PLACING THE RIGHT BETS THE DIGITAL CLINICAL TRIAL:

RETHINK RESHAPE RESTRUCTURE… FOR BETTER PATIENT OUTCOMES

2

The next decade promises both tremendous potential and significant disruption for the biopharmaceutical industry as companies transition their focus from blockbuster products and volume based models to specialty products and value based models. Simultaneously, both the science and development operations are becoming increasingly more complex, with an average drug development cost of $2.6 Billion per product.1 As development costs and complexities soar, stakeholder (e.g., patients, investigators, payers) expectations continue to evolve at pace with technology advancements creating the need for a more convenient and personalized approach for product development. Staying abreast of these challenges will require a focus on innovation and patient outcomes.

2

3

Fortunately, new digital technologies exist to optimize the clinical development process, and more broadly the entire Research and Development (R&D) value chain. Academic research shows that digitalization will be fueling one-third of the growth and an estimated 40 percent of the profitability in the pharmaceutical market by 2020.2 Accenture’s industry research has shown that R&D executives recognize digital as a primary driver to deliver patient outcomes. Furthermore, companies embracing digital self-report stronger performance across several key R&D capabilities.3 Yet, many companies are slow to embrace digital at an enterprise level, due to perceived compliance risk, evolving regulator guidance, technology maturity, and an ambiguous return on digital investments. The overall picture: our industry’s embrace of digital lags that of other industries as well as stakeholders’ expectations.

Gartner rightly defines digitization and digitalization as two different activities. Digitization is simply changing from an analog to digital form, whereas digitalization is leveraging technology to revamp a business model to invoke new value-producing capabilities.4 We believe R&D organizations, and pharmaceutical companies more broadly, should boldly embrace digital technologies, rethinking both operating models and cultures. Our industry has, in the past, experimented tepidly with digital technologies in ways that fail to open the rich potential they have to solve pressing industry

challenges. In the early 2000s, enterprise Electronic Data Capture (EDC) solutions became available with the potential to significantly reduce the data entry burden to sites and increase speed to high-quality clinical trial data. However, the capability was not transformed holistically; paper-based systems were simply replaced by digital tools without the thorough consideration of how the technology could revolutionize clinical trial data capture. As a whole, the industry missed out on the expected value proposition. Today, nearly twenty years later, paper studies are still in use.

Unless our industry confidently embraces the holistic digitalization of R&D, the coming era will simply continue a slow trend of turning analog processes digital.

Accenture’s recent Point of View papers, “Industry at a Crossroads”3 and “Digital’s transformative power across R&D,”5 define key industry imperatives and describes how digital contributes to each.

In this paper Accenture will explore how digital capabilities can create value in clinical trials; specifically, in trial design, start-up, execution and closeout. Across these phases, digitalization will help drive superior outcomes in clinical trials, reduce costs and development cycles and enhance stakeholder interactions.

If we repeat history and fail to embrace the transformational potential of technology innovation, we will miss the opportunity to deliver significant value to patients, healthcare professionals and shareholders alike.

We believe R&D organizations, and pharmaceutical companies more broadly, should boldly embrace digital technologies, rethinking both operating models and cultures.

4

THE VISION: END-TO-END DIGITAL CLINICAL TRIALSMany R&D organizations are evaluating individual, niche use cases within the clinical trial process, like wearables or electronic informed consent. Surprisingly, few are exploring the digitalization of the end-to-end clinical trial processes and driving adoption globally across products and R&D functions. As previously defined in “Digital’s transformative power across R&D” Accenture recommends this broader application of digital aligned to three industry imperatives:

Improving patient connection and engagement Achieving a meaningful patient outcome requires gaining insight into patients’ needs, which consists of a more comprehensive understanding of the disease and new interaction models to improve participant experience. Historically, the patient’s involvement with a clinical trial is simply providing their data. Traditional trial endpoints often ignore a wealth of perspectives that can contribute to understanding patients holistically. Additionally, patients seldom have access to their data nor the results of the trial.

Growing a digitally-empowered workforce As the industry moves to a value-based model, the workforce must evolve from a static, one-size fits-all approach to a more flexible and dynamic operating model capable of balancing operations, diverse stakeholders, risk and value. We must increase the digital IQ of today’s labor force to harness the power of digital and the value it unlocks.

