs, providing a pipeline of talent for the future. The UAE has invested into its healthcare infrastructure with 14 hospitals accredited by the Joint Commission International, a renowned accreditation organization, in the past 6 years alone (23). These initiatives, in combination with the UAE’s commitment to adherence to intellectual property rights agreements and leniency on stem-cell research (just to name a few), are all contributing factors in attracting a majority of the top 10 pharmaceutical companies and with them several contract research organizations (CROs).

October 2013

21

Healthcare and Clinical Trial Landscape across MENA and Saudi Arabia The tremendous wealth accumulated through the production of natural resources and subsequent rapid growth of the economy has had a two-fold effect across the MENA (Middle East, North Africa) region. On the one hand, this has led to significant investment into the healthcare sector with modern hospital facilities and research centers with state-of-the-art equipment burgeoning across the region. A recent report from the Economist Intelligence Unit highlights MENA’s “geographical good fortune” as an additional contributing factor. Situated between the growing markets in the Asian Pacific and Africa, MENA can provide a strategic hub that, when combined with exceptional health facilities, may prove more attractive than popular emerging powerhouses such as China or India (24). Conversely, with the economic prosperity come changes in lifestyles and consumption habits. Sedentary lifestyle, low physical activity, smoking and an increasingly unhealthy diet have become an endemic part of these societies (25).The results of such changes have contributed to MENA having the second highest prevalence of diabetes in the world, where obesity levels and the prevalence of cardiovascular disease across the region are very high (and rising) and cancer – historically with lower prevalence than in the industrialized world – is also on the rise. Furthermore, a high prevalence of common genetic disorders (over 900 have been catalogued) has lead to a plethora of rare diseases, many with orphan status, including Gaucher’s disease, Fabry disease, Behcet’s disease, thalassaemia and sickle cell anemia (26). As biopharma increasingly shifts away from the blockbuster drug model to developing the orphan drug, MENA will be primed to contribute a significant number of eligible subjects, including treatment-naïve patients (27). The MENA region currently accounts for significantly less than 1% of global participation in trials. However, accelerated growth is forecast by many observers: in the next 10 years, the Middle East may account for up to 5% of global participants in trials. This growth, if achieved, would result in a research and development flow to the region from the biopharma industry in excess of USD 1 billion (28).

22

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

839 63

0

1,648

0

0

14 1 85

32

0 20

5

2 0

Figure 3: Number of all Industry-sponsored Phase 2-3 clinical trials sites initiated in 20102012. Source: ClinicalTrials.gov database, extracted 29 July 2013 (15). MENA has more to offer than just patients and centralized healthcare systems. High interest of hospitals and the motivation of doctors (investigators) to participate, governments and institutions taking proactive steps to attract clinical research, Western-trained investigators with excellent command of English and hospital source documents in English or French all contribute to promote this region. According to a recent survey of biopharma companies based outside of the MENA region, around 40% plan to increase their R&D investment into the region in the coming years (24). Despite these contributing factors, the clinical trial density (number of clinical trial sites per 1 million inhabitants) across TMENA (including Turkey) remains just below 1% of US levels and Saudi Arabia in particular is well below 1% of the clinical trial density levels in the United States (See Table 4). When combining this with the strong centralized healthcare system and the willingness of hospitals to participate the potential contribution that this region can offer is very significant.

October 2013

23

Table 4: Regional comparison of number of clinical trial sites and clinical trials sites density. Site density levels are calculated based on the number of clinical trial sites per 1 million inhabitants relative to United States’ density levels (US = 100%). Data includes only interventional industrysponsored Phase 2&3 clinical trials sites. (See Table 2 for wider global comparison) Region

# of Sites (2010-2012) (1)

% CT Market Share (1)

CT Site Density compared to US levels (2010-12) (2)

North America United States TMENA (excl Israel) Turkey Gulf Bahrain Kuwait Oman Qatar Saudi Arabia United Arab Emirates Yemen Levant Egypt Jordan Lebanon Syria North Africa Algeria Libya Morocco Tunisia

