www.sciformix.com

With the emergence of value based payments (VBP), real world evidence (RWE) is becoming ever more relevant. RWE is used to assess a product’s safety, efficacy to effectiveness translation, cost effectiveness and product differentiation1,2. It is helping payers and manufacturers to implement ‘performance-based risk-sharing agreements’ and patients to manage budgets and estimate risk benefit of interventions.

Manufacturers can leverage RWE to obtain accelerated market access and it can facilitate payers in substantiating drug pricing and reimbursement. Real World Data (RWD) can help regulatory authorities for label expansion or adding new indications of approved drugs.

The approach to collecting, evaluating and using RWD around the world, and even within individual countries, is very inconsistent and in constant flux. This is no surprise given its broad potential and the complexity of the healthcare ecosystems around the world. However, there is an increasing appetite among the wide range of stakeholders (including industry, regulators, payers, providers and patients) in harmonizing its use and impact for the overall benefit of patients. Here, we look at how RWD and RWE are evolving in Europe, the US and Asia and discuss some of the similarities and differences in the approaches being taken.

RWE in EuropeIn Europe, RWE is generally used for accelerated access to medicines and reassessment or review post launch. In the UK, the Medicines & Healthcare products Regulatory Agency (MHRA) accepts RWE as supplementary to phase 2 and phase 3 data, as well as in cases of ongoing evidence collection, whereas in Germany the Federal Institute for Drugs and Medical Devices (BfArM) maintains that Randomized Control Trial (RCT) data is the only drug-specific evidence available prior to market authorization. Other European countries have various challenges, including: limited access to data and sub-optimal IT infrastructure; long and complex reimbursement processes; and registries that are not well connected or managed. There are several pan-European initiatives underway to drive adoption of RWE, including:

The Evolution of RealWorld Evidence AcrossMultiple Geographies

• The EU and industry funded GETREAL project was designed to help bridge the gap between efficacy and effectiveness by showing how new methods of RWE collection and synthesis could be developed and considered for adoption earlier in pharmaceutical R&D and the healthcare decision-making process3. In December 2016, the project successfully launched the RWE Navigator4, a publicly available resource which provides guidance on the use of RWD, real world study designs and synthesis of RWD to a broad range of potential users.

• EMA and EUnet HTA have jointly collaborated to optimize utilization of post-licensing evidence generation for decision making by formulating

standards for data collection and analysis of RWD

including registries. Eunet HTA’s Work Package 5,

led by the French National Authority for Health (HAS),

has been established to ‘help generate, all along the

technology lifecycle, optimal and robust evidence for

health technologies (pharmaceuticals or others),

bringing benefits for patient access and public

health5.

• In 2015, the European Medicines Agency (EMA)

conducted a pilot program for their Adaptive

Pathways approval process which would make

drugs available sooner to restricted populations with

less evidence than is usually required6. The results of

the pilot caused much discussion and some concern

among European stakeholders, especially the

German Institute for Quality and Efficiency in Health

Care (IQWiG), a vocal sceptic of the adaptive

pathways concept.

• Brexit and the EMA: The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has plans to expand the use of RWD for accelerated access review and regulatory decision making; so as to ensure a smooth EU exit. The agency has listed different objectives for optimizing RWD use; including proactive regulatory surveillance for monitoring safety in real time.

• The Region Europe RWE Advisory Board, initiated and led by F. Hoffman-La Roche AG, was formulated to explore potential areas of RWE use in the UK, Germany, France, Italy and Poland. The board engages stakeholders including payers, providers, and patient organizations with the intent of developing a platform and widening the community for RWE. In June 2017, the board developed a three year road map of initiatives for the enhanced use of RWE7. The Board proposed 24 initiatives, with the following three deemed most important:

1. Engage in early dialogue with payers on RWE needs

2. Develop consensus exercise on the use of RWE in clinical decisions and a universal definition of patient related outcome (PRO) for active patient engagement

3. Focus on developing a model approach for data collection, mapping, data quality assessment to appropriately collect PRO data.

While initiatives such as those outlined above aim to take RWE in Europe to the next level, there are numerous examples where RWE is already being used effectively in various countries. Just a few examples are shown in the table below.

www.sciformix.com

With the emergence of value based payments (VBP), real world evidence (RWE) is becoming ever more relevant. RWE is used to assess a product’s safety, efficacy to effectiveness translation, cost effectiveness and product differentiation1,2. It is helping payers and manufacturers to implement ‘performance-based risk-sharing agreements’ and patients to manage budgets and estimate risk benefit of interventions.

Manufacturers can leverage RWE to obtain accelerated market access and it can facilitate payers in substantiating drug pricing and reimbursement. Real World Data (RWD) can help regulatory authorities for label expansion or adding new indications of approved drugs.

