Digipharm Whitepaper EN 2.52.4 Accelerated access 2.5 Genomic profiling 12 12 13 15 19 20 02 Innovative pricing 3.1 The platform 3.1.1 Value-based healthcare delivery 3.1.2 Social

WHITEPAPER

DIGIPHARM

V2.4 (04/2019)

[email protected]

www.digipharm.io

DIGIPHARM - Healthcare Beyond Barriers. Bringing value-based healthcare to life using blockchain technology.

Table of contentsList of figuresDisclaimerAbbreviationsTermsAbstractExecutive summaryVision Solutions

030405 06 07 07 08 09

1.1 Innovative pricing and value-based healthcare1.2 Personalised medicine1.3 Data security & privacy

10 101011

01 A paradigm shift in healthcare

2.1 The requirement for innovative pricing solutions 2.2 Types of innovative pricing solutions 2.3 Current infrastructural limitations to innovative pricing 2.4 Accelerated access 2.5 Genomic profiling

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1213151920

02 Innovative pricing

3.1 The platform 3.1.1 Value-based healthcare delivery 3.1.2 Social and community care 3.1.3 Medical devices3.2 Stakeholder benefits of the REIMBURSE platform3.3 Market size

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21 24 24 252527

03 REIMBURSE

2 DIGIPHARM Whitepaper [email protected] www.digipharm.io

5.1 MYHEALTH, incentivizing patients for superior outcomes5.2 EVOLVE, supporting innovation in health

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3637

05 Pipeline projects

6.1 Overview6.2 Potential for further development 6.3 Compliance & information governance 6.4 Cyber security strategy6.5 Benefits of using the Ethereum ecosystem6.6 Benefits of using private blockchain technology 6.7 Functional architecture summary 6.8 Reimburse Platform functionality 6.9 DIGIPHARM Data lake 6.10 DIGIHEALTH 6.11 Decentralised identity services 6.12 DIGIPHARM Wallet 6.13 Additional features across platform

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383839404243 43 46 49 50 51 51 52

06 Technological considerations

4.1 The requirement for real world evidence4.2 Current challenges4.3 The INSIGHTS platform4.4 DIGIHEALTH4.5 Patient empowerment & rewards4.6 Benefits of the INSIGHTS & DIGIHEALTH platforms4.7 Market size

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29303133333435

04 INSIGHTS & DIGIHEALTH


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53 56

8.1 Health economy stakeholders 8.2 Blockchain technology & smart contract application

08 DPH health economy

9.1 DPH token use 9.2 DPH token characteristics 9.3 DIGIPHARM token economics 9.4 Commitment to charitable causes

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575959 59

09 DIGIPHARM tokens (DPH)

07 Additional services 53

10 References 60

Figure 1. How value-based pricing worksFigure 2. Current administrative infrastructureFigure 3. Additional barriers in quasi-autonomous decentralised systemsFigure 4. The REIMBURSE ecosystemFigure 5. The INSIGHTS ecosystemFigure 6. Contract confidentiality (IBM)Figure 7. Architectural processFigure 8. DIGIPHARM network functional architectureFigure 9. Single Payer – National registry – Integrated HCPFigure 10. Multi-payer – Integrated HCP Figure 11. Multi-payer/Individualised medicine – Out pocket/Co-payment – Distributed HCPFigure 12. Value-based multi payer/individual medicine including logistics distribution Figure 13. DIGIPHARM Data Lake (DDL) Figure 14. DIGIPHARM Token economics

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List of figures


This White Paper is provided by DIGIPHARM for informational purposes only. Nothing in this White Paper shall be construed as an offer to sell or buy securities in any jurisdiction, or a solicitation for investment, or an investment advice. The White Paper does not regulate any sale and purchase of DPH tokens (as referred to in the White Paper). The purchase of DPH tokens is subject to the Token Sale Terms and Conditions and the use of DPH is subject to the Platform Terms and Policies.

This White Paper describes the current vision for the DPH platforms. While we intend to attempt to realize this vision, please recognize that it is dependent on quite a number of factors and subject to quite a number of risks. It is entirely possible that platforms will never be implemented or adopted, or that only a portion of our vision will be realized. We do not guarantee or warrant any of the statements in this White Paper, because they are based on our current beliefs, expectations and assumptions, about which there can be no assurance due to various anticipated and unanticipated events that may occur. Blockchain, cryptocurrencies and other aspects of the technology used for the DPH platforms is in its infancy and will be subject to many challenges, competition and a changing environment. We will try to update our community as things grow and change, but undertake no obligation to do so. Due to the retrospective nature of regulatory action or guidance, we can make no guarantees regarding the legality of the DPH platforms or the DPH token launch in any given jurisdiction. We must operate DPH platforms in accordance with the laws of relevant jurisdictions. As such, the DPH platforms or DPH tokens may not be immediately available in certain countries.

DPH tokens are functional utility smart contracts within the DPH platforms. DPH tokens are non-refundable and are not for speculative investment. No promises of future performance or value are or will be made with respect to DPH tokens, including no promise of inherent value, no promise of continuing payments, and no guarantee that DPH tokens will hold any particular value. DPH tokens are not securities and are not a participation in DIGIPHARM. DPH tokens hold no rights in DIGIPHARM. This White Paper may be updated or altered, with the latest version of the White Paper prevailing over previous versions and we are not obliged to give you any notice of the fact or content of any changes. The latest version of the White Paper in English is available at the website [https://Digipharm.ch]. While we make every effort to ensure that all data submitted in the White Paper is accurate and up to date at the point in time that the relevant version has been disseminated, the proposed White Paper is no alternative to consulting an independent 3rd party opinion.

The White Paper does not constitute an agreement that binds DIGIPHARM. DIGIPHARM, DIGIPHARM’s directors, officers, employees and associates do not warrant or assume any legal liability arising out of or related to the accuracy, reliability, or completeness of any material contained in the White Paper. To the fullest extent permitted by any applicable law in any jurisdiction, DIGIPHARM disclaim all liability to you and everyone else in respect of the content of this White Paper, whether under any theory of tort, contract or otherwise and whether in respect of direct, indirect, consequential, special, punitive or similar damages. Persons who intend to purchase DPH tokens, should seek the advice of independent experts before committing to any action, set out in the White Paper.

Disclaimer


Acronym Expansion

AML Anti money laundering

API Application programming interface

DDL DIGIPHARM Data Lake

EHR Electronic health record

EMR Electronic medical record

FDA Food and Drug Administration

FTC Federal Trade Commission Act

FFS Fee for Service

FFP Fee-for-performance

FINMA Swiss Financial Market Supervisory Authority

FHIR Fast Healthcare Interoperability Resources

GDPR General Data Protection Regulation

HIPAA Health Insurance Portability and Accountability Act

HITECH Health Information Technology for Economic and Clinical Health Act

HITRUST Health Information Trust Alliance

HTA Health technology assessment

IEO Initial exchange offering

IOT Internet of Things

IT Information Technology

KYC Know your customer

NHS National Health Service

RWE Real world evidence

TDABC Time driven activity based costing

VBP Value-based pricing

Abbreviations


Term Definition

Value-based pricingPricing of a service or product according to the benefits it provides to a consumer

Patients The person receiving medical treatment

PayersThe entity responsible fo the financial settlement of healthcare products or services

ManufacturersTypically pharmaceutical companies that are responsible for developing and marketing therapies

ProvidersHealthcare professionals that are authorised to practice by the appropriate regulatory bodies

ReimbursementA situation where a manufacturer is paid for a pharmaceutical product by the consumer or a third party representing a consumer

Terms


Abstract DIGIPHARMs’ solutions aim to accelerate the much needed restructuring of healthcare delivery systems to a value-based approach. The inherent flaws of current global healthcare infrastructure result in substantial inefficiency, wastage and sub-optimal health outcomes for the most important stakeholder; the patient. In healthcare today, there is a lack of incentive for health systems and providers to focus on mutually beneficial collaboration and the maximisation of patient outcomes. DIGIPHARM utilises blockchain technology to overcome key infrastructural limitations to innovative pricing and evidence generation. DIGIPHARMs’ platforms drive value improvement, reward innovation and expedite the transformation to value-based, personalised healthcare.

Executive SummaryBarriers to Innovative pricing and ‘paying for performance’Healthcare systems are often required to make the difficult decision of whether to reimburse costly therapies and provide access for patients while taking into account their limited resources. Innovative pricing approaches and ‘value-based’ healthcare have the ability to overcome the challenges faced by healthcare systems when funding treatment, enabling the implementation of ‘flexible’ pricing schemes to determine the cost of treatment in relation to the benefits and ‘true value’ it delivers. Unfortunately, healthcare systems around the world lack the relevant infrastructure to efficiently track and implement innovative pricing models such as value-based pricing agreements, and so are reluctant to adopt such innovative policies. This results in patients who are most at need being denied or delayed access to novel treatments like cutting edge pharmacological therapies, an opportunity missed to decrease the long term economic and disease burden on health systems, and a barrier to reimbursement for manufacturers and healthcare providers.

Limitations of conventional real world evidenceReal world evidence (RWE) is playing an increasingly influential role in informing decision making within the healthcare industry and is crucial to informing value-based healthcare. Yet the delay of RWE outputs, the expenses of data access and the current methods of data collection negate many of the benefits of utilising these rich data resources. The lack of easily accessible and comprehensive RWE currently prevents stakeholders in healthcare to evaluate the real time performance and value provided by therapy in real life clinical practice as part of a value-based healthcare system. Additionally, patients do not have access to relevant RWE that enables them to explore health outcomes and valuable health information in accordance to their personal characteristics.


