Madhur Garg, Real World Evidence and Market Access, Sciformix, a Covance Company04.05.19
The emergence of value based payments (VBP) has highlighted the importance and relevance of real world evidence (RWE). RWE is used to assess a product’s safety, efficacy to effectiveness translation, cost effectiveness and product differentiation,1,2 thus 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 with regulatory approval of label expansion or new indications for marketed drugs.
However, the approach to collecting, evaluating and using RWD around the globe is very inconsistent. There is an increasing desire among a wide range of stakeholders—including industry, regulators, payers, providers and patients—to harmonize its use and impact for the overall benefit of patients. This article investigates how RWD and RWE are evolving across the U.S., Europe and Asia.
The U.S. Perspective
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.’ As the government is the largest payer in the U.S., the need for regulators and payers to align more closely is particularly acute.
The 21st Century Cures Act (Section 3037) amended the U.S. FDA Modernization Act 114, allowing manufacturers to use RWE to support a new indication for an approved drug. By utilizing comparative Patient Reported Outcomes (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’.
In September 2016, draft Guidance was published by the FDA on the use of RWE to support regulatory decision making for medical devices.3 The guidance states the FDA will evaluate the regulatory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 ones.4
The FDA aims to publish draft guidance for the use of RWE by October 2021.5 In 2018, 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 decisions.6 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 U.S. is detailed in Table 1.
Table 1. Examples of RWE in use by industry, regulators, payers and providers in the US
RWE in Europe 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. However, 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 as detailed in Table 2.
Table 2. European initiatives underway to drive adaoption of RWE
The Asia Perspective
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 Asia.11 However, some data is already available and being used, or planned, as shown in Table 3.
Table 3. Data already available and being used, or planned, across Asia
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 so.15
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.”
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). Due to its 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 Record.16 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 uptake.17
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 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.
Summary
It is clear a multi-stakeholder approach with international collaboration is essential to ensuring robust RWE generation and utilization. Global pharmaceutical companies play a pivotal role in encouraging standardization of concepts, processes and approaches for RWE. A key imperative for organizations is to strategically utilize digital technology and artificial intelligence to enhance data availability for RWE generation. There are some additional examples of how blockchain and data analytics, within RWE, will be used to incentivize right health outcomes in the healthcare ecosystem.18,19
Recent developments in the mergers and acquisitions (M&A) space have showed enough investor appetite towards funding game-changing health delivery models. An example of this includes Amazon’s acquisition of online pharmacy PillPack which looks at removing the middlemen in the pharmacy supply chain. The Amazon, JPMorgan Chase and Berkshire Hathaway joint venture has indicated its aim to lower health insurance coverage costs for employees among other things.20 These examples show, overall, RWE will be a key driver in the transition towards value based healthcare.
It may not be possible for companies to invest in all areas of expertise required to take advantage of growth in RWE. Hence, identifying areas that are core 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 a few 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.
References
1. Alison Cave, 2016. What are the real-world evidence tools and how can they support decision making.
2. U.S. Department of Health and Human Services, Food and Drug Administration, 2017. Use of Real-World Evidence to support regulatory decision-making for medical devices.
3. Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices –Draft Guidance, FDA, September, 2016
4.https://www.fda.gov/downloads/MedicalDevices/NewsEvents/WorkshopsConferences/UCM597303.pdf
5.https://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM511438.pdf
6. ICER (2018). Real World Evidence for Coverage Decisions: opportunities and challenges / Understanding the Context, Selecting the Standards: A Framework to Guide the Optimal Development and Use of Real World Evidence for Coverage and Formulary Decisions
7. http://www.imi-getreal.eu/News/ID/88/European-Commission--a-succes-story-IMI-GetReal
8. https://www.eunethta.eu/ja3-archive/work-package-5-life-cycle-approach-to-improve-evidence-generation/
9.http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000601.jsp
10. Gill, J.L., d’Angela, D., Berger, K., Dank, M., Duncombe, R.,Fink-Wagner, A-H., Hutton, J., Kössler, I., Podrazilova, K.,Thomas, M. and Kanavos, P.G. (2017). RWE in Europe Paper IV: engaging pharma in the RWE Roadmap.
11. Tan, Seng C. (2015) Staying ahead of your competitors in evidence-based world: models for success.
12. http://www.ncdirindia.org/ncrp/About_NCRP.aspx
13. http://www.phrn.org.au/
14. Lateral Economics (October 2017). Population Health Research Network (PHRN) Impact and Return on Investment.
15. https://www.pharmafocusasia.com/clinical-trials/use-real-world-evidence
16. https://www.myhealthrecord.gov.au/
17. Walsh, Louisa et al. “The E-Health Literacy Demands of Australia’s My Health Record: A Heuristic Evaluation of Usability.” Perspectives in Health Information Management 14.Fall (2017): 1f. Print.