The approach to collecting, evaluating and using RWD around the world, and even within individual countries, is very inconsistent and in constant flux. This is no surprise given its broad potential and the complexity of the healthcare ecosystems around the world. However, there is an increasing appetite among the wide range of stakeholders (including industry, regulators, payers, providers and patients) in harmonizing its use and impact for the overall benefit of patients. Here, we look at how RWD and RWE are evolving in Europe, the US and Asia and discuss some of the similarities and differences in the approaches being taken.

RWE in EuropeIn Europe, RWE is generally used for accelerated access to medicines and reassessment or review post launch. In the UK, the Medicines & Healthcare products Regulatory Agency (MHRA) accepts RWE as supplementary to phase 2 and phase 3 data, as well as in cases of ongoing evidence collection, whereas in Germany the Federal Institute for Drugs and Medical Devices (BfArM) maintains that Randomized Control Trial (RCT) data is the only drug-specific evidence available prior to market authorization. Other European countries have various challenges, including: limited access to data and sub-optimal IT infrastructure; long and complex reimbursement processes; and registries that are not well connected or managed. There are several pan-European initiatives underway to drive adoption of RWE, including:

• The EU and industry funded GETREAL project was designed to help bridge the gap between efficacy and effectiveness by showing how new methods of RWE collection and synthesis could be developed and considered for adoption earlier in pharmaceutical R&D and the healthcare decision-making process3. In December 2016, the project successfully launched the RWE Navigator4, a publicly available resource which provides guidance on the use of RWD, real world study designs and synthesis of RWD to a broad range of potential users.

• EMA and EUnet HTA have jointly collaborated to optimize utilization of post-licensing evidence generation for decision making by formulating

standards for data collection and analysis of RWD

including registries. Eunet HTA’s Work Package 5,

led by the French National Authority for Health (HAS),

has been established to ‘help generate, all along the

technology lifecycle, optimal and robust evidence for

health technologies (pharmaceuticals or others),

bringing benefits for patient access and public

health5.

• In 2015, the European Medicines Agency (EMA)

conducted a pilot program for their Adaptive

Pathways approval process which would make

drugs available sooner to restricted populations with

less evidence than is usually required6. The results of

the pilot caused much discussion and some concern

among European stakeholders, especially the

German Institute for Quality and Efficiency in Health

Care (IQWiG), a vocal sceptic of the adaptive

pathways concept.

• Brexit and the EMA: The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has plans to expand the use of RWD for accelerated access review and regulatory decision making; so as to ensure a smooth EU exit. The agency has listed different objectives for optimizing RWD use; including proactive regulatory surveillance for monitoring safety in real time.

• The Region Europe RWE Advisory Board, initiated and led by F. Hoffman-La Roche AG, was formulated to explore potential areas of RWE use in the UK, Germany, France, Italy and Poland. The board engages stakeholders including payers, providers, and patient organizations with the intent of developing a platform and widening the community for RWE. In June 2017, the board developed a three year road map of initiatives for the enhanced use of RWE7. The Board proposed 24 initiatives, with the following three deemed most important:

1. Engage in early dialogue with payers on RWE needs

2. Develop consensus exercise on the use of RWE in clinical decisions and a universal definition of patient related outcome (PRO) for active patient engagement

3. Focus on developing a model approach for data collection, mapping, data quality assessment to appropriately collect PRO data.

While initiatives such as those outlined above aim to take RWE in Europe to the next level, there are numerous examples where RWE is already being used effectively in various countries. Just a few examples are shown in the table below.

Sweden The Swedeheart Study, a national registry of coronary artery disease care and valvular interventions, has been found to improve the quality of care, outcomes and costs (Jernberg et al.).

Italy AstraZeneca prevented the generic reference pricing of its drug Crestor with a series of real world studies demonstrating that Crestor was able to get more patients to their LDL goal compared to generic Simvastatin.

www.sciformix.com

With the emergence of value based payments (VBP), real world evidence (RWE) is becoming ever more relevant. RWE is used to assess a product’s safety, efficacy to effectiveness translation, cost effectiveness and product differentiation1,2. It is helping payers and manufacturers to implement ‘performance-based risk-sharing agreements’ and patients to manage budgets and estimate risk benefit of interventions.

Manufacturers can leverage RWE to obtain accelerated market access and it can facilitate payers in substantiating drug pricing and reimbursement. Real World Data (RWD) can help regulatory authorities for label expansion or adding new indications of approved drugs.

The approach to collecting, evaluating and using RWD around the world, and even within individual countries, is very inconsistent and in constant flux. This is no surprise given its broad potential and the complexity of the healthcare ecosystems around the world. However, there is an increasing appetite among the wide range of stakeholders (including industry, regulators, payers, providers and patients) in harmonizing its use and impact for the overall benefit of patients. Here, we look at how RWD and RWE are evolving in Europe, the US and Asia and discuss some of the similarities and differences in the approaches being taken.