Digital technologies could allow organizations to operate in vastly more collaborative ways. When an organization is digitally enabled, data flows freely between disparate systems, functions and departments and better insights are possible.

Using data-driven insights and decision making Last, we must harness the operational and scientific data, detect and interpret signals from clinical trials, and uncover meaningful insights that drive action in real-time about trials, programs, and the overall portfolio. By combining various new and historical data types, R&D organizations can better predict a patient, a product, or operational outcome, as opposed to continually looking in the rear-view mirror.

Patient connection and engagement

Digitally empowered workforce

Data-driven insights and decision making5

1 2 3

5

As shown in Figure 1, there are opportunities across all the clinical trial phases to achieve a broad application of digital that is aligned to the three imperatives and creates demonstrable value.

In a fragmented and fast-moving market such as this, a good place for sponsors to start is by asking, “Where do we place our bets?” To answer this question, every R&D organization needs a strategy aligned with their science, portfolio, tolerance of risk, ability to invest, and willingness to navigate uncharted territory.

Real-word evidence in design of protocols and modeling expected outcomes

Adaptive trial design

Patient articulated outcomes in product and program design

STUDY DESIGN/PRE-STUDY

DIG

ITA

L M

ETH

OD

SVA

LUE

STUDY START-UP STUDY CONDUCT STUDY CLOSEOUT

Social platform for patient recruitment and ongoing trial awareness

Site and patient identification using analytics

Digital tools for screening, consent and cohort randomization

Optimized site start-up leveraging digital platforms

Electronic supply chain management eLabels for optimized drug authorization, shipment and reconciliation

Automated data analysis

Automated generation of TLF&Gs (Tables, Listings, Figures and Graphs)

Electronic submission and filing for regulatory review

Digital tools to thank patients and provide results/data

eSourced collection and cloud-based data aggregation

Wearable direct data capture

Near real-time access

Ongoing data interim analysis

Patient compliance & adherence digital tools

Real world/EMR data as a placebo arm

Predictive analysis and risk identification; improved protocol design

Faster site patient identification and enrollment

Faster site start-up; increased patient understanding & compliance

Transparent, effcient, and cost effective delivery

Faster and more transparent access to data

Improved speed to market

Increased patient understanding and compas-sionate care

Real time data access, monito- ring, control; improved patient experi- ence

Early detection of data trends; decreased early withdra- wals

Real time data access, monito- ring, control; improved patient experi- ence

Figure 1: Accenture’s Point of View on digital capabilities in clinical trials3

6

TRIAL DESIGN: USING DATA, ADAPTIVE TRIAL DESIGN, AND INCLUSION OF PATIENT PERSPECTIVES TO ENHANCE CLINICAL TRIAL DESIGN

Traditionally, sponsors have designed and executed trials to minimize variables and increase the likelihood of success. However, this approach often lacks flexibility and is without empirical assessments pointing to a successful outcome, which has resulted in an unacceptable level of failure rates that have plagued the industry for years. These same trial designs impose significant burden on investigators, patients, and caregivers. Poor trial design, such as the use of inappropriate inclusion and exclusion criteria, unrealistic recruiting targets, and excessive data collection, without clear adherence strategies or focus on relevant outcomes have negatively affected development success.

UNDERSTANDING THE CURRENT LANDSCAPE AS INPUT TO PLACING DIGITAL CLINICAL BETSWhile most sponsors are investigating the potential of new digital capabilities, the sheer volume and diversity of options has led to fragmented adoption of digital, resulting in “pilot paralysis” and lack of consistent, enterprise adoption. The following sections explore the traditional clinical trial phases, the digital opportunities to consider, and the value created by embedding these new capabilities.

R&D organizations can leverage real world evidence (RWE) and real world data (RWD) to transform the way trials are designed. For our purposes we define RWE as key conclusions derived from published studies in peer-reviewed journals, and RWD as data that describes current standard of care, gaps and deficiencies in the care model, and social or patient-reported data.6 RWE and RWD help sponsors leverage previous trial success and failure to predict future outcomes while considering patient needs and trial feasibility prior to enrolling a trial’s first patient.

6

7

Adaptive clinical trials and the use of analytics underpin dynamic operations during trial execution, as sponsor resources can see real-time performance and engage in more meaningful site interactions. Leveraging RWE, RWD and analytics could help sponsors target the right patient population at the right time, while effectively communicating with sites, thereby reducing delays and manual intervention.

Adaptive trial design and execution is not a new concept, still the Tufts Center for Study of Drug Development found only 20 percent of active studies are leveraging simple adaptive protocols. Adaptive approaches are generally not incorporated until the execution of Phase III trials7 yet earlier use of simple adaptive designs can decrease trial costs by 5 to 10 percent.8 Accenture believes even greater value could be created through increased success rates that result from more sophisticated adaptive design, such as adaptive dosing.

Outside the pharmaceutical industry, predictive analytics and adaptive design are in daily use. For example, Disney™ leverages data and predictive analytics to forecast park attendance to inform and set operations including park hours, performance times, and required staffing, vastly improving the overall customer experience.9 However, the use of data and analytics alone is not enough to transform a stakeholder’s experience and operations. Digitalization of trial design requires transformation beyond the use of data and adaptive trial design.

Traditional protocol development often consists of consultation from key opinion leaders, physicians, publications, and operations. However, our industry has yet to consistently leverage the input of the key trial stakeholder—the patient. By incorporating the experiential knowledge of patients or their caregivers living with a disease, sponsors can refocus on the patient population’s needs and affect trial success rates. When considering patient input on trial design, along with feedback from caregivers and advocacy groups, a positive impact on trial execution can occur. Specific observations include positive influences on participant recruitment and retention—two major drivers of clinical trial duration and cost.10 Digital channels, such as interactive patient websites and discussion forums, could be used as cost-effective ways to engage with a broad community of patients to understand outcomes that matter most.

To design meaningful trials that reduce burden and improve outcomes for patients and R&D stakeholders alike, sponsors should move beyond the simple use of RWD and RWE and look holistically to identify the unique data inputs and its applicable source (e.g., health records, wearables, patient interactions). To understand what matters most, sponsors should interact with patients differently to gain their insights, whether through simple protocol input or ongoing interactions through digital technologies.

To design meaningful trials that reduce burden and improve outcomes for patients and R&D stakeholders alike, sponsors should move beyond the simple use of RWD and RWE and look holistically to identify the unique data inputs and its applicable source.

8

TRIAL START-UP: USING DIGITAL TOOLS TO OPTIMIZE SITE IDENTIFICATION AND ENGAGEMENT

Site recruitment, retention and monitoring account for approximately 30 percent of trial costs11; yet, clinical trial sites differ markedly in performance and experience. Almost 50 percent of all trials fail to achieve planned patient enrollment targets; the Tufts Center for the Study of Drug Development estimated that 11 percent of clinical trial sites fail to enroll any patients at all and an additional 37 percent under-enroll during a given study.12 Recruitment rates vary significantly by site even though all sites receive the same evaluation for participation in the trial, protocol training, and support by the sponsor.

Predictive analytics using historical performance data could help sponsors identify and avoid low performing sites. Leveraging electronic health records (EHR) to model patient populations based upon inclusion and exclusion criteria can help assess the desired population viability and potentially optimize successful recruitment probability. Most CROs and sponsors, as well as many vendors, have access to site databases and RWE, yet many are inconsistently leveraging this data to optimize site selection.

The insights from analytics could help identify investigators, clinics or localities with a high occurrence of target patient populations and, consequently, improve clinical trial recruitment.13

Leveraging electronic health records (EHR) to model patient populations based upon inclusion and exclusion criteria can help assess the desired population viability and potentially optimize successful recruitment probability.

9

Opportunity exists to digitalize clinical development through automation of processes, while contributing to improving engagement with site stakeholders.

Clinical trial start-up and site interaction can be significant pain points for site personnel, who are key stakeholders to clinical trial success. Fortunately, opportunity exists to digitalize these activities through automation of processes, while contributing to improving engagement with site stakeholders. To address similar needs, companies outside pharma R&D are utilizing artificial intelligence (AI) capabilities such as robotic process automation, natural language processing and machine learning. For example, the insurance industry is leveraging AI for simple case processing and standardized underwriting, as substitution for manual effort and generalized trend detection. While our industry is exploring AI in patient safety, there is opportunity to bring similar technologies into the site selection process. By embedding these tools, sponsors could further help to improve quality site selection, reduce non-value added activity, and