Vision

GoalsTo remove infrastructural barriers and automate the implementation of innovative pricing agreements on a fully independent platform; to facilitate reimbursement of health technology or healthcare provision according to patient outcomes for the mutual benefit of patients, payers and manufacturers.

To develop the world’s first ‘live’ RWE platform. Allowing the utilisation of real world data (RWD) as soon as it becomes available, to inform health related research, decision making for all stakeholders, including patients, and to incentivise patients to contribute their data.

DIGIPHARMs’ vision is to be ‘the pioneer of value-based healthcare delivery, innovative evidence generation and patient empowerment across the healthcare industry’ using revolutionary blockchain technology.


Solutions

INSIGHTSThe INSIGHTS platform will extract anonymised patient level data from the REIMBURSE platform and health information systems to the world’s first ‘live’ RWE database. INSIGHTS will provide a symbiotic solution with REIMBURSE to complement the progressive transformation towards value-based healthcare delivery systems. The development of a ‘live’ evidence repository will allow the integration of knowledge back into the healthcare delivery system in real time to facilitate decision making, drug development and health related research. Patients will be incentivised and rewarded to contribute their health information to the INSIGHTS platform and will gain access to up-to-date health information and personalised real world outcomes data via the DIGIHEALTH platform, something that is currently unattainable for patients worldwide.

REIMBURSEThe REIMBURSE platform harnesses the benefits of automated ‘smart contracts’ and blockchain technology; facilitating the application of truly dynamic innovative pricing solutions between healthcare systems and manufacturers, in a secure and compliant fashion with minimal administrative burden. Use of the REIMBURSE platform will expedite integration, coordination and delivery of patient centric healthcare systems with a focus on improving patient outcomes while accelerating ‘payment for value‘ mechanisms between payers, manufacturers and providers using neutrally-enforceable agreements in a peer to peer fashion.


1. A paradigm shift in healthcare1.1 Innovative pricing and value-based healthcareThe digitisation of healthcare is a key element to improving patient outcomes, their quality of life and reducing the intense burden on health systems worldwide. The healthcare industry is experiencing a paradigm shift to value-based care due to growth in demand, aging populations, chronic diseases and unsustainable levels of health related expenditure. Health systems are transitioning toward value-based care to prevent the rationing of services and increased costs for patients and payers without compromising quality of care. Provision of healthcare from a value-based perspective is based on the underlying aim of generating optimal patient outcomes relative to the monetary spend.

Healthcare systems are advancing from ‘fee-for-service’ reimbursement models to ‘fee for performance’ systems that are linked to patient outcomes. By 2020, it is estimated that 75% of commercial payments for healthcare will be executed according to value-based agreements (Deloitte 2015). For example, value-based healthcare provision will be a fairer system that incentivizes pharmaceutical companies to develop innovative drugs and be rewarded, whilst not inhibiting the access to these medicines for patients that need them most. Beyond drug therapy, this approach to commissioning is applicable to health technology such as medical devices, wider healthcare provision and social care. Value-based pricing agreements are one of a range of options within a suite of innovative pricing solutions. Ultimately, these solutions are set-up with the aim of providing access to the right healthcare, at the right time for patients and at the right cost for the healthcare system and manufacturers.

1.2 Personalised medicineAs the fields of diagnostics, molecular medicine and data capture methods develop over time, it is anticipated that tailored or targeted therapies will become widespread across most disease areas ushering in a new era of personalised healthcare. Such developments will significantly transform current industry models for research and development, treatment pathways and healthcare funding. DIGIPHARM understand the importance and necessity of value-based healthcare and next generation evidence platforms within such a dynamic environment; and is committed to leading the transformation of current market access and reimbursement practices worldwide where personalised medicine becomes the norm and no longer the exception.


1.3 Data security & privacyUtilising blockchain technology for DIGIPHARMs’ platforms promotes the development of a decentralised health information infrastructure that is ubiquitous, transparent and security conscious. In May 2017, The National Health Service (NHS) in the UK was subject to one of the largest ransomware attacks in history, crippling almost 50 NHS trusts, leaving confidential data at risk and the halt of numerous services which only added to the misfortune of patients. Such vulnerabilities of the current IT infrastructure could be mitigated by the use of an additional layer of immutable, decentralised, cryptographically encrypted platforms that are able to bypass single points of failure and continue functioning as normal. Channels of data transfer and communication from existing health information systems to DIGIPHARMs’ platforms will benefit from this additional layer of security. The development, maintenance and use of DIGIPHARM platforms will be subject to comprehensive data protection and security, advanced privacy measures and full conformance with the information governance protocols, including EU General Data Protection Regulation, outlined in section 6.6.


2. REIMBURSE, the future of innova-tive pricing and value-based reimbursement

When novel drug therapies enter the market following regulatory approval (e.g. Food and Drug Administration in the USA or European Medicines Agency in Europe) they are required to prove that they are a cost-effective use of healthcare resources, often evaluated by a formal or informal health technology assessment (HTA) process. HTA plays an essential role in supporting policy decision-making and has provided a means by which healthcare systems attempt to manage their drugs budget. Tightening healthcare budgets and ever increasing burden on health systems means that payers are less willing to carry the ‘risk’ or ‘uncertainty’ of purchasing and providing costly therapy which is only backed by clinical trial data, where patients are carefully selected under strict entry criteria and often regarded as the ‘healthiest’ among their peers. Novel therapies are substantially unproven among a greater number of patients at day-to-day clinical level, where the criteria for receiving these therapies are less strict than clinical studies and are usually affected by greater compliance issues. It is important to note that cohorts of patients that are enrolled in clinical trials typically have considerable variations in baseline characteristics and even greater variability in socio-demographic characteristics. Heterogeneous characteristics of patients translate to the varying response and efficacy that is observed at individual levels. For example, numerous studies have observed that patients of different ethnicity respond to treatment to varying degrees (Calvo et al 2006; Khrunin et al 2012; Paez et al 2004) and patients with history of smoking are likely to have a more pessimistic prognosis. Innovative pricing mechanisms are often required when new pharmacological therapies fulfil the following criteria:

2.1 The requirement for innovative pricing solutions

» There is uncertainty or concerns over the drugs efficacy in a real world setting

» Where potential consumption volumes or the incremental cost of drug compared to the

current standard of care is significant and the potential impact on the health system’s

budget is too large

» When the market for a drug is competitive and several therapies are competing for

market share

» A drug may have multiple uses and may provide different amounts of benefit for patients.

In such cases, paying the same price for the drug in all uses does not reflect ‘value for

money’


Ultimately, these challenges can lead to delays for patients in accessing much needed medication, restricted use to specific patients only and funding for the drug not being approved. For the healthcare system, this is a challenging position to be in as it wants to improve patient health, provide access to patients as soon as possible, ensure healthcare system sustainability whilst rewarding and incentivising innovation in the development of new treatments. For manufacturers, the challenges of gaining funding for their innovative drugs may disincentives future research, in addition; the requirement for robust evidence is continually growing and in some cases is becoming unrealistic to provide at the time of launch of a new drug. Innovative pricing and reimbursement solutions are also relevant for areas beyond drug therapy such as wider treatment provision, community care and medical devices.

Innovative pricing approaches have been suggested to overcome the challenges faced by patients, healthcare systems and manufacturers when assessing the funding of new health technology. Such approaches have been given many different names; value-based pricing, outcomes-based pricing, risk-sharing schemes, pay for performance, cost sharing and flexible pricing to name but a few. Theoretically, such pricing approaches have the potential to solve funding challenges associated with new drugs, yet uptake has been low and simple discounts to drug prices at the time of launch are still the most commonly used pricing solution. Complexities in national and international drug pricing regulations and the shift to value-based healthcare make simple discounts a blunt instrument that is not fit for current or future healthcare system needs. Other types of pricing models include:

2.2 Types of innovative pricing solutions

» Price/treatment capping where drugs are provided for free once a certain consumption

threshold is reached to minimise the financial impact of long term provision

» Cost sharing agreements between payers and manufacturers

» Volume-based agreements which focus on controlling expenditure within specific

budgets

» Bundled payments for wider healthcare provision


An example of an innovative pricing solution that can support sustainable and benefit driven healthcare is a value-based pricing scheme. This solution relies on a predetermined set of tangible or measurable patient-related outcomes such as time to disease progression or overall survival i.e. ‘conditions’, that are defined by interested parties, and are structured such that the healthcare system pays for the value the drug delivers when used by patients. For example, if there is uncertainty in how many cancer patients will live for at least 6 months after starting treatment. The healthcare system could enter into an agreement with a manufacturer that agrees a base-price which is adjusted up to a higher price for every patient that survives at least for 6 months and the base-price is reduced for every patient that does not (Figure 1). For wider treatment provision, these agreements could be based on conditions such as re-hospitalisation or maintaining patient quality of life. Value-based pricing schemes offer an increasingly dynamic solution where risk and uncertainty is shared between healthcare systems and manufacturers, and the level of reimbursement is linked to the overall value provided. Value-based pricing schemes conform to a ‘fee for performance’ reimbursement model linked to patient outcomes rather than pricing based on volume or units of drug consumed as a ‘fee for service’. Recently, one study showed that value-based care resulted in both cost savings and improvements in patient outcomes (Health Leaders Media 2017).