RWE in EuropeIn Europe, RWE is generally used for accelerated access to medicines and reassessment or review post launch. In the UK, the Medicines & Healthcare products Regulatory Agency (MHRA) accepts RWE as supplementary to phase 2 and phase 3 data, as well as in cases of ongoing evidence collection, whereas in Germany the Federal Institute for Drugs and Medical Devices (BfArM) maintains that Randomized Control Trial (RCT) data is the only drug-specific evidence available prior to market authorization. Other European countries have various challenges, including: limited access to data and sub-optimal IT infrastructure; long and complex reimbursement processes; and registries that are not well connected or managed. There are several pan-European initiatives underway to drive adoption of RWE, including:

• The EU and industry funded GETREAL project was designed to help bridge the gap between efficacy and effectiveness by showing how new methods of RWE collection and synthesis could be developed and considered for adoption earlier in pharmaceutical R&D and the healthcare decision-making process3. In December 2016, the project successfully launched the RWE Navigator4, a publicly available resource which provides guidance on the use of RWD, real world study designs and synthesis of RWD to a broad range of potential users.

• EMA and EUnet HTA have jointly collaborated to optimize utilization of post-licensing evidence generation for decision making by formulating

standards for data collection and analysis of RWD

including registries. Eunet HTA’s Work Package 5,

led by the French National Authority for Health (HAS),

has been established to ‘help generate, all along the

technology lifecycle, optimal and robust evidence for

health technologies (pharmaceuticals or others),

bringing benefits for patient access and public

health5.

• In 2015, the European Medicines Agency (EMA)

conducted a pilot program for their Adaptive

Pathways approval process which would make

drugs available sooner to restricted populations with

less evidence than is usually required6. The results of

the pilot caused much discussion and some concern

among European stakeholders, especially the

German Institute for Quality and Efficiency in Health

Care (IQWiG), a vocal sceptic of the adaptive

pathways concept.

• Brexit and the EMA: The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has plans to expand the use of RWD for accelerated access review and regulatory decision making; so as to ensure a smooth EU exit. The agency has listed different objectives for optimizing RWD use; including proactive regulatory surveillance for monitoring safety in real time.

• The Region Europe RWE Advisory Board, initiated and led by F. Hoffman-La Roche AG, was formulated to explore potential areas of RWE use in the UK, Germany, France, Italy and Poland. The board engages stakeholders including payers, providers, and patient organizations with the intent of developing a platform and widening the community for RWE. In June 2017, the board developed a three year road map of initiatives for the enhanced use of RWE7. The Board proposed 24 initiatives, with the following three deemed most important:

1. Engage in early dialogue with payers on RWE needs

2. Develop consensus exercise on the use of RWE in clinical decisions and a universal definition of patient related outcome (PRO) for active patient engagement

3. Focus on developing a model approach for data collection, mapping, data quality assessment to appropriately collect PRO data.

While initiatives such as those outlined above aim to take RWE in Europe to the next level, there are numerous examples where RWE is already being used effectively in various countries. Just a few examples are shown in the table below.

The US Perspective

Regulatory Outlook

In the US, the FDA has stated the need to ‘close the evidence gap between the information it uses to make decisions and the evidence increasingly used by payers and others charged with making healthcare decisions’. Since the Government is the largest payer in the US, the need for regulators and payers to align more closely is particularly acute.

The 21st Century Cures Act (Section 3037) amended the US FDA Modernization Act 114, allowing manufacturers to use RWE to support a new indication for an approved drug. By utilizing comparative PRO data and Health Care Economic Information (HCEI), manufacturers can communicate a wider scope of a product’s value to payers and formulary decision-makers. This change lowered the threshold required for proactive communication from ‘substantial evidence’ to ‘competent and reliable scientific evidence’. The scope of the legislation does not extend to the proactive communication of clinical comparisons; here, the ‘substantial evidence’ threshold still applies, requiring evidence from RCTs. The proactive use of healthcare economic information permitted through Section 114 does not extend to communication with healthcare professionals or patients. Therefore, FDA-regulated industries still face significant restrictions on their ability to communicate findings beyond the approved labeling, plus, healthcare decision-makers may not be aware of what RWE is or how to interpret it effectively.

The Netherlands The Ministry of Health negotiated funding for asthma patients who showed improvement with Xolair. Novartis will rebate the full cost of treatment to the MoH for all other patients.

The UK Primary Care Trusts (NHS administrative bodies) refused access to the first licensed treatment for Lambert–Eaton Myasthenic Syndrome (LEMS), a rare auto-immune disorder, because of real world use of an unlicensed therapy.