82,661 76,059 1,168 839 60 0 1 2 5 32 20 0 162 85 14 63 0 92 10 0 11 71

43.88% 40.33% 0.62% 0.40% 0.03% 0.00% 0.00% 0.00% 0.00% 0.02% 0.01% 0.00% 0.09% 0.05% 0.01% 0.03% 0.00% 0.05% 0.01% 0.00% 0.01% 0.04%

96.65% 100.00% 0.73% 4.70% 0.35% 0.00% 0.13% 0.27% 1.08% 0.47% 0.93% 0.00% 0.57% 0.44% 0.93% 5.89% 0.00% 0.44% 0.11% 0.00% 0.14% 2.73%

Source: (1) Clinicaltrials.gov database. Extracted 29 July 2013 (15). (2) The World Bank. Population, total. Extracted 7 August 2013 (16).

24

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

Saudi Arabia has more to offer than good quality hospitals where quality clinical trials can be carried out, interested investigators and a sizeable pool of patients not enrolled in clinical trials. Saudi Arabia has also been making strides towards reducing dependency on hydrocarbon revenues by developing knowledge-based economy and related institutional and governmental competencies. ► Education (24) – In an effort to transition to a knowledge-based economy, significant investment has been made into the education sector. Since 2003, the number of universities has tripled, from 8 to 24. Numerous universities currently offer the relevant infrastructure such as the newly opened Princess Noura Bin Abdul Rahman University, the only all-women’s university in the Middle East, housing a biotechnology research center, and the King Abdullah University of Science and Technology offering graduate programs in the life and physical sciences. The existence of research funds and graduate scholarship programs provided by the government will continue to encourage natural growth in these sectors for the coming generations. However, more needs to be done since a recent survey of biopharmaceutical companies showed that the quality/availability of content-knowledge skills and leadership/ management skills were of top concern when considering whether to invest into the MENA region. However, as this significant investment into education begins to bear fruit in the next decade, Saudi Arabia will be placed in a key regional position for knowledge economy including biopharma R&D. ► Cross-sector collaboration (29) (30) - For sustainable growth in the biotechnology industry, continued joint investment from the public, private and educational sectors is required. Already, signs of this collaboration can be seen. The creation of the “Comprehensive, Long-term, National Science and Technology Policy” in 2002 has been a driving force towards bringing together stakeholders interested in developing the science and technology innovation capabilities in the country, with the goal to place the Kingdom as a regional leader in innovation by 2015. Stemming from this plan, one of the key partners, the King Abdulaziz City for Science and Technology (KACST), has developed a further initiative together with the King Faisal Specialist Hospital and Research Center, to create the National Medical and Health Research Program. The mission of this program is to “promote research in the medical and health sciences to further health and wellbeing”. Already, a number of noncommunicable and communicable diseases have been prioritized for strategic intervention.

October 2013

25

► Government infrastructure – There are numerous initiatives already in force that have placed the Kingdom of Saudi Arabia as a leader in attracting industry-sponsored clinical trials among its Gulf neighbors. Established since 2003, the Saudi Food and Drug Administration (SFDA) employs many of the US FDA regulations with respect to clinical trials. As such, the SFDA requires independent ethics committee (IEC) approval prior to receiving application for Ministry of Health approval. The usual approval time to obtain local IEC approval from each site is approximately four weeks (28). Alignment with international regulation standards aids in establishing credibility for the Saudi authority as well as streamlining the processes to match those familiar to biopharma. Another initiative includes the launch of a new national registry for clinical trials in line with WHO recommendations to ensure all clinical trials in KSA will be notified to SFDA (31). This will significantly enhance the transparency of information as well as providing knowledge of active clinical trials for the general populace, resulting in increased trust in and access to clinical trials and innovative medicines.

the driving force for filling this urgent need.