Figure 1. How value-based pricing works

In order to be implemented effectively, innovative pricing or value-based pricing models require up-to-date and accurate data to track patient progress and treatment related outcomes, and to be able to report these criteria in a compliant and validated manner. In developed countries, the clinical infrastructure to measure treatment outcomes is currently sufficient, however such resource intensive pricing models are under-utilised due to barriers in data interoperability and lack of capable infrastructure in place at administrative levels (Husereau et al 2011). Even in situations where flexible pricing schemes have been proven to be effective; payers and manufacturers are reluctant to enter such agreements due to the expenses and burden of processing the required information through every step of the reimbursement pathway and the inevitable time delays this may cause in reimbursement (Figure 2) (Carlson et al 2009; Kavanos et al 2009).

In those rare instances that flexible agreements have been implemented in practice, only single and simple pricing conditions are used and are often selected on their ease of implementation rather than the value they provide. A scheme that is slightly more complex, will inadvertently put a strain on the current workforce, who are already stretched. Italy’s National Health Service (Servizio Sanitario Nazionale) currently runs managed access agreements with similar characteristics to outcomes based reimbursement models. The Italian authorities have adopted both payments-by-results and risk sharing contracts where manufacturers must refund the full intervention costs for non-responders or refund an agreed proportion of costs for these patients every year, respectively. Retrospective reimbursement systems such as the Italian example result in delayed reimbursement and market inefficiency as a result of two steps to ‘bottom-line’ reimbursement and the long intervals between payment review. In some healthcare systems, i.e. the UK’s National Health Service (NHS), additional administrative hurdles exist due to the presence of local health trusts and clinical commissioning groups that are responsible for the planning and commissioning of healthcare services for specific regions (Figure 3).

2.3 Current infrastructural limitations to innovative pricing and value-based reimbursement


Figure 2. Current administrative infrastructure


Figure 3. Additional barriers in quasi-autonomous decentralised systems


When health systems, payers and pharmaceutical companies decide to implement innovative pricing agreements with their current administrative limitations, they are required to designate employees to monitor, track, and manually process such agreements thus resulting in substantial increases in costs and resource use (Carlson et al 2010). For example a recent outcomes based agreement for heart failure medication in the United States, with reduced hospitalisation as a sole pricing condition, was tracked using patients claims data which results in lengthy administrative process (Cigna 2016). Utilising DIGIPHARMs’ solutions would go a long way in overcoming some of the aforementioned hurdles.

‘Flexible’ pricing solutions or outcomes-based agreements (i.e. value-based) are increasingly valuable in situations where regulatory agencies have proposed ‘accelerated access schemes’ where there is an increased uncertainty in the efficacy of new therapy and the risk of providing such therapy is high for all stakeholders (Richey et al 2009). Additional reasons for the underwhelming adoption of value-based pricing agreements also include:

Such failures in the current infrastructure result in patients being denied potentially life saving treatment even though these innovative therapies are considered to provide substantial benefits. Overcoming these hurdles will ensure patients receive treatment that address their unmet needs, healthcare systems will pay a fair price for drugs or treatment thus delivering sustainable healthcare services, and manufacturers will gain funding for their novel health technologies and will be rewarded for their innovation. At a societal level, prescribers will have access to life saving and innovative medicines, being able to select from an optimal basket of therapies that will yield the best possible health outcome for their patients.

» Fragmented healthcare systems

» Inability to track patient adherence in real time

» Inconsistent practices between healthcare providers

» Patient privacy concerns

» Manual process handling - claims validation, credit note creation, adjustment

calculation

» Inability to use a ‘fit for all’ customisable platform across all regions


Recently there has been an increased number of proposals at regulatory level with regards to providing therapies that extend life and address a large unmet need at an earlier stage. The FDA will consider accelerated approval by measuring efficacy based on surrogate endpoints or something that is thought to predict clinical benefit, for example this could be based on radiographic imaging or blood biomarkers (Chuk et al 2017; Cohen et al 2003). Such predictive markers are typically available earlier than measures of patient progression or survival (primary endpoints of clinical trials are typically progression free survival or overall survival) and are likely to be the basis upon which many novel therapies are approved in the future. Expediting the approval process of therapies to treat serious diseases provides an opportunity to treat patients with increasingly innovative therapies without delay, however, uncertainty is increased with regards to treatment efficacy, adverse events and long term clinical benefit.

While drugs with accelerated approval enter the market with full FDA approval, payers are still required to assess whether and how these drugs should be paid for, especially as health insurers operate more stringent rules about which therapies they will reimburse (Gellad et al 2017). Furthermore, with increasing costs of novel therapy, accelerated approval can result in payers refusing to reimburse drugs that are yet to have proven clinical benefit in real world practice, resulting in patients being denied access to potentially life saving interventions. There is a clear opportunity to introduce dynamic value-based pricing based on surrogate endpoints that are used to inform early authorisation initiatives; in order to facilitate earlier patient access to treatment, safeguard payers and provide manufacturers with the opportunity to receive reimbursement earlier for drugs that show benefit. In January 2017 the FDA released a draft guidance (FDAMA 114) on the exchange of health economic information between manufacturers and payers, allowing manufacturers to proactively provide payers with health care economic information before a drug is approved. It is likely that the realisation of this guidance will propel and accelerate the ability of healthcare stakeholders to discuss and negotiate value-based contracting much earlier than the current reimbursement process.

2.4 Accelerated access


The drive towards personalised healthcare, supported by genomic profiling, is identifying new drugs that aim to deliver increased benefits to very specific and small patient populations (for example, instead of giving a new medicine to all breast cancer patients, the most benefit may be achieved in a subset of patients whose cancer has a specific genetic mutation). This may lead to increased pressure on healthcare systems to fund highly valuable medicines that come with a high cost for the innovation they bring.

As genomic profiling of patients to inform treatment selection is becoming more common, it is likely that value-based pricing agreements will increasingly be required to inform reimbursement decisions. Novel genomic technologies to inform patient care amplify the uncertainty around clinical efficacy and safety profiles in wider populations and are compounded by a distinct lack of data to perform robust cost-effectiveness analyses. Clinical studies in this area usually include a diverse set of participants with varied pathology, differing treatment history and heterogenous baseline characteristics; thus results from such studies may have low statistical power for some patient groups due to a smaller number of participants and uncertainty around the true factors associated with drug response. Furthermore, as we begin to be able to identify different types of patients who will benefit to different degrees from a medicine (for example, patients with and without a certain genetic mutation), this means different levels of value will be achieved in different patient groups. However, healthcare systems, in general, are poorly equipped to implement funding solutions that recognise different value of the same drug in different patient groups.

2.5 Genomic profiling

“The rapid pace of scientific advances is giving patients unprecedented hope in improving their health in ways that were not possible before. However, the demands on an already struggling healthcare system threaten society’s ability to gain maximum benefit from innovation in treatment.”


3. REIMBURSE3.1 The REIMBURSE platform

The REIMBURSE platform will harness the beneficial features of automated ‘smart contracts’, allowing the real time application of flexible pricing models and patient access schemes between healthcare providers, payers and manufacturers. Seamless integration with existing health information systems and administrative infrastructure of participating institutions will eliminate the need for manual data handling and processing of pricing and reimbursement agreements. The REIMBURSE platform will drastically reduce administrative costs currently associated with the implementation of value-based pricing schemes and potentially revolutionise drug pricing and healthcare provision as we know it today. Pre-agreed, personalised, contract stipulations will be coded on the REIMBURSE platform via an easily accessible user portal and automatically executed when contract conditions are met. REIMBURSE will also allow the implementation of exhaustive pricing conditions within the same agreement using smart contract technology. The selection of comprehensive pricing agreements will not result in any additional resource use or costs that would be incurred if detailed agreements were executed using current systems. For example, healthcare stakeholders could agree to reimburse 50% of the cost of therapy after 6 months of patient survival and 75% of therapy costs between 6 and 9 months and then 100% of the therapy cost thereafter whilst incorporating conditions based on the incidence of adverse events, disease biomarkers and reduced hospitalisations as a result of treatment, whilst circumventing any additional administrative burden.

The REIMBURSE platform will empower payers and manufacturers to negotiate meticulous pricing agreements, ranging from truly personalised schemes based on surrogate outcomes for pharmaceutical technologies to wider healthcare provision agreements applicable to patient cohorts of interest. As the healthcare industry shifts towards patient centric healthcare provision, REIMBURSE allows patients to be followed using anonymised digital identifiers, aggregating data related to patient outcomes and treatment across numerous sites. Use of the REIMBURSE platform will expedite integration, coordination and delivery of patient centric healthcare systems with a focus on improving patient outcomes while accelerating ‘payment for value‘ mechanisms between payers, providers and manufacturers using neutrally-enforceable agreements in a peer to peer fashion.


The REIMBURSE platform will allow automated dynamic pricing models to be implemented across different indications, patient subgroups, therapy lines and localities while providing consistent and comparable outputs. In the future, DIGIPHARM will be exploring the feasibility of integrating automated payment mechanisms between healthcare stakeholders. The dynamic nature of REIMBURSE will allow healthcare systems and manufacturers to manage and monitor their budgets and utilisation more effectively than is possible today via in-built key performance indicators on the user dashboard. Providing completely automated trust-based reimbursement solutions on a cryptographically encrypted platform for optimal security. REIMBURSE will accelerate a paradigm shift in pharmaceutical market access and innovative pricing whilst providing unmatchable benefits to all stakeholders.