France Funds for the full price of schizophrenia treatment, Risperdal, were held in escrow until Janssen provided proof of lower hospitalization costs from a 12-month real world study.

In September 2016, draft Guidance was published by the FDA on the use of RWE to support regulatory decision making for medical devices8. The guidance states the FDA will evaluate the regulatory relevance of the RWD, as well as the reliability and quality of the data and data sources. Medical device manufacturer, Medtronic, signed performance to payment contracts requiring the company to reimburse hospitals for selected costs if Tyrx’s antibacterial envelope fails to prevent infection in patients who receive cardiac implants. In the recently launched working model of Pre-Cert Program for software as a medical device (SaMD), the FDA emphasized that the collection of real world performance data (RWPD) will enable pre-certified manufacturers either an exemption from pre-market review for lower risk products, or a faster review of the higher risk ones9.

The FDA aims to publish draft guidance for the use of RWE by October 202110. Earlier this year, The Institute for Clinical and Economic Review (ICER), in collaboration with the Office of Health Economics (OHE), produced guidance to payers and manufacturers on the development and use of RWE for drug coverage and formulary decisions11. It suggests the formulation of a prospective protocol, entailing contextual considerations to define the evidentiary assertion and associated evidence bar for RWE.

Other examples of how RWE is being used by industry, regulators, payers and providers in the US include:

OUTCOME

United Health have collaborated to link payments to drug performance by utilizing RWE. and Merck

Amgen and have partnered to target chronic diseases by generating RWE.Humana

Avelumab was granted accelerated approval due to supportive data from an observational study that described poor outcomes in Merkel Cell carcinoma patients treated by cytotoxic chemotherapies.

MS drug Tysabri was initially withdrawn from market due to serious adverse events, but was reintroduced under coverage with evidence development (CED) as real world studies contributed to demonstrating that benefits outweigh risks.

The Hospital utilized routine clinical data to identify a best practice for infection control leading Corporation of to significant reductions in MRSA infections.America (HCA)

Patient Outlook

Payer perspectives can influence patient access and patient perspectives can drive utilization. US payers are increasingly encouraged, via initiatives such as the IHI Triple Aim12, to consider RWE from sources such as value assessment frameworks and embark on deeper collaborations with the pharma industry.

To support the involvement of patients, The Prescription Drug User Fee Act (PDUFA) re-authorization and the 21st Century Cures Act emphasizes the use of patient data for drug development. Patients can make more informed health decisions based on information from Patient Centered Outcomes Research Institute, National Health Council, virtual networks, such as ‘Patients Like Me’, and digital technology like mHealth.

Although an emerging area of post-market access, mHealth is starting to be employed in the US. For example, Johnson & Johnson collaborated with Aetna to use wearable technology in atrial fibrillation (AFib) screening for RWE generation. They were able to identify people with asymptomatic AFib earlier and more efficiently than from routine care. Health PROMISE, a patient reported outcome tool integrated with EHRs, helped IBD patients and providers to visualize real time data; thus improving their quality of life.

Approaches to RWE in Asia

According to IMS Health, data supply issues including availability, completeness and quality, as well as gaining trust of data owners are the main challenges in Asia13. However, some data is already available and being used, or planned, for

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South Korea Public health insurance data is now open and shared by the Health Insurance Review and Assessment service (HIRA) for research and analyses. In 2006, the Positive List System (PLS) was implemented which considered cost-effectiveness of a drug as part of its approval.

Taiwan Data derived from the National Health Insurance Research Database (NHIRD) has been increasingly used to provide RWE in drug reimbursement listing as well as for making other policy decisions.

China Cardiometabolic registries have been used to research treatment outcomes for cardiovascular and metabolic diseases, and researchers have conducted a retrospective study investigating the risk of HIV transmission in serodiscordant couples.

India In Manipal hospitals, IBM’s ‘Watson for Oncology’ helps oncologists offer more personalized healthcare through the analysis of data and recommendation of evidence-based treatment options.

India In 1981 the National Cancer Registry Programme (NCRP)14 was created by the Indian Council of Medical Research (ICMR) with a network of cancer registries across the country, of which there are now 23 Population Based Cancer Registries (PBCRs).

Australia The Population Health Research Network (PHRN)15, is the country’s first national data linkage network and brings together existing health data. Research has found that net economic benefit to the Australian society of continued investment in the PHRN could be as high as $7.1 billion16.

Across Asia, much like Europe, acceptance, use and knowledge of RWE is very mixed. Countries such as Japan, Singapore and Australia with advanced medical and health related infrastructure are also comparably quite advanced in the development and adoption of RWE, whereas countries like India and China are less so17.