Recommendations to increase presence of clinical trials in Saudi Arabia

There remains room for growth both in attracting more clinical trials in absolute numbers as well as in standing out among neighboring countries in the region. Table 5 delineates the market share that Saudi Arabia garners across multiple regional clusters. Most striking is the steady decline in dominance among the Gulf region, not as a result of diminishing interest in Saudi Arabia, but rather due to an increasing presence of clinical trials initiated in neighboring countries. While this highlights the increasing competition in the region, it also serves as a confirmation that the Gulf countries have caught biopharma’s attention, albeit still in its formative stages.

According to the World Economic Forum’s Global Competition Index (2012-2013), Saudi Arabia ranks 18th out of 144 countries and 2nd in the region (after Qatar), highlighting the country’s macroeconomic stability (driven primarily by rising energy prices) as the main contributor for the strong ranking (32). However, when considering health and education standards, the country drops to 58th place, falling below standards in countries with similar income levels. Furthermore, in regards to the use of the latest technologies, Saudi Arabia continues to lag behind in the region and ranking 35th globally. As mentioned in the previous section, numerous initiatives and changes have already taken place in the Kingdom to improve the healthcare sector and increasingly create an environment for fostering further research and development in the life sciences fields. However, these changes are driven primarily through government structures and are significantly lacking the private investment and the organic, bottom-up growth that is needed for sustainable growth and innovation. This requires further engaging universities and relevant actors in the private sector in discussion on attracting foreign investments and encouraging civil society’s involvement in the public health discussion. Industry-sponsored clinical trials can serve as

26

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

The need for innovative drug development is driving international research and development efforts worldwide. At the center of this new innovative push is the increasing collaboration between medicine and technology. Therefore, greater emphasis should be placed on fostering partnerships with international biopharma for further research and development. The global pharmaceutical industry is expected to increase its total R&D expenses from USD 127 billion in 2010 to USD 144 billion by 2015 (21). Of this total expenditure, roughly 20% is allocated for recruitment of patients into phase 2 and 3 clinical trials or USD 28 billion 3. Such partnerships will develop not only the credibility of, but also international confidence in, the Saudi competencies and capacity for conduct of high quality clinical research. Attracting significant international investment has the capacity to serve as a catalyst for developing further domestic R&D centers helping to address the overall needs of the country for further diversification of the economy and innovative technological development.

3

Patient recruitment-related biopharma R&D expenditure has been estimated using the following assumptions: global biopharma R&D expenditure in 2012 was USD 134bn (36), of that 80% is development expenditure (37) (USD 89bn). Out of that 70% is spent on Phase 2&3 studies (38) (USD 63bn). Alternative assumptions of 53% of NME cost linked to Phase II- III trials (39) yields an estimate of USD 70bn as 2012 spend on Phase 2&3 clinical trials. Assuming that 40% of development expenditure is linked to patient recruitment (40) the estimated annual spend (at 2012 levels) on recruitment of patients into industry-sponsored Phase 2&3 clinical trial is between USD 25-28bn. Hence 1% share of CT sites represent annual patient recruitment related spend of USD 250280m at 2012 levels (this includes patient-related hospital and investigator grants, patient expenses, costs of investigational product provided to patient, national regulatory fees, ethics committees/IRB fees, local safety laboratory fees, salaries of hospital clinical trial staff (study coordinators/nurse), in-country CRO fees, customs fees & logistics of study material, courier fees, etc.)

October 2013

27

Table 5. Number of clinical trial sites initiated in the Kingdom of Saudi Arabia and the share of clinical trial sites (Interventional Industry-sponsored phase 2&3 sites only), trending over 2007-2012. (For list of country groupings, see Appendix A) KSA Share of: # of

2007

Sites

Global TMENA MENA Gulf

12

2008

2009

2010

2011

2012

Market # of Share Sites

Market # of Share Sites

Market # of Share Sites

Market # of Share Sites

Market # of Share Sites

Market Share

0.02%

0.01%

0.02%

0.02%

0.02%

0.01%

5.50% 20.34% 92.31%

8

1.89% 7.08% 80.00%

13

2.88% 9.15%

10

65.00%

2.29% 8.62% 71.43%

15

4.16% 15.00% 65.22%

7

1.97% 7.14% 30.43%

Source: Clinicaltrials.gov database. Extracted 29 July 2013 (15).