Figure 4. The REIMBURSE ecosystem

Current obstacles REIMBURSE USPs

Trust & transparency of outcomes dataData integrity via immutable ledger and auditability

Patient privacy and confidential pricingCryptography and private permissioned blockchains

Administrative burden of tracking patient outcomes and reconciliation

Automation via ‘smart contracts’

Patient tracking and fragmented health dataDigital identities and bespoke integration engines

Payment delays and tying up of fundsAutomated settlement and invoicing mechanisms

Many platforms for contracting parties Global platform for all stakeholders

A recent KPMG report recommended keeping transaction and processing costs reasonable as

one of the key recommendations to unlocking the potential of value-based pricing (KPMG 2016).

The architecture of the platform allows increasingly dynamic and personalised

pricing solutions whilst bypassing the currently associated infrastructural barriers.


DIGIPHARM is committed to the delivery of value-based healthcare solutions beyond innovative pricing and market access solutions for pharmaceutical products. The inherent architecture of the REIMBURSE platform will further promote the progression of the wider health ecosystem to economically viable value-based practice. Development of alternative payment systems such as bundled payment models using smart contract technology, and focusing on the implementation of standardised outcome reporting frameworks with the assistance of industry thought leaders will play a key role in augmenting the mass adoption of value-based healthcare provision. Distributed ledger technology combined with scalable integration solutions also provides an intelligent solution to the embedded inefficiencies and wastage that is typically associated with health related data collection, claims adjudication and the fragmented collaboration between healthcare providers and payers. Uptake of the REIMBURSE platform will support the amalgamation of healthcare delivery between siloed and fragmented institutions to organise care for distinct patient cohorts whilst serving as a common platform to address allocative efficiency concerns using methods such as time driven activity based costing (TDABC).

3.1.1 Value-based healthcare delivery

There is a growing interest in value-based commissioning within the social and community care sectors. Through the implementation of outcomes collection and reporting by care providers in the community using digital tools, DIGIPHARM seek to enable incentivisation mechanisms for providers as a result of value-based commissioning and realising the associated benefits for patients and health systems. Outcomes collection in community settings is not currently standard practice and exists as an obstacle that can be readily overcome. DIGIPHARM are collaborating with providers of such services to measure the required data to inform payers of the value delivered by an ‘outcomes focused’ approach to community care. The REIMBURSE platform will enable seamless outcomes based contracting for social care, the integration of care delivery and encourage outcomes reporting across key healthcare stakeholders such as care providers, family doctors, hospitals, manufacturers and payers.

3.1.2 Social and community care


Similar to pharmaceutical therapies, Medical device manufacturers often face difficulty in gaining market access with their technologies due to the inherent uncertainty around the limited data available to inform decision making related to access and reimbursement. Due to the advancement of health technology and an increasingly ‘integrated’ approach to care provision, medical devices are becoming increasingly popular instruments to be used in conjunction with conventional interventions and the evidence of their benefits continues to grow. Utilising the REIMBURSE platform will allow manufacturers and payers to explicitly determine the outcomes and true value of such products in a proliferating and competitive landscape; allowing manufacturers to showcase their competitive edge, enabling payers to reduce uncertainty around funding decisions and most importantly providing patients access to technology that improves their quality of life.

3.1.3 Medical devices

3.2 STAKEHOLDER Benefits of using REIMBURSE

Stakeholder benefits of using REIMBURSEFaster access Access to high cost

drugsFacilitates personalised & patient centric healthcare

Pay less for treatment that provide less benefit

Benefit from increased competition between manufacturers

Benefit from accelerated access to innovative therapy

Decreased expenditure on therapies that do not provide value

Allows personalised pricing

Minimise administrative burden & resource use

Remove uncertainty around outcomes and coverage decisions

Automated contracting and patient tracking

Seamless integration to HIS with no disruption to functioning services

Greater benefits for equivalent net monetary spend

Long term reduction in the clinical and economic burden of disease

Ability to provide scalable and consistent quality of care

Ensures data security and privacy

Ability to provide innovative & high cost therapy

Real time overview of uptake & pricing agreements to assist budget monitoring, forecasting and time driven activity based costing (TDABC)

Payers

Patients


Stakeholder benefits of using REIMBURSEReimbursement for high cost therapy

Incentive for innovation

Increased transparency and collaboration with healthcare systems

Minimise administrative burden & resource use

One platform for global performance & uptake monitoring

Privacy for ‘commercial in confidence’ agreements

Expedite approval and reimbursement process

Supports accelerated access

Ability to use same platform globally

Integrated capture of Pharmacovigilance data

Guaranteed and timely transactions

Opportunity to showcase value of products

Ability to provide wider range of therapies

Increased collaboration with manufacturers and payers

The possibility of being rewarded by payers for increasing the value of treatment

Manufacturers

Providers


The REIMBURSE platform has huge potential for uptake, with the possibility of being the premier platform for innovative reimbursement solutions of every drug therapy or medical device that receives regulatory approval and the value based commissioning of wider healthcare provision. There is currently no comparative platform available that can provide automated, scalable and dynamic pricing solutions to facilitate flexible contracting between manufacturers, payers and providers.

As pharmaceutical innovation develops further, it is expected that hundreds of novel agents will be approved over the next 5 years. There are over 7,000 drugs in clinical development across the world, more than ever seen before (PhRMA 2017); with over 450 new clinical trials starting in 2017 alone (Reuters 2017). Experts estimate that of the 7000 drugs in development there are approximately 70% that have the potential to be first in class. Furthermore, individual drugs are being investigated in multiple disease areas to find populations that will benefit from treatment. In some disease areas, combining multiple innovative drugs to support the best possible outcomes for patients is being actively investigated (for example, to treat cancer). With such high levels of innovation poised to deliver unparalleled benefits for patients, healthcare systems and manufacturers will need to work together to agree suitable innovative pricing solutions.

Cancer drugs have been the most researched in recent years and are driving the growth in the pharmaceutical drugs pipeline. This poses a considerable challenge as these drugs often bring with them a high price tag that accounts for the benefits they bring. The cost of patented cancer drugs in the US alone have increased by 5-10 fold since the turn of the century, with the average cost of drug therapy being around $100,000 per year with patients commonly responsible for 20-30% as co-payments (Kantarijan et al 2014). High prices for innovative therapy that may or may not work can result in patients refusing treatment or selecting less optimal treatment plans due to the financial difficulties they may incur (Zafar et al 2013). In the US, leading payers namely UnitedHealth group, Aetna and Anthem have nearly reached their current target of 50% of total annual healthcare spend through value-based care and simple ‘pay for performance’ agreements (Forbes 2017). Aetna seek to lead the industry with a target of 75% value-based expenditure model by 2020, as they hope to build on their current initiatives to improve quality of care and lower costs at the same time (Forbes 2017; Bach & Pearson 2015).

Therefore, the potential of the REIMBURSE platform is tremendous as it will be able to support smart contracts for both new and existing treatments as healthcare systems across the globe continue pushing the transformation to value-based care.

3.3 Market size

Pharmaceuticals


Sustained increases in rates of chronic disease, communicable diseases and life expectancy result in continuous demands for financial resources to control the ever-expanding burden on global health systems and societies. Global health expenditure is expected to reach estimated to be $8.7 trillion USD by 2020 and the proportion of GDP spent on healthcare will rise 10.5% (Deloitte 2017). The trend towards value-based healthcare, is being witnessed by widespread reform to healthcare policies and programs in order to reduce costs and maximise benefits for patients.

According to a recent study, the global medical device market reached more than $500 billion USD in 2017 and will continue to grow beyond $650 billion USD by 2022 (Medical Devices 2018). Increased competition in this highly innovative market segment combined with funding constraints for health systems will result in an increased utilisation of outcomes-based pricing agreements across the globe to enable sustainable patient access to the best available technologies and instruments. As health systems across the globe continue pushing the transformation to value-based healthcare, the potential of the REIMBURSE platform is tremendous as it will support smart reimbursement contracts for both new and existing healthcare interventions across a wide range of market sectors.

Healthcare provision and social/community care

Medical devices


4. INSIGHTS & DIGIHEALTH

Real world evidence (RWE) is defined as any evidence that is derived from clinical settings in regards to the outcomes associated with the provision of a therapy in a day-to-day context beyond clinical research studies and not collected in conventional randomised clinical trials, i.e. safety reporting, claims data, patient reported outcomes or efficacy data. RWE or real world data (RWD) is playing an increasingly valuable role in the following areas:

» Informing reimbursement and coverage decisions by payers or regulatory agencies

» Identifying patient groups or disease areas with high unmet medical need

» The development of HTA dossiers by manufacturers and pharmacoeconomic

evaluation of healthcare technology or programmes, for example, in health economic

modelling it is used to inform the validity of parametric survival extrapolations.