In 2017, Japan began its “Rational Medicine” initiative which aims to make the Japanese health care system more patient-centric and evidence-based. According to the Chief Executive of Japan’s Pharmaceuticals and Medical Devices Agency, it has the goals of providing “better insight into the risk/benefit balance of drugs, medical devices, and regenerative medical products” and creating “a medical environment where the care provided is strictly evidence based.”

Japan also has several registries and databases, including the Medical Information Database Network (MID-NET). Part of the Medical Information for Risk Assessment Initiative (MIHARI), MID-NET draws on electronic healthcare data to assess drug safety. A standardized database has been established across 10 medical institutions and full utilization will begin in 2018.

Singapore's Health Sciences Authority (HSA) launched an adaptive licensing initiative called New Drug Development Paradigms (NEWDIGS) in 2013 in collaboration with the Massachusetts Institute of Technology (MIT). Thanks to the Nation state’s small size and modern infrastructure, it is a global leader in adverse event monitoring through its hospital databases, so is well placed for further adoption of RWE.

In 2012, Australia launched its e-health program, in which it invested more than AU$1 billion and launched Australia’s Personally Controlled Electronic Health Records (PCEHR) - now called My Health Record18. Its aim was to make the health system more agile and sustainable and allow healthcare organizations to have faster, easier access to more health information for improved treatment decisions. However, widespread adoption and use of the system is still a way off, with concerns about usability and patients’ online literacy thought to be impacting uptake19.

In China, while there are registries for infectious diseases and rich hospital-level data, hospital information systems are not standardized and data is not consistently captured. In some cases medical records and files are not fully digitized, making the data even harder to access. However, with the use of modern technology such as wearable devices on the rise, the potential value of RWD is likely to influence future healthcare reform.

In India, data sources are limited. For example, health claims data is scant due to a low adoption of health insurance and EHRs along with 60% of the population living rurally. As healthcare in India is not financed by the Government, databases, medical records, and other sources of RWD have remained undeveloped. However, the Indian Health Ministry is developing legislation that would help India move toward the development and use of EHRs and improve the country’s ability to collect and store personal health data.

The healthcare systems in Australia, New Zealand, Thailand, South Korea, and Taiwan all require proof of value for money in coverage of medicines and many new patient access schemes are emerging – especially in Australia. Schemes being trialled predominantly relate to one of three scenarios20:

1. Medicines with high budget impact due to high cost per patient (e.g., adalimumab, which costs approximately $20,000 per patient-year)

2. Large volumes of use (e.g., dabigatran for prevention of stroke or systemic embolism)

3. Products that may be used beyond their approved

indications (e.g., entecavir that is subsidized only for chronic hepatitis B in adults with evidence of active liver inflammation).

Outcomes based risk sharing schemes are being trialled and adopted in Australia and Taiwan and are gaining interest in China, Hong Kong, Singapore, South Korea and Thailand21.

In 2016, a pan-Asian liver cancer/hepatocellular carcinoma (HCC) registry was established, marking an important step in the use of real world data in the region. The collaboration between The National Cancer Center Singapore (NCCS), IMS Health and the Singapore Clinical Research Institute (SCRI), aims to collect data from 2,500 patients across 35 clinical sites in nine countries.

Global Harmonization of RWE –A Long Way Off?

According to a 2017 analysis of clinicaltrials.gov, there’s a record of 321 real world studies conducted in the US, 268 in Europe, and 234 in Asia. Each region has made its own advances and has its own challenges, however much of the insight derived so far can and should continue to be pooled and shared for mutual benefit.

In Europe, the priorities for RWE appear to be early engagement with payers about the role of RWE, as well as an agreement on the definition of key data points used in RWE and a standardized approach to the collection and use of PRO data. Discussion about the safety and practicality of the advanced pathways concept continues.

In the US, regulation is starting to govern the use of RWE (in relation to medical devices) and encourage its use more broadly. However, there remain significant restrictions on FDA-regulated industries, so the concept of adaptive licensing is unlikely to gain traction any time soon.

In Asia, there is a big gulf between countries where RWD is accessible and being standardized and leveraged for RWE, and those where it is yet to exist in any formal or complete way. Australia and Taiwan are

leading the way in adopting outcomes based risk sharing schemes, with other Asian countries following their lead.

In all three regions there are countries where technology advances enable capturing RWD, but the systems, rules and safeguards are yet to catch up. When they do, accelerated market access is a real possibility. This is especially important in countries such as China, where the minimum time required from regulatory submission to subsidized access is 260 weeks (compared to 60 weeks in Japan).

For those countries that do not have suitable data infrastructure and have issues with data quality, while some adoption of RWE is possible, there is a long way to go before it will bring any real value. On the other hand, advanced markets which have sophisticated systems in place are encountering challenges with stakeholder engagement and incentives which need to be worked through.