With increasing focus on the Gulf region, Saudi Arabia is well positioned to serve as a leader to drive more investment into the region. Saudi Arabia should strive to position itself as a center of excellence to export this knowledge to neighboring countries, thereby strengthening the Gulf region and the potentially the wider TMENA region as a whole. Additionally, Saudi Arabia should strive to initiate harmonization of regulatory requirements within the region as well as introduce mutual recognition of clinical trial approvals. As confidence in the region grows, Saudi Arabia, as a hub of expertise in the region, would naturally become a focal point for investment and collaboration in biopharmaceutical research. To reach this stage, greater emphasis must be placed on training and developing a wider pool of skilled workers in all related fields. The Kingdom currently faces the conundrum that too few clinical trials have provided limited experience for investigators and clinical research monitors. Inexperienced investigators and monitors cause hesitation in directing additional clinical trials to the country. This is where the collaboration between the public and private sector is most essential. While the regulatory environment has been substantially developed, the scientific curiosity must be encouraged in the private sector to further develop domestic research and development centers. This could include stipends for collegiate exchange among academic institutions, relaxing of policies hindering international recruitments and creation of funds for private sector grants focused on research, among a number of additional incentives. Considering the dominant representation of foreign physicians and academics compared to domestic representation, there is a clear need to encourage greater participation among the domestic population. A clear vision combined with substantial incentives is essential for

28

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

organically developing the unique innovation needed to help attract international investment. Essential to the development of R&D efforts in the country will be a commitment to providing continuous, current training. One report highlights requests from within the SFDA for further training and implementation of guidelines and Standard Operating Procedures to outline proper communication with international biopharma companies (33). All parties involved in carrying out and monitoring clinical trials must have a current understanding and certification in the International Conference on Harmonization-Good Clinical Practice (ICH-GCP) guidelines and such certification should be refreshed periodically to ensure high standards of compliance. Providing continuous training and skills development will be a strong incentive to pursue careers in the clinical trials field. A pool of well-trained, highly skilled individuals combined with a robust and innovative R&D sector will instill greater confidence to invest into Saudi Arabia, bringing with it in time the much needed experience for investigators and monitors to compete on the global stage. A number of additional structural changes should also be considered on the national level. Short and predictable study start-up timelines and a well-defined process in line with international standards (including identification of suitable hospitals and interested investigators, through institutional approvals to SFDA approval and importation of study material) are key for global country attractiveness. Furthermore, any administrative obstacles for both biopharmaceuticals and CROs to operate in the country should be scrutinized for its necessity. Focus should be placed on fostering institutional collaboration among leading medical institutions in the country by creating disease-specific networks aimed at raising the profile of Saud Arabia in these therapeutic areas, thereby encouraging global biopharma to utilize these competencies and capacity by placing more clinical trials in hospitals participating in such networks.

October 2013

29

Figure 4: Comparison between the percentage of global GDP and percentage of global clinical trials. The wide gap between the two figures highlights the paucity of representation in industrysponsored clinical trials and significant growth potential once changes have been implemented.

Table 6. Estimated revenue from conducting industry-sponsored, Phase 2&3 clinical trials.

% Global CTs (1)

% of Market Share

Clinical Trial Market Growoth Potential in the Kingdom of Saudi Arabia

GDP CT Linear (GDP) Linear (CT)

Source: GDP: The World Bank. GDP (Current US$). Extracted 7 August 2013 (34). CT: Clinicaltrials.gov database. Extracted 29 July 2013 (15).