» Supporting clinical guidelines and the development of decision support tools in clinical

practice including the tracking of patient outcomes and safety data

» Informing clinical trial design

» Pharmaceutical companies and health insurance providers spend vast amounts of

money on the latest patient level data to inform business planning, identify unmet

needs and develop product strategy

» The performance of effectiveness studies to remedy the limitations of randomised

clinical trials such as homogenous patient groups, recruitment bias, external validity

and generalisability

4.1 What is Real world evidence?


Despite the increased reliance on real world data (RWD) to inform health related research, challenges relating to the collection, distribution and availability of this data continue to exist. Failure of pharmaceutical companies to develop responsive and capable RWE-based systems means that they carry the risk of losing control of value communication associated with their therapy. While health insurance providers currently have access to considerable amounts of data that is derived from clinical settings, much of this data is retrospective data (e.g. claims data). The use of static data to inform forecasting, trend analysis and business planning and the length of time taken to gain access to such data results in limited forecasting choices and risk of oversight with regards to current developments in an increasingly dynamic industry such as healthcare. Some of the current limitations of observational RWD include:

» Lengthy delay in availability of outputs

» High cost and resource use required to generate or collect observational data

» Inconsistency and incompatibility of data arising from numerous sources

» Disparities in formatting methodologies between data collection centres

» Concerns over the privacy and security of patient data

» Fragmented data from a variety of sources that is time consuming to amalgamate

and present in a consistent manner

» Absence of potentially useful information and lack of access to data for patients

» Lack of incentives for patients to contribute data

4.2 Current challenges


The INSIGHTS platform will extract anonymised patient level data from the REIMBURSE platform and electronic patient records to the world’s first ‘live’ real-world evidence (RWE) database, that is accessible by subscribed users at real time (Figure 5). Uniform and standardised inputs to smart contracts which are encapsulated within the REIMBURSE platform and the architecture of DIGIPHARMs’ bespoke integration solutions to health information systems promptly address several of the limitations that are observed with conventional RWD collection and database generation, thus expediting the time to availability of consistent and ‘ready to use’ RWE outputs. Additional health related data such as genomic data will also be linked to the INSIGHTS platform in partnership with leading evidence providers in the industry, to create an unparalleled health data marketplace in preparation for a value-based, data-driven future of healthcare. The use of cryptographically encrypted blockchain technology also eliminates all patient privacy and data security concerns that affect current RWE generation systems. There are no such ‘live’ RWE databases currently available.

4.3 INSIGHTS, why wait?

Figure 5. The INSIGHTS ecosystem


INSIGHTS will be one of the key solutions to informing and validating performance of therapies that have been approved under accelerated access initiatives and will also strengthen the capacity of healthcare systems to conduct pragmatic or nested clinical trials. The INSIGHTS platform will also feature an automated publication trawler to provide users with the the ability to access the latest scientific publications relevant to the users data request. Furthermore, DIGIPHARM is developing in-built data analytics using statistical algorithms, artificial intelIigence and machine learning methods that will be integrated to the INSIGHTS platform and conducting in-house analyses with the assistance of our partners and strategic collaboration with relevant stakeholders.

The availability of ‘live’ RWE will provide payers, manufacturers and providers with ‘real time intelligence’ with which they can inform strategic decisions, product development and anticipate treatment pathways. The generation of tangible, timely and consistent data at a fraction of current costs with no delay, will encourage the increased utilisation of RWE and eliminate the reluctance of all stakeholders from accessing such data. As health insurers move away from a business planning approach towards a flexible data-driven iterative approach, the ability to test, model and receive feedback from a live intelligence source within a landscape that is progressing to personalised medicine could prove to be invaluable. Real time performance metrics from clinical, economic and safety perspectives would be desirable to all stakeholders and can help improve the quality of patient care.

Key features

Greater data usage results in greater patient rewards

Greater rewards for data related to rare disease

GDPR compliance - patients are in control of their data

Complimentary genomic profiling for data contributors

Global health data


Patients registered on the DIGIHEALTH application will have the ability to opt-in to a clinical trial recruitment portal where according to their personal characteristics they will be permitted to either apply to relevant trials or be contacted directly by research organisations. Patients will also be able to register to a portal dedicated to patient insights where they have the option to anonymously take part in healthcare related questionnaires and surveys or contribute to patient reported outcomes studies in return for a reward from research organisations.

Clinical trial recruitment and health research portal

DIGIPHARM is a strong believer in empowering patients with the custodianship and ownership of their personal data. Patients will be incentivised and rewarded for sharing and contributing their health related data to populate the INSIGHTS and DIGIHEALTH platforms, if they so choose. Patients who contribute their data to these platforms will be granted complimentary access to the relevant platforms as a source of invaluable medical information. Using digital identifiers to tag contributor data, patients will be rewarded every time their data is accessed or utilised to generate RWE using smart contracts. Patients who contribute ‘digital nuggets’ of valuable data such as those for rare diseases will be provided with increased rewards to reflect the market value of such information. DIGIPHARM in tandem with partner organisations is exploring optimal mechanisms of incentivising patients for their data contribution, subject to regulatory and legal considerations.

4.5 Patient rewards and patient empowerment

The DIGIHEALTH platform will utilise data from the INSIGHTS database to generate a patient-friendly portal for sharing and utilising health-related information on a global scale for the benefit of fellow patients, wider society and health systems worldwide.

As health literacy among patients is increasing, and with approximately eight out of ten internet users having searched for medical information online (Manganello et al 2017); there is great need for an increasingly informative, high quality and up-to-date evidence source that patients may access. The DIGIHEALTH platform would be an important source of supporting evidence for patients who wish to enquire about the real world benefits of treatment options available to them and would provide patients with valuable information in regards to the recent outcomes or prognosis of patients with similar characteristics to themselves. Patients will also be able to access data comparing outcomes from different treatment centres to help them to identify the best possible care providers. Data of comparable quality is currently out of reach to patients and typically too expensive to access, resulting in the retrieval of health information from outdated or non-accredited sources. Easily accessible patient information leaflets will also be available directly on the DIGIHEALTH platform. DIGIPHARM seek to empower patients with the knowledge they require as the healthcare horizon becomes increasingly patient centric.

4.4 DIGIHEALTH

Informing patients


4.6 Benefits of the INSIGHTS & DIGIHEALTH platforms

Stakeholder benefits of the INSIGHTS & DIGIHEALTH platforms

Incentives for data contribution

Benefit from evidence based care

Facilitates personalised & patient centric healthcare

Security and privacy of data transfer

Ability to access up-to-date and reliable health information

Custodianship and ownership of their own data

Real time overview of patient outcomes to inform decision making and guidelines

‘Full spectrum’ RWE e.g. access to live consumption data to inform revenue analytics and health resource allocation

Eliminate resource use and costs of setting up patient registries with no patient tracking requirements

Cryptographic encryption ensures data security and privacy

Ability to anticipate and account for health related trends in real time

Seamless integration to HIS with no disruption to functioning services

Informing HTA process and payer negotiation

Aid value-based healthcare delivery

Faster Identification of areas with high unmet need

Patients

Payers

Key features

View real life health outcomes based on personal characteristics

View health outcomes categorised by health institution

Ability to participate in surveys and questionnaires for rewards

Enables clinical research organisations to identify and contact patients of interest

Help patients identify treatment centres that provide the best outcomes

Access digital patient information leaflets

Platform for reporting ‘Patient Reported Outcome Measures’


Stakeholder benefits of the INSIGHTS & DIGIHEALTH platforms

One platform to receive global insights

Reduce the need for lengthy and expensive observational studies

Valuable data to inform HTA submissions and payer negotiations

Access to RWE without delay, at any time

Ability to conduct pragmatic clinical trials cheaply and efficiently

Pivotal evidence to inform early clinical study design, de-risk trial execution and insight to therapy patterns

Significant cost savings compared to purchasing data from conventional ources

Bypass organisational and regulatory barriers to facilitate RWE collection

Ability to provide an integrated analysis of costs and outcomes in combination with REIMBURSE

Inform evidence based medical practice using real time data that is continually updated

The ability to provide greater quality of care under the umbrella of a value-based delivery system

No additional burden at clinical level compared to active participation in RWE studies

HIS = Health Information Systems; HTA = health technology assessment; RWE = real world evidence

Manufacturers

Providers

4.7 Market sizeThe use and reliance on RWE is growing and will have huge impact in supporting clinical research, trial execution and decision making in healthcare. There is a clear need for the provision of timely and readily accessible RWD to inform industry, policy makers, providers and payers of product performance. Regulatory bodies and HTA agencies are fully supportive of its use. Pharmaceutical companies and health insurers regularly purchase aggregates of RWD or sponsor RWE studies for substantial amounts of money, often collecting data that is not required or valuable resulting in a waste of resources. The demand for robust and timely RWD shall only increase as payers and regulatory agencies seek to inform and review their decisions to approve novel therapies based on less evidence as seen with the FDA’s accelerated approval program. The INSIGHTS platform will provide patients with access to an unparalleled health information portal which cannot be matched by any other source today.

From a global health policy standpoint, 80% of low to middle income countries do not have the necessary data to drive cancer policy for decision making and resource planning (IARC 2017). INSIGHTS allows stakeholders in emerging markets without the resources to conduct observational studies or manufacturers who do not deem typical evidence generation methods to be cost-effective in these localities, to still have access to robust RWE at significantly reduced costs and without delay.


The future projects outlined in section 5 represent platforms for the future. Their implementation is strongly dependent on permissibility under applicable laws.