RWD obtained from heterogeneous sources like EHRs, claims databases and registries face similar challenges, such as data accessibility, accuracy and completeness. The use of Artificial Intelligence for collecting and analyzing RWD could help close these gaps and pave the way for effective RWE use in future.

It is likely that individual and regional authorities will look overseas to learn from the approaches, successes and failures of others attempting to integrate RWE into their diverse healthcare systems.

Conclusion

It is clear that for all of the fragmented markets outlined above, a multi-stakeholder approach with international collaboration is essential to ensuring robust RWE generation and utilization. Global pharmaceutical companies have a key role to play, as do technology leaders, in encouraging standardization of concepts, processes and approaches for RWE to come close to delivering on its promise. A key imperative for organizations is to strategically utilize digital technology and artificial intelligence to enhance data availability for RWE generation.

It may not be possible, or desirable, for companies to invest in all areas of expertise required to take the most advantage of the RWE wave. Hence identifying areas that are core (and best kept internal) will help determine the right partners they need to look for. Analytics and modeling, tools to aid analytics, capture of real world data, systematic review and synthesis of information, building parts of the core value dossier are some examples of activities that can be outsourced effectively. It is also important for the partners to understand the client's portfolio and the value development framework for the products so that they can deliver the services in the most meaningful and effective manner. This is the key to building a successful RWE Center of Excellence (CoE).

www.sciformix.com

Across Asia, much like Europe, acceptance, use and knowledge of RWE is very mixed. Countries such as Japan, Singapore and Australia with advanced medical and health related infrastructure are also comparably quite advanced in the development and adoption of RWE, whereas countries like India and China are less so17.

In 2017, Japan began its “Rational Medicine” initiative which aims to make the Japanese health care system more patient-centric and evidence-based. According to the Chief Executive of Japan’s Pharmaceuticals and Medical Devices Agency, it has the goals of providing “better insight into the risk/benefit balance of drugs, medical devices, and regenerative medical products” and creating “a medical environment where the care provided is strictly evidence based.”

Japan also has several registries and databases, including the Medical Information Database Network (MID-NET). Part of the Medical Information for Risk Assessment Initiative (MIHARI), MID-NET draws on electronic healthcare data to assess drug safety. A standardized database has been established across 10 medical institutions and full utilization will begin in 2018.

Singapore's Health Sciences Authority (HSA) launched an adaptive licensing initiative called New Drug Development Paradigms (NEWDIGS) in 2013 in collaboration with the Massachusetts Institute of Technology (MIT). Thanks to the Nation state’s small size and modern infrastructure, it is a global leader in adverse event monitoring through its hospital databases, so is well placed for further adoption of RWE.

In 2012, Australia launched its e-health program, in which it invested more than AU$1 billion and launched Australia’s Personally Controlled Electronic Health Records (PCEHR) - now called My Health Record18. Its aim was to make the health system more agile and sustainable and allow healthcare organizations to have faster, easier access to more health information for improved treatment decisions. However, widespread adoption and use of the system is still a way off, with concerns about usability and patients’ online literacy thought to be impacting uptake19.

In China, while there are registries for infectious diseases and rich hospital-level data, hospital information systems are not standardized and data is not consistently captured. In some cases medical records and files are not fully digitized, making the data even harder to access. However, with the use of modern technology such as wearable devices on the rise, the potential value of RWD is likely to influence future healthcare reform.

In India, data sources are limited. For example, health claims data is scant due to a low adoption of health insurance and EHRs along with 60% of the population living rurally. As healthcare in India is not financed by the Government, databases, medical records, and other sources of RWD have remained undeveloped. However, the Indian Health Ministry is developing legislation that would help India move toward the development and use of EHRs and improve the country’s ability to collect and store personal health data.

The healthcare systems in Australia, New Zealand, Thailand, South Korea, and Taiwan all require proof of value for money in coverage of medicines and many new patient access schemes are emerging – especially in Australia. Schemes being trialled predominantly relate to one of three scenarios20:

1. Medicines with high budget impact due to high cost per patient (e.g., adalimumab, which costs approximately $20,000 per patient-year)

2. Large volumes of use (e.g., dabigatran for prevention of stroke or systemic embolism)

3. Products that may be used beyond their approved

indications (e.g., entecavir that is subsidized only for chronic hepatitis B in adults with evidence of active liver inflammation).

Outcomes based risk sharing schemes are being trialled and adopted in Australia and Taiwan and are gaining interest in China, Hong Kong, Singapore, South Korea and Thailand21.

In 2016, a pan-Asian liver cancer/hepatocellular carcinoma (HCC) registry was established, marking an important step in the use of real world data in the region. The collaboration between The National Cancer Center Singapore (NCCS), IMS Health and the Singapore Clinical Research Institute (SCRI), aims to collect data from 2,500 patients across 35 clinical sites in nine countries.