The potential for growth on one side and gap between participation in development of new products and their future use is illustrated in Figure 4. Taking global share of GDP as a broad benchmark of consumption of pharmaceuticals in 2020 (35), data in Figure 4 demonstrate significant (and growing!) gap between participation in development of new biopharmaceutical products (percentage of global CT sites) and future use of developed products (percentage of global GDP used as a benchmark).

30

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

Saudi Arabia Gulf TMENA

0.02% 0.03% 0.69%

Current estimated revenue (in USD m) $5.6 $8.4 $193.2

% Global GDP 2010-2012 average (2) 0.85% 1.58% 3.95%

Estimated additional revenue based upon % global GDP levels (in USD m) $238 $442.4 $1,106

Taking this analysis a step further, when considering the growth in GDP in comparison to the relative growth of clinical trials in the Kingdom as listed in Table 7, there appears a more alarming trend. While there has been strong growth in GDP, there has been a sharp decline in the initiation of new clinical trials studies. Seen from this perspective, not only has Saudi Arabia been underrepresented in studies and thus the population bereft of early access to potentially life-saving medicines, it has experienced a significant decline that requires concerted effort to reverse. Conversely, the Gulf region has experienced strong growth across both dimensions (with the wider TMENA region experiencing slight decline in CT growth), indicating growing interest from biopharma in the region that must be tapped into.

Table 7. Comparison of GDP growth and relative clinical trials growth in 2008 and 2011 (Mid-year point of 2007-09 and 2010-12)

Saudi Arabia Gulf TMENA

2008-2011 GDP growth (1)

2008-2011 Relative CT Market Growth (2)

24.50% 24.30% 22.46%

-9.20% 30.70% -2.50%

Source: (1) World Bank. GDP (Current US$). Extracted 7 August 2013 (34). (2) Clinicaltrials.gov database. Extracted 29 July 2013 (15).

October 2013

31

Value Potential of Clinical Trials to Saudi Arabia The economic burden of aging populations and a decrease in infant mortality, combined with a growing disease profile due to an increasingly sedentary lifestyle, are factors that will undoubtedly strain the health care budgets for the Kingdom in decades to come. Increasing the presence of industry-sponsored clinical trials will have a tremendous impact on offsetting this burden. Not only will clinical trials bring innovative medicine to patients sooner and thereby curbing the length of suffering and duration of treatment, but will also supplement the costs of treatment providing immeasurable savings for the healthcare sector. Looking at the impact of diabetes alone, the number of diagnosed patients is expected to increase to 4.2 million in 2015, contributing an economic burden of approximately USD 2.4 billion for just this disease (2).

The current conditions are prime for the Kingdom of Saudi Arabia to establish itself as a regional leader in clinical trials in the near future. However, unless steps are taken to encourage private sector participation and short and predictable study start-up timelines combined with a well-defined process working to international standards (including identification of suitable hospitals and interested investigators, through institutional approvals to SFDA approval and importation of study material), biopharma may focus on neighboring countries instead, such as UAE and Turkey, which can offer similar conditions and have already outlined clear strategies to enhance their attractiveness.

If the above recommendations are implemented, the additional revenue related to the R&D clinical trials could surpass USD 200 million in Saudi Arabia (See Table 6). When combined with additional intangible benefits such as first-hand exposure to medical breakthroughs as well as increased experience and skills development with innovative technology across healthcare providers and institutions that come with conducting clinical trials, the benefits are far-reaching and can have an impact on the health sector for years to come. Not least of all, with the increased medical expertise and access to new medicines, the population as a whole benefits as the healthcare sector manages illness more effectively leading to greater productivity on the societal level. The benefits for attracting biopharma’s R&D investment into the country also extend to the potential partnerships with local universities and private sector R&D centers. Such partnerships will develop not only the credibility of but also the international confidence in the Saudi capacity for research and development. This in turn will increase the global competitiveness of Saudi Arabia economically as well as on the university level to aid in garnering greater funding and further industrial collaboration. Upon the foundation of successful and timely completion of clinical trials, the Kingdom of Saudi Arabia can further its reputation not only for attracting further domestic investment, but can begin to export the expertise and become a leader in the region. Plans should be developed for establishing Saudi Arabia as a regional clinical research hub and regional pharmaceutical development center of excellence.