5. Pipeline projects

There is a growing body of research demonstrating the benefits of financial incentives for patients in healthcare. Despite the strong evidence showing that incentives for patients with chronic diseases result in improved health outcomes, the act of incentivising patients with their healthcare management it is extremely underutilised. Studies have concluded that even relatively small incentives can influence health-related behaviours significantly (Volpp et al. 2009). Furthermore, the implementations of such plans have demonstrated favourable cost effectiveness results in cohorts of patients who have received incentives (Giuffrida and Troxel, 1997). Proven cost effectiveness of such initiatives is an early indicator that the inclusion of incentives for patients is likely to be implemented in health systems around world as the industry is increasingly focusing on providing value-based healthcare and seeking to engage directly with patients in order to optimise outcomes. Incentivising patients will also be crucial in the application of performance-based pricing of pharmaceutical products for chronic diseases. In order for patients to receive optimal benefits from regular medication that is administered at home, incentives for patients help address concerns regarding adherence and compliance. The FDA have recently approved a groundbreaking ‘digital pill’ which is able to signal when a dose has been taken via embedded sensors thus opening a realm of possibilities in adherence tracking (FDA 2017).

5.1 MYHEALTH - incentivising patients for superior outcomes

In collaboration with healthcare providers and payers, patients will be tracked by the MYHEALTH application and will be incentivised according to their health-related behaviour, adherence and compliance. With the current growth in data generation for health related behaviour, such data will be utilised in tandem with health insurance providers to provide incentives to patients. Data collection on the MYHEALTH platform will allow health insurance providers to identify lower risk patients and offer subsequent reductions in health insurance premiums. DIGIPHARM is working with subject matter experts to assess the feasibility of incentivising patients in numerous areas as such as the collection of health-related quality of life data, attendance to medicine use reviews and the elimination of drug wastage in community pharmacy practice, public health initiatives like needle exchange schemes, and continued attendance to outpatient physiotherapy appointments following surgical interventions. DIGIPHARM will be aiming to conduct numerous economic evaluations to across many disease areas to identify where incentives will provide optimal value for health systems and will determine the appropriate mechanisms for the implementation of patient incentives while conforming to financial, legal and regulatory standards.


Ensuring funds are consistently available for research and development activities for some manufacturers is becoming increasingly difficult due to reductions in the long term profitability of newly launched drugs as a result of shortened exclusivity, biosimilar threat, smaller eligible patient populations for targeted therapies and the competitive landscape of drugs targeting the same disease area. Manufacturers are also less likely to commit resources to the development of orphan drugs for rare diseases, where patient populations are so small that the economic incentives to develop novel therapies are low. Regulatory bodies or charities are often required to incentivise pharmaceutical companies to commit resources to the research and development stages for orphan drugs to increase the possibility of generating sufficient returns on their investment with products that suffer from relatively high attrition rates.

DIGIPHARM intends to propose new methods for crowdfunding medical innovation on the EVOLVE platform, to enable fundraising via initial exchange offering (IEO) and digital assetization to support early proof-of-concept research, ex-vivo studies and pre-clinical studies. The EVOLVE platform is likely to become a valuable addition to early funding phases in drug development and health related innovation. Taking into consideration possible declines of manufacturer revenue in the coming years, innovate fund raising programs will provide a unique opportunity for individuals to contribute to the sustainable development of the health sector and the opportunity for manufacturers to acquire these novel products once they are convinced that these technologies show positive results at the pre-clinical development phase.

The EVOLVE platform will also offer crowdfunding solutions for wider health related innovation, for example the development of medical devices and digital health products. Early stage researchers are often required to spend lengthy amounts of time preparing grant proposals and engaging with venture capital enterprises providing an unwelcome distraction from focusing the majority of their resources towards product development.

5.2 EVOLVE - supporting innovation in health


6. Technological considerations

In anticipation of the challenges presented by integrating DIGIPHARMs’ platforms with existing IT infrastructure within national health systems or large primary care networks, agile API integration studies of such diverse and complex systems will be performed prior to the development of our integration engine. Where API integration with existing infrastructure is neither feasible or applicable; for example independent clinics, standalone applications will be developed. Our team is dedicated to facilitating the timely uptake of DIGIPHARMs’ solutions in real world settings and to help potential users embrace our platforms whilst minimising any adverse impact on existing infrastructure. Leveraging on an API driven development process will allow the development of user friendly interface to allow users to simply invoke smart contract transactions or query ledger data when required.

Since much of data transferred on DIGIPHARM platforms is likely to be confidential for many platform participants, using permissioned blockchain technology will give members the power to conduct confidential transactions using private channels. For example, this would allow the safeguarding of confidential pricing information between manufacturers and payers (member peer nodes) where subjects can only join such channels subject to approval by all channel members. DIGIPHARMs’ fully independent platforms will all utilise confidentiality domains to conduct private data transactions over secure, cryptographically encrypted channels. Additionally, such technology can also allow global entities to operate local peers in multiple regions while still being part of the same blockchain network.

Our development team will also be focusing heavily on interoperability between alternative blockchain platforms, utilising an approach similar to ChainLink, allowing for integration of not only other blockchains, but Web APIs. As anticipated, the increased adoption of blockchain technology in the health industry e.g. decentralised medical records or payment systems, will require DIGIPHARM platforms to support such eventualities.

6.1 Overview

The successful integration and development of the DIGIPHARM ecosystem will enable the possibility for health related decentralised applications to be affixed as application layers on the DIGIPHARM platform. There are also possibilities to be create a layover platform for existing health information systems to connect siloed healthcare stakeholders, allowing them to easily share data that is critical to healthcare such as electronic health records.

6.2 Potential for further development


DIGIPHARM aims to establishing physical and technical safeguards as well as technical policies to ensuring the transmission of data securely over networks. DIGIPHARM are proactively building internal business processes to adhere with the following:

» Health Insurance Portability and Accountability Act of 1996 (HIPAA)

» Federal Trade Commission Act 1914 (FTC)

» Health Information Technology for Economic and Clinical Health Act of 2009 (HITECH).

» ISO 27001

» Caldicott principles

» Health Information Trust Alliance (HITRUST) CSF certification

» The General Data Protection Regulation (GDPR) (Regulation (EU) 2016/679)

» NIST cybersecurity framework

» local and regional data protection acts where applicable

» International privacy by design prinicipals (PbD) as defined by the the International

Association of Privacy Professionals

» ICHQ10 quality by design principals (GxP regulated environments)

» GAMP 5 computerised validation concepts (GxP regulated environments)

» ‘By design’ compliance program covering Security, Privacy and Quality.

6.3 Compliance, regulatory considerations and information governance


Our priority is ensuring the confidentiality, integrity and availability of data during collection, storage and analysis phases.

6.4 Cyber Security Strategy

Using a blockchain is not enough for what DIGIPHARM wants to offer to its users. Public blockchains inherently lack privacy and confidentiality functions which are critical when it comes to sensitive patient data and commercial pricing agreements between various parties.

Private Blockchain Security for Healthcare Services

Figure 6. Contract confidentiality (IBM)


All software development at DIGIPHARM follows the Secure Development Lifecycle. DIGIPHARM enforce compliance with industry best practices at all stages of development and code is tested for vulnerabilities before it is shipped to production. Security is an integral part of development at all its seven stages:

1. Training DIGIPHARM provide secure development guidelines to developers on joining the team. They are made aware of the business requirements for privacy, non-repudiation, confidentiality and availability.

2. Requirements The requirement for security is injected at the strategic level of planning of any functional element in the code. Security bugs are solved to the maximum degree possible during development and these standards apply throughout th e duration of the project.

3. Design The potential attack surface is analysed in advance to building the product. The design of functionality takes into account the potential risks in processes and technology.

4. Implementation Approved tools in their latest versions will be used. Unsafe functions are banned from the outset to reduce the potential attack surface. Source code scanning tools to check the code for vulnerabilities before it’s compilation will also be used.

5. VerificationRun-time verification checks are performed along with fuzz testing to reveal potential security issues prior to release.

6. Release DIGIPHARMs’ Incident Response plan helps to address security issues after release of the software. The Final Security Review (FSR) will include the examination of threat models, tools outputs, and performance against the quality gates and bug bars defined during the Requirements Phase.

7. Response DIGIPHARM take any report of potential vulnerabilities seriously. A bug bounty program will reward researchers for security bugs found before they are found by adversaries, preventing exploitation at a very early stage.

Development

DIGIPHARM provides entities with competing business interests the ability to coexist and transact while maintaining the privacy and confidentiality of their own sensitive contracts. Specific subsets of network members can use channels to communicate privately.

Privacy and Confidentiality


DIGIPHARMs will host its infrastructure in secure cloud environments with rigorous monitoring, patching and hardening in place. Prior to deploying any infrastructure element, hardening will be rigorously applied to software configuration and passed through a checklist of security requirements. Whenever possible, DIGIPHARM will use enterprise cloud providers which will provide preconfigured, secure infrastructure that satisfy local and regional requirements.

Infrastructure

DIGIPHARM networks and endpoints will be constantly monitored for security anomalies and initiate dedicated investigation protocols whenever suspicious activity is identified.