Global Harmonization of RWE –A Long Way Off?

According to a 2017 analysis of clinicaltrials.gov, there’s a record of 321 real world studies conducted in the US, 268 in Europe, and 234 in Asia. Each region has made its own advances and has its own challenges, however much of the insight derived so far can and should continue to be pooled and shared for mutual benefit.

In Europe, the priorities for RWE appear to be early engagement with payers about the role of RWE, as well as an agreement on the definition of key data points used in RWE and a standardized approach to the collection and use of PRO data. Discussion about the safety and practicality of the advanced pathways concept continues.

In the US, regulation is starting to govern the use of RWE (in relation to medical devices) and encourage its use more broadly. However, there remain significant restrictions on FDA-regulated industries, so the concept of adaptive licensing is unlikely to gain traction any time soon.

In Asia, there is a big gulf between countries where RWD is accessible and being standardized and leveraged for RWE, and those where it is yet to exist in any formal or complete way. Australia and Taiwan are

leading the way in adopting outcomes based risk sharing schemes, with other Asian countries following their lead.

In all three regions there are countries where technology advances enable capturing RWD, but the systems, rules and safeguards are yet to catch up. When they do, accelerated market access is a real possibility. This is especially important in countries such as China, where the minimum time required from regulatory submission to subsidized access is 260 weeks (compared to 60 weeks in Japan).

For those countries that do not have suitable data infrastructure and have issues with data quality, while some adoption of RWE is possible, there is a long way to go before it will bring any real value. On the other hand, advanced markets which have sophisticated systems in place are encountering challenges with stakeholder engagement and incentives which need to be worked through.

RWD obtained from heterogeneous sources like EHRs, claims databases and registries face similar challenges, such as data accessibility, accuracy and completeness. The use of Artificial Intelligence for collecting and analyzing RWD could help close these gaps and pave the way for effective RWE use in future.

It is likely that individual and regional authorities will look overseas to learn from the approaches, successes and failures of others attempting to integrate RWE into their diverse healthcare systems.

Conclusion

It is clear that for all of the fragmented markets outlined above, a multi-stakeholder approach with international collaboration is essential to ensuring robust RWE generation and utilization. Global pharmaceutical companies have a key role to play, as do technology leaders, in encouraging standardization of concepts, processes and approaches for RWE to come close to delivering on its promise. A key imperative for organizations is to strategically utilize digital technology and artificial intelligence to enhance data availability for RWE generation.

It may not be possible, or desirable, for companies to invest in all areas of expertise required to take the most advantage of the RWE wave. Hence identifying areas that are core (and best kept internal) will help determine the right partners they need to look for. Analytics and modeling, tools to aid analytics, capture of real world data, systematic review and synthesis of information, building parts of the core value dossier are some examples of activities that can be outsourced effectively. It is also important for the partners to understand the client's portfolio and the value development framework for the products so that they can deliver the services in the most meaningful and effective manner. This is the key to building a successful RWE Center of Excellence (CoE).

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Across Asia, much like Europe, acceptance, use and knowledge of RWE is very mixed. Countries such as Japan, Singapore and Australia with advanced medical and health related infrastructure are also comparably quite advanced in the development and adoption of RWE, whereas countries like India and China are less so17.

In 2017, Japan began its “Rational Medicine” initiative which aims to make the Japanese health care system more patient-centric and evidence-based. According to the Chief Executive of Japan’s Pharmaceuticals and Medical Devices Agency, it has the goals of providing “better insight into the risk/benefit balance of drugs, medical devices, and regenerative medical products” and creating “a medical environment where the care provided is strictly evidence based.”

Japan also has several registries and databases, including the Medical Information Database Network (MID-NET). Part of the Medical Information for Risk Assessment Initiative (MIHARI), MID-NET draws on electronic healthcare data to assess drug safety. A standardized database has been established across 10 medical institutions and full utilization will begin in 2018.

Singapore's Health Sciences Authority (HSA) launched an adaptive licensing initiative called New Drug Development Paradigms (NEWDIGS) in 2013 in collaboration with the Massachusetts Institute of Technology (MIT). Thanks to the Nation state’s small size and modern infrastructure, it is a global leader in adverse event monitoring through its hospital databases, so is well placed for further adoption of RWE.

In 2012, Australia launched its e-health program, in which it invested more than AU$1 billion and launched Australia’s Personally Controlled Electronic Health Records (PCEHR) - now called My Health Record18. Its aim was to make the health system more agile and sustainable and allow healthcare organizations to have faster, easier access to more health information for improved treatment decisions. However, widespread adoption and use of the system is still a way off, with concerns about usability and patients’ online literacy thought to be impacting uptake19.