32

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

October 2013

33

Appendix A Countries

References Region

Sub region

Sub-Sub region

Algeria

TMENA

MENA

North Africa

Bahrain

TMENA

MENA

Gulf

Egypt

TMENA

MENA

Levant

Iraq

TMENA

MENA

Central Asia

Jordan

TMENA

MENA

Levant

Kuwait

TMENA

MENA

Gulf

Lebanon

TMENA

MENA

Levant

Libya

TMENA

MENA

North Africa

Morocco

TMENA

MENA

North Africa

Oman

TMENA

MENA

Gulf

Qatar

TMENA

MENA

Gulf

Saudi Arabia

TMENA

MENA

Gulf

Syria

TMENA

MENA

Levant

Tunisia

TMENA

MENA

North Africa

Turkey

TMENA

Turkey

Turkey

United Arab Emirates

TMENA

MENA

Gulf

Yemen

TMENA

MENA

Gulf

1. Russell S. Illuminating Cases: Understanding the economic burden of illness through case study household research. Oxford Journals 20(5): pp. 277-289 (September 2005). 2. Alhowaish A. Economic costs of diabetes in Saudi Arabia. Journal of Family and Community Medicine 20(1): pp 1-7 (April 2013). 3. United Nations Development Program. International Human Development Indicators. Available from: http://hdrstats.undp.org/en/countries/profiles/SAU.html. 4. Strategic Priorities for Advance Medical Health Research. Funded by the King Abdulaziz City for Science and Technology and the Kingdom of Saudi Arabia Ministry of Economy and Planning. 5. The World Bank. Health Nutrition and Population Statistics. Avaialble from: http://databank. worldbank.org/data/home.aspx. 6. European Medicines Agency. Reflection paper on ethical and GCP aspects of clinical trials of medicinal products for human use conducted in third countries and submitted in market authorization applications to the EMA. London, May 2010. Ref. EMA/712397/2009. 7. Glickman SW, McHutchinson JG, Peterson ED, Cairns CB, Harrington RA, Califf RM and Schulman KA, Ethical and scientific implications of the globalization of clinical research. New England Journal of Medicine 360(8): pp 816-823 (2007). 8. Misik V. Shifting Sands. European Pharmaceutical Contractor, pp 66-70 (September 2011). 9. Entire paragraph taken from Canada’s Research-Based Pharmaceutical Companies, et al. Canadian Clinical Trial Summit: Starting the Conversation. Ottawa, October 2011. 10. Corrigan M. and Glass H. Physician Participation in Clinical Studies and Subsequent Prescribing of New Drugs. Pharmacy & Therapeutics 30(1): pp 60-66 (2005). 11. Karlberg J. Globalization of Industry-Sponsored Clinical Trials and Challenges and Opportunities for Asia Clinical Trials Centre. The University of Hong Kong, 2011. Presentation slides. 12. Canada’s Research-Based Pharmaceutical Companies, et al. Canadian Clinical Trial Summit: Starting the Conversation. Ottawa, October 2011. 13. PricewaterhouseCoopers. Clinical Trials in Poland – Key Challenges. p. 46, November 2010.

34

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

October 2013

35

14. Bachenheimer J and Brescia BA. Reinventing Patient Recruitment: Revolutionary Ideas for Clinical Trial Success. Gower Publishing. (2007). 15. Analysis of global clinical trials data extracted from the Clinicaltrials.gov data base, a service of the U.S. National Institutes of Health. Extracted 5 October 2012. Available from: http://www. clinicaltrials.gov 16. The World Bank. Population, Total. Extracted 7 August 2013. Available from: http://www. Available from: http://www.data.worldbank.org/indicator/SP.POP.TOTL 17. All data pulled from: Germany Trade and Invest. The Pharmaceutical Industry in Germany: Industry Overview, Issue 2011. 18. Samsonov M. Clinical Trials in Central and Eastern Europe. World Pharmaceutical Frontiers pp: 74-75. 19. Taylor P. Poland set to remove tax block for clinical trials. Outsourcing-Pharma, November 2008. Available from: http://www.outsourcing-pharma.com 20. Virk KP. Turkish Delight. International Clinical Trials, Winter (2011). 21. PricewaterhouseCooper and Association of Research-based Pharmaceutical Companies. Turkey’s Pharmaceutical Sector: Vision 2023 Report, Strategy Document.

29. King Abdulaziz City for Science and Technology. Annual Report. (1432 – 1433 AH), 2011. 30. King Abdulaziz City for Science and Technology and Kingdom of Saudi Arabia Ministry of Economy and Planning. Strategic Priorities for Advanced Medical and Health Research. Date unknown. 31. Al-Farhan M. and Shahrouri R. Interview: Saudi Food and Drug Administration. Journal for Clinical Studies, p 20 (July 2010). 32. World Economic Forum. The Global Competative Index 2012-2013: Country Profile Highlights. Available from: http://www.weforum.org 33. Al-Essa R, Salek S, Walker S. Regulatory Review Process in the Gulf Cooperation Council States: Similarities and Differences. Drug Information Journal 46(1): pp 65-72 (2012). 34. The World Bank. GDP (Current US$). Extracts 7 August 2013. Available from: http;//www.data. worldbank.org/indicator/NY.GDP.MKTP.CD 35. UBS Investment Research. Global pharma: Doing well by doing good?, Q-Series: UBS World Pharma Model. 2010 Sep; pp 1-22. [cited: 31 July 2013]. Available from: http://www. accesstomedicineindex.org/sites/www.accesstomedicineindex.org/files/publication/UBS_full_ report_0.pdf. 36. EP Vantage. Novartis set to remain top spender as R&D investment dips. 18 June 2012.

22. Tylor N. UAE makes big efforts to attract pharma. June 2009, Available from: http://www.inpharmatechnologist.com.

37. UBS Investment research. New Coverage - CROs: Down, But Not Out, Contract Research Organizations. 15 December 2009; pp 1-40.

23. Tadmouri A. Middle East: New Frontier for Medical Device Clinical Evidence. 2011

38. Desai PB, Anderson C, Sietsema WK. A comparison of the quality of data, assessed during query rates, from clinical trials conducted across developed versus emerging global regions. Drug Information Journal 46(6) pp 455-463 (2012).

24. Economist Intelligence Unit. Laying the Foundations: A new era for R&D in the Middle East. (2011). 25. Abraham R. MENA: The Dawn of a New Era. Applied Clinical Trials, pp: 36-42 (April 2011). 26. Al-Gazali L, Hamamy H and Al-Arrayad S. Genetic disorders in the Arab world. BMJ 333: p 831 (2006). 27. Mintz C. Orphan Drugs: Big Pharma’s Next Act?. Life Science Leader. Date unknown.

39. Paul SM, Mytelka DS, Dunwiddie CT, Persinger CP, Munos BH, Lindborg SR, Schacht AL. How to improve R&D productivity. Nature Reviews 9; pp 203-214, (March 2010). 40. Sahoo A. The CRO market outlook to 2016. SCRIP Business Insights. November 2011. Ref. code BI00046-006.

28. Chin R. and Bairu M. Global Clinical Trials: Effective Implementations and Management. London: Elsevier Inc. ( 2011).

36

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

October 2013

37

38

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia

October 2013

39

40

The Value of Industry-Sponsored R&D Clinical Trials to Saudi Arabia