Security maintenance

Utilising the Ethereum ecosystem for interoperability and the incorporation of ERC20 compliant tokens offers the ability to process transactions and interact with smart contracts from other blockchains, making it ideal for integration with additional networks. Several blockchain projects and decentralized application platforms are in existence, with more under development that are compatible with the Ethereum blockchain. This offers a wide range of benefits for future development, most notably, the possibility of blockchain agnostic access to the DIGIPHARM platform and services. DIGIPHARM modules will be designed with cross-platform and inter-blockchain compatibility in mind, in anticipation of strategic partnerships and interaction with decentralised health related platforms currently under development.

6.5 Benefits of using the Ethereum ecosystem


Private blockchain technology has many benefits to its use when dealing with healthcare and other personal related data. When considering the best architecture to build a secure and scalable solution, private blockchain technology is the best solution for the below reasons:

DIGIPHARM’s Reimburse platform uses Smart Contracts to capture the results of the negotiations between contracting parties and key health care stakeholders over a permissioned, multi-channel Hyper ledger Fabric network (v1.1). The Blockchain network will integrate with a Data Lake, which connects and collects data from multiple, diverse data sources to satisfy and inform any conditions attributed to an outcomes-based pricing agreement. This includes the ability to accommodate any settlement or periodicity requirements and support varying levels of aggregation. The platform uses standard Fast Healthcare Interoperability Resources (FHIR) (https://www.hl7.org/fhir/overview.html as a reference, the latest standard to be developed by the HL7 organisation.

As part of the business model, DIGIPHARM will recruit and incentivise patients to store Real World Data (RWD) in DIGIPHARM’s Data Lake (DDL). Enabling mechanisms to collect, process, aggregate and provide data within the architecture of the Insights platform. Insights will be connected to a powerful statistical engine, based on R (https://www.r-project.org/about.html) to produce standard analyses and output Real World Evidence (RWE) for health related-research or enable access to raw data for research organisations to conduct custom or tailored analyses.

• Security – Private, permissioned blockchains are built around security. Both their permissioned architecture and its use of private channels and encrypted chip level technology make them ideal for the processing and transmission of confidential information.

• Confidentiality - Typical blockchain networks do not support truly private transactions and confidential contracts, as peers on the blockchain have access to all information that is broadcast. Peers on private chains can be decoupled into distinct roles. Confidential information can be broadcast to specific peers with the proper permissions on the network to maintain complete confidentiality. Such a system is crucial when dealing with confidential access agreements between transacting parties.

• Scalability – Permissioned blockchains that require every peer to execute every transaction, maintain a ledger and run consensus have proven difficult to scale at an enterprise level. Private architectures are designed to be modular and scalable. Nodes are given specific roles so that resources can be dynamically added to maintain network performance and scale without typical limitations.

• Smart Contract Execution – Utilising private blockchains, permission based smart contracts can be executed on the network, facilitating interaction between nodes on secure channels.

6.6 Benefits of using Private Blockchain Technology

6.7 Functional architecture summary


A strict, sophisticated and complex service for anonymisation of records is performed at the lowest level of data collection. The platform will abide to GDPR and HIPAA regulations within the legal requirements and boundaries of sensitive data collection and processing. DIGIPHARM use permanent mechanisms to trace data usage across all the platforms within the network with two main intentions: to record usage, compliance and maintain traceability. These mechanisms are imperative to support the continuous incentivisation programs offered to patients and service providers where applicable.The DIGIPHARM network will be fueled by a ERC20 Ethereum minted token (DPH), which is used as a mechanism to monetise transactions and incentivise participants.

The following diagram and table describe the overall architectural and integration process steps across the Reimburse and the Insights applications (Figure 7). Fundamentally, Reimburse functions by creating a smart contract over a Hyperledger network between transacting parties, one serving as provider of goods or services and the other contracting party as the payer or consumer of such goods or services. Supplementary nodes within the network are made available to integrate with the DDL or relevant data sources when required.

Architectural process

Figure 7. Architectural process


A step-by-step illustration of the activities and actors within the functional architecture of the DIGIPHARM network is provided below (Figure 8).

Functional Architecture

Figure 8. DIGIPHARM network functional architecture


On the Reimburse platform, smart contracts are utilised to digitalise, facilitate & automate innovative-pricing agreements, no matter how complex with minimal administrative burden. Information attributable to whether a metric, outcome or level of performance was achieved (or not) will be automatically processed in the smart contract with automatic reconciliation. The information feeding this smart contract can come from various source systems (registries, health information systems, medical devices, health apps, etc.)

Smart Contracts

6.8 Reimburse Platform functionality

Due to the nature of both the confidential pricing agreements between stakeholders and sensitive patient data, secure channels on the DIGIPHARM private blockchain network will be utilised to transmit sensitive information and to meet all compliance, regulatory and data protection laws. A trusted & private network for entities participating in value-based agreements is built on Hyperledger Fabric v1.1

Entities can be providers, payers, manufacturers, and even patients. Only participants that are accepted by others can join the network. Because all parties are recording all transactions, everyone in the network has the same understanding and data integrity is guaranteed. If a party wants to change information, the other participants in the network have to confirm the changes – and this change will be recorded on the Blockchain. As with any other permissioned network, it will be ruled by its constitution where participants abide to follow the conditions and terms of the engagement. These characteristics are critical to the development of a medical information infrastructure that will enable the reimbursement of healthcare and health technologies according to real-world patient outcomes and benefits, eliminating counter-party risk and creating trust around the data used to inform reimbursement.

Distributed Ledger


In the scope of the current architecture, Reimburse has been developed with all-inclusive flexibility in order to function within the wide variation of global health economies and reimbursement systems (Figures 9-12).

Example use cases

Figure 9. Single Payer – National registry – Integrated HCP

Figure 10. Multi-payer – Integrated HCP


Figure 11. Multi-payer/Individualised medicine – Out pocket/Co-payment – Distributed HCP

Figure 12. Value-based multi payer/individual medicine including logistics distribution


DIGIPHARM’s Data Lake (DDL) utilises a combination of the latest technologies to perform speedy, flexible, accurate and meaningful queries across a multitude of data structures using SQL and non-SQL techniques to retrieve the necessary information for multiple purposes.

To fulfil the functionality of the Reimburse platform and smart contract requirements

» As a data source, storage repository and “feeding engine” for the evidence generation

and health data exchange

» To automatically construct, and or derive, metadata to facilitate querying and analyses

across different sources.

Smart Contracts

6.9 DIGIPHARM Data Lake

The DDL is a trusted, secure and private data lake that has incorporated numerous integration engines; those that are standardised (e.g. HL7, DICOM…), those that do not follow any specific standards (custom), those that have been optimised internally (bespoke) and those that have been developed by non-healthcare providers but are envisaged to be of benefit within the scope of DIGIPHARM’s commercial activities. The integration systems on DIGIPHARMs’ platforms will be based on the most recent standards for health record standardisation, disease coding and outcomes recording. All of these standard systems have been selected due to the intrinsic and collaborative working approach of their respective developing organisations, and the ability for DIGIPHARM to construct and facilitate content, contextualise data sources for analysis and dynamically update to newer releases of these standards when deployed.

The DDL will perform data collection activities, mapping, transformation, curation, cleansing and connection to the Reimburse platform via a subset of the smart contract defined during the early stages of the engagement (see smart contract above). This connectivity will be achieved by the integration of the smart contracts, the blockchain and the DDL; making it a unique feature integration where these technologies collaborate in an orchestrated fashion to achieve efficient, transparent, immutable, trustable and decentralised data management. Additionally, the DDL will be used as repository for patient electronic health and medical records (EHR/EMR), as a basis for conducting RWE analytics and enabling the functionality of DIGIPHARMs health data exchange.


A secure and trusted application that connects to the DDL and the Reimburse platform, allowing users to contribute health related data to be used for clinical research, personalised outcomes research, and provide research opportunities for key healthcare stakeholders (Figure 13).

Users are able to receive rewards for participating in health-related surveys and questionnaires. Patients will also be rewarded if they choose to contribute data to the system and will receive further rewards each time their data is used by healthcare stakeholders to inform research activities. Patients who enter outcomes-based pricing agreements with healthcare stakeholders directly are also able to monitor the current state of their contractual agreements or directly inform such agreements where patient reported outcomes are required.

Digihealth will interact directly with the DDL to allow for the contribution of health data, and for it to be queried by users based on a number of specific factors. Each time a user interacts with the DDL, those actions are tied to their digital Identity on the network and used to provide a record of their actions, to facilitate rewards for the contribution and monitor data access by a third party.

Smart Contracts

6.10 Digihealth

Figure 13. Digihealth network functionality


The secure and decentralised mechanism to manage identity and data usage within the DIGIPHARM network is built on top of HyperLedger Indy and will interact with all parts of the DIGIPHARM platform. HyperLedger Indy is a distributed ledger, purpose-built for decentralised identity. It provides tools, libraries, and reusable components for creating and using independent digital identities rooted on blockchain or other distributed ledgers so that they are interoperable across administrative domains, applications, and any other ‘silo’. The identities created are private, secure and trusted by design.

In keeping with the DIGIPHARM vision of giving the patient full control over their data, DIGIPHARM utilise decentralised identity protocols to empower users to control and manage their identity, thus controlling all access to their data. This allows for GDPR compliance, as a fully transparent download of how data is being used is now possible and the revocation of access to some (or all) of that data will be in the direct control of the user.