In China, while there are registries for infectious diseases and rich hospital-level data, hospital information systems are not standardized and data is not consistently captured. In some cases medical records and files are not fully digitized, making the data even harder to access. However, with the use of modern technology such as wearable devices on the rise, the potential value of RWD is likely to influence future healthcare reform.

In India, data sources are limited. For example, health claims data is scant due to a low adoption of health insurance and EHRs along with 60% of the population living rurally. As healthcare in India is not financed by the Government, databases, medical records, and other sources of RWD have remained undeveloped. However, the Indian Health Ministry is developing legislation that would help India move toward the development and use of EHRs and improve the country’s ability to collect and store personal health data.

The healthcare systems in Australia, New Zealand, Thailand, South Korea, and Taiwan all require proof of value for money in coverage of medicines and many new patient access schemes are emerging – especially in Australia. Schemes being trialled predominantly relate to one of three scenarios20:

1. Medicines with high budget impact due to high cost per patient (e.g., adalimumab, which costs approximately $20,000 per patient-year)

2. Large volumes of use (e.g., dabigatran for prevention of stroke or systemic embolism)

3. Products that may be used beyond their approved

indications (e.g., entecavir that is subsidized only for chronic hepatitis B in adults with evidence of active liver inflammation).

Outcomes based risk sharing schemes are being trialled and adopted in Australia and Taiwan and are gaining interest in China, Hong Kong, Singapore, South Korea and Thailand21.

In 2016, a pan-Asian liver cancer/hepatocellular carcinoma (HCC) registry was established, marking an important step in the use of real world data in the region. The collaboration between The National Cancer Center Singapore (NCCS), IMS Health and the Singapore Clinical Research Institute (SCRI), aims to collect data from 2,500 patients across 35 clinical sites in nine countries.

Global Harmonization of RWE –A Long Way Off?

According to a 2017 analysis of clinicaltrials.gov, there’s a record of 321 real world studies conducted in the US, 268 in Europe, and 234 in Asia. Each region has made its own advances and has its own challenges, however much of the insight derived so far can and should continue to be pooled and shared for mutual benefit.

In Europe, the priorities for RWE appear to be early engagement with payers about the role of RWE, as well as an agreement on the definition of key data points used in RWE and a standardized approach to the collection and use of PRO data. Discussion about the safety and practicality of the advanced pathways concept continues.

In the US, regulation is starting to govern the use of RWE (in relation to medical devices) and encourage its use more broadly. However, there remain significant restrictions on FDA-regulated industries, so the concept of adaptive licensing is unlikely to gain traction any time soon.

In Asia, there is a big gulf between countries where RWD is accessible and being standardized and leveraged for RWE, and those where it is yet to exist in any formal or complete way. Australia and Taiwan are

leading the way in adopting outcomes based risk sharing schemes, with other Asian countries following their lead.

In all three regions there are countries where technology advances enable capturing RWD, but the systems, rules and safeguards are yet to catch up. When they do, accelerated market access is a real possibility. This is especially important in countries such as China, where the minimum time required from regulatory submission to subsidized access is 260 weeks (compared to 60 weeks in Japan).

For those countries that do not have suitable data infrastructure and have issues with data quality, while some adoption of RWE is possible, there is a long way to go before it will bring any real value. On the other hand, advanced markets which have sophisticated systems in place are encountering challenges with stakeholder engagement and incentives which need to be worked through.

RWD obtained from heterogeneous sources like EHRs, claims databases and registries face similar challenges, such as data accessibility, accuracy and completeness. The use of Artificial Intelligence for collecting and analyzing RWD could help close these gaps and pave the way for effective RWE use in future.

It is likely that individual and regional authorities will look overseas to learn from the approaches, successes and failures of others attempting to integrate RWE into their diverse healthcare systems.

Conclusion

It is clear that for all of the fragmented markets outlined above, a multi-stakeholder approach with international collaboration is essential to ensuring robust RWE generation and utilization. Global pharmaceutical companies have a key role to play, as do technology leaders, in encouraging standardization of concepts, processes and approaches for RWE to come close to delivering on its promise. A key imperative for organizations is to strategically utilize digital technology and artificial intelligence to enhance data availability for RWE generation.

It may not be possible, or desirable, for companies to invest in all areas of expertise required to take the most advantage of the RWE wave. Hence identifying areas that are core (and best kept internal) will help determine the right partners they need to look for. Analytics and modeling, tools to aid analytics, capture of real world data, systematic review and synthesis of information, building parts of the core value dossier are some examples of activities that can be outsourced effectively. It is also important for the partners to understand the client's portfolio and the value development framework for the products so that they can deliver the services in the most meaningful and effective manner. This is the key to building a successful RWE Center of Excellence (CoE).

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References

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About the AuthorReal World Evidence and Market Access at Sciformix Corporation.Email: Madhur.Garg@Sciformix.com