18. Healthcare transaction validation via blockchain proof-of-work, systems and methods, 2015. (Internet) https://patentimages.storage.googleapis.com/72/da/6f/95585e5e8709c3/US20150332283A1.pdf
19. Healthcare IT News, 2018. Why Walmart filed a patent for blockchain, wearables and EHR data (Internet) https://www.healthcareitnews.com/news/why-walmart-filed-patent-blockchain-wearables-and-ehr-data
20. Amazon’s Acquisition of PillPack, 2018 (Internet) http://www.globallegalchronicle.com/amazons-acquisition-of-pillpack/
Madhur Garg is the Director of Real World Evidence and Market Access at Sciformix, a Covance Company
However, the approach to collecting, evaluating and using RWD around the globe is very inconsistent. There is an increasing desire among a wide range of stakeholders—including industry, regulators, payers, providers and patients—to harmonize its use and impact for the overall benefit of patients. This article investigates how RWD and RWE are evolving across the U.S., Europe and Asia.
The U.S. Perspective
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.’ As the government is the largest payer in the U.S., the need for regulators and payers to align more closely is particularly acute.
The 21st Century Cures Act (Section 3037) amended the U.S. FDA Modernization Act 114, allowing manufacturers to use RWE to support a new indication for an approved drug. By utilizing comparative Patient Reported Outcomes (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’.
In September 2016, draft Guidance was published by the FDA on the use of RWE to support regulatory decision making for medical devices.3 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 ones.4
The FDA aims to publish draft guidance for the use of RWE by October 2021.5 In 2018, 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 decisions.6 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 U.S. is detailed in Table 1.
Table 1. Examples of RWE in use by industry, regulators, payers and providers in the US
RWE in Europe 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. However, 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 as detailed in Table 2.
Table 2. European initiatives underway to drive adaoption of RWE
The Asia Perspective
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 Asia.11 However, some data is already available and being used, or planned, as shown in Table 3.
Table 3. Data already available and being used, or planned, across Asia
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 so.15
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.”
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). Due to its 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 Record.16 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 uptake.17
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 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.
Summary
It is clear a multi-stakeholder approach with international collaboration is essential to ensuring robust RWE generation and utilization. Global pharmaceutical companies play a pivotal role in encouraging standardization of concepts, processes and approaches for RWE. A key imperative for organizations is to strategically utilize digital technology and artificial intelligence to enhance data availability for RWE generation. There are some additional examples of how blockchain and data analytics, within RWE, will be used to incentivize right health outcomes in the healthcare ecosystem.18,19
Recent developments in the mergers and acquisitions (M&A) space have showed enough investor appetite towards funding game-changing health delivery models. An example of this includes Amazon’s acquisition of online pharmacy PillPack which looks at removing the middlemen in the pharmacy supply chain. The Amazon, JPMorgan Chase and Berkshire Hathaway joint venture has indicated its aim to lower health insurance coverage costs for employees among other things.20 These examples show, overall, RWE will be a key driver in the transition towards value based healthcare.
It may not be possible for companies to invest in all areas of expertise required to take advantage of growth in RWE. Hence, identifying areas that are core 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 a few 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.
References
1. Alison Cave, 2016. What are the real-world evidence tools and how can they support decision making.
2. U.S. Department of Health and Human Services, Food and Drug Administration, 2017. Use of Real-World Evidence to support regulatory decision-making for medical devices.
3. Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices –Draft Guidance, FDA, September, 2016
4.https://www.fda.gov/downloads/MedicalDevices/NewsEvents/WorkshopsConferences/UCM597303.pdf
5.https://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM511438.pdf
6. ICER (2018). Real World Evidence for Coverage Decisions: opportunities and challenges / Understanding the Context, Selecting the Standards: A Framework to Guide the Optimal Development and Use of Real World Evidence for Coverage and Formulary Decisions
7. http://www.imi-getreal.eu/News/ID/88/European-Commission--a-succes-story-IMI-GetReal
8. https://www.eunethta.eu/ja3-archive/work-package-5-life-cycle-approach-to-improve-evidence-generation/
9.http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000601.jsp
10. Gill, J.L., d’Angela, D., Berger, K., Dank, M., Duncombe, R.,Fink-Wagner, A-H., Hutton, J., Kössler, I., Podrazilova, K.,Thomas, M. and Kanavos, P.G. (2017). RWE in Europe Paper IV: engaging pharma in the RWE Roadmap.
11. Tan, Seng C. (2015) Staying ahead of your competitors in evidence-based world: models for success.
12. http://www.ncdirindia.org/ncrp/About_NCRP.aspx
13. http://www.phrn.org.au/
14. Lateral Economics (October 2017). Population Health Research Network (PHRN) Impact and Return on Investment.
15. https://www.pharmafocusasia.com/clinical-trials/use-real-world-evidence
16. https://www.myhealthrecord.gov.au/
17. Walsh, Louisa et al. “The E-Health Literacy Demands of Australia’s My Health Record: A Heuristic Evaluation of Usability.” Perspectives in Health Information Management 14.Fall (2017): 1f. Print.
18. Healthcare transaction validation via blockchain proof-of-work, systems and methods, 2015. (Internet) https://patentimages.storage.googleapis.com/72/da/6f/95585e5e8709c3/US20150332283A1.pdf
19. Healthcare IT News, 2018. Why Walmart filed a patent for blockchain, wearables and EHR data (Internet) https://www.healthcareitnews.com/news/why-walmart-filed-patent-blockchain-wearables-and-ehr-data
20. Amazon’s Acquisition of PillPack, 2018 (Internet) http://www.globallegalchronicle.com/amazons-acquisition-of-pillpack/
Madhur Garg is the Director of Real World Evidence and Market Access at Sciformix, a Covance Company