By eliminating a centralised authority’s control over a user’s identity, DIGIPHARM will provide the patient true visibility into how their data is being used. This provides granular control over who can access this data, the purposes it is being used for and the duration of data access. Full portability of this data will also be possible should they wish to share this data with other parties or platforms. DIGIPHARM will deploy and manage a network of trusted nodes used to facilitate decentralised identity services and allow users to interact with all parts of the platform anonymously and securely. A single, secure identity will allow for the cohesive operation of services and products, and for rewards to be distributed to the user’s wallet seamlessly.

6.11 Decentralised Identity Services

To facilitate payment for the use of the DIGIPHARM products and services on the platform, each user identity will be linked to an ERC20 based wallet address. Each time a service is utilised on the DIGIPHARM platform, a user will initiate a transfer of DPH tokens to a designated wallet address owned by DIGIPHARM. Once tokens are received, an API key to access the service or information on the platform will be issued. This API key will deliver a specific set of data to the user, or timed access to a specific set of data. The DIGIPHARM wallet will also allow for impending features to be implemented such as; automated payments, peer-to-peer information exchange, patient rewards and interaction with pricing agreements for stakeholders. The DIGIPHARM wallet will integrate with the platform allowing for seamless payments and value transfer across all products.

6.12 DIGIPHARM Wallet


Analytics HubA powerful statistical engine based on R (r-project.org) that will enable advanced, complex and predictive analytics to understand and produce Real World Evidence. This platform will enable collection, visualisation, analytics, management and sharing of information across the different parties.

Phone Apps & IoTAs per design, the patient is at the center of DIGIPHARM’s efforts and technology. The DIGIPHARM network allows interaction with patient tools or IoT (Internet of Things) enabled devices, supporting medical device communication standards like CEN ISO/IEEE 11073, HL7 and the soon to be released NIST for outcome collection, remote monitoring, quality of life questionnaires or general inputs, control, adherence, support and guidance among others.

Sub-chains or Temporary chainsA revised and innovative use of the Hyperledger Blockchain that will enable a full trace for patient data across the trusted network, created on a temporary basis to serve the following purposes:

» Supporting smart contracts - as data is collected and shared across different entities,

these chains will be made available for the duration of a contract, but once its purpose

is fulfilled, they are removed from the network.

» Supporting patient records utilization – where data is provided by patients (with

consent), the use of their data and subsequent rewards must be transparent and

trusted throughout its life cycle; until either the consent is revoked or any other

conditions change.

» Data protection and data privacy

6.13 Additional features across platforms

Patient incentivesExecuted via ERC20 tokens, a wallet and a fully integrated data chain; patients can securely share their EHR/EMR and relevant clinical data where applicable. In order to achieve full transparency and facilitate seamless incentivisation mechanisms, DIGIPHARM will make use of the following features:

» DDL – a cloud base solution for patients to freely, securely store and retrieve their data

as in needed basis.

» Decentralised Identity Management – full trace of when and how the patient identity

or data is in use, providing e-consent features to provide the autonomy and control

that is expected.


8. DPH health economy

The DIGIPHARM platforms will be built to support all stakeholders seamlessly, utilising task automation via smart contracts wherever possible. It will be architected with security, data protection and regulatory compliance at the forefront of the design.

The health economy will involve the following participants:

» Patients

» Payers

» Manufacturers

» Providers

» DIGIPHARM Platforms

8.1 Health economy stakeholders

» Integration support

» Toolkit for payers, providers, manufacturers and private insurers

» Strategic pricing review and strategic advice

» Reimbursement process review and collaboration with payers/providers

» Process review for clinical and industrial clients - automation and digitisation of health

services

» Health economic modelling and forecasting

» Advanced data analytics

7. Additional services


DIGIPHARMs’ platforms are a decentralised public/private blockchain based solution that enables the delivery of value-based pricing agreements to stakeholders and securely gathers and stores real world evidence from patient data. It enables the delivery of personalised healthcare solutions.

DIGIPHARM Platform Features:

» Smart contracts for innovative pricing agreements and task automation

» Patient website and app

» Interface for Manufacturers/Payers/Providers

» Integration into existing stakeholder I.T. infrastructure

» Legal/Regulatory/Compliance mechanisms

Platforms

Manufacturers are typically pharmaceutical companies or medical device companies that produce and distribute health technologies.

Manufacturers will:

» Participate in innovative pricing agreements

» Outline/Agree to innovative pricing agreements via the REIMBURSE user interface

» Purchase access to the INSIGHTS database

» Receive automated payments, subject to regulatory and legal considerations

» Incentivise patients to contribute to health related research via DIGIHEALTH

Manufacturers

Patients will:

» Provide permission to share data if they choose to participate

» Receive incentives to contributing their data in the form of

access to valuable health information

» Receive rewards and incentives for contributing to health

related research via the DIGIHEALTH application

Patients are the focal point of the DPH health economy. Not only will patients receive the benefits of a value-based healthcare approach, but if they so choose, they will be incentivised for contributing personal health related data to the INSIGHTS database for further use in health-related research.

Patients


Providers are hospital networks, clinicians, healthcare professionals etc.

Providers will:

» Continue to measure and record clinical outcomes on existing local systems

» Not be required to individually enroll patients to DIGIPHARM platforms

» Participate in personalised value-based pricing agreements directly with

manufacturers (private healthcare)

» Receive automated payments (where applicable), subject to regulatory and legal

considerations

» Receive incentives from healthcare systems to ensure accurate and timely

completion of outcomes data within patient records


Providers

Payers are government entities or insurance providers that reimburse manufacturers or where relevant, healthcare providers within the DIGIPHARM health economy.

Payers will:

» Participate in value-based pricing agreements

» Outline/Agree to value-based pricing agreements via the REIMBURSE user interface

» Participate in automated payment mechanisms, subject to regulatory and legal

considerations


» Incentivise patients to contribute to health related research via DIGIHEALTH

Payers


Blockchain is a distributed database technology, most recognized for being the backbone of digital currency platforms such as the Bitcoin and Ethereum networks.

Smart contracts are self-executing pieces of code that digitally facilitate, verify or enforce the terms of a predetermined agreement. These contracts allow transactions to be carried out between parties anonymously with no need for external enforcement or action. All transactions based on smart contracts are published to the blockchains ledger and provide both transparency and immutability. Blockchain technology is utilised to provide the below services within the DPH health economy:

8.2 Blockchain technology & smart contract application

» Smart contracts

» Private Channels

» Digital Identity Services

Smart contracts will be used to facilitate innovative pricing agreements between manufacturers and payers, and potentially providers depending on the clinical setting.

Due to the nature of both the confidential pricing agreements between stakeholders and sensitive patient data, secure channels on the DIGIPHARM private blockchain will be utilised to transmit sensitive information and to meet all compliance, regulatory and data protection laws.

Digital identity services provided by the blockchain will be utilised to create profiles for enrolled patients and other stakeholders while maintaining anonymity within each platform.

Smart Contracts

Private channels on a fully independent platform

Digital identity services

9. DIGIPHARM tokens (DPH)

DIGIPHARM (DPH) tokens will be used to pay license/access fees on DIGIPHARM platforms. Access fees will invariably be determined and stipulated in USD value and the quantity of tokens required will depend on the type of access (manufacturer, patient, payer or provider) combined with the form of interaction required. The quantity of tokens required for such interactions is subject to change, relative to the market value of DPH.

9.1 DPH token use


DPH tokens can be used where required to incentivise and reward network participants.

REIMBURSE:DPH tokens can be used where required to incentivise and reward network participants. DPH tokens will be used to incentivise and reward patients who share their health data with the network.

INSIGHTS:

DPH tokens will be used for access rights to the DIGIHEALTH platform. Research organisations will require DPH tokens when constructing and generating patient-relevant studies on the platform.

DIGIHEALTH: DPH tokens will be used by healthcare institutions to enrol patients onto the MyHealth platform and required for specific data requests by research organisations.

MYHEALTH:

DPH tokens will be used for access rights to the EVOLVE platform. DPH tokens will also be required to access comprehensive data and reviews related to advertised health technologies and projects.

EVOLVE:


» DPH Supply: 100,000,000 Fixed (ERC-20)

» Ticker code: DPH

» Decimal Places: 18

9.2 DPH token characteristics

Figure 14. DIGIPHARM Token economics

» DIGIPHARM reduces DPH supply on the free market by purchasing tokens on behalf of

industrial clients for platform/network utilisation

» There will be ‘minimum and perennial’ DPH token holding requirements for Reimburse

network users to maintain token demand

» High transaction volumes for value-based contracting

» Vesting periods of 6-24 months for team, board and partners

» Tokens used on the platform will be held in a DPH service wallet for 3 years from time

of utilisation

9.3 DIGIPHARM Token economics

» 0.5% of IEO proceeds will be allocated to the DIGIPHARM charitable foundation (to be

established) with the goal to develop sustainable health related services in third world

countries. DIGIPHARM will further commit 2.5% of net profits per annum towards the

charitable foundation. If the foundation cannot be established due to regulatory or

legal reasons, DIGIPHARM intends to allocated the above mentioned funds to a third

party foundation with similar goals.

» Patients can also choose to redirect their rewards for data contribution directly to the

DIGIPHARM charitable foundation or affiliated third party foundations.

9.4 Commitment to charitable causes


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DIGIPHARMV2.4 (04/2019)

[email protected]

www.digipharm.io

DIGIPHARM - Healthcare Beyond Barriers. Bringing value-based healthcare to life using blockchain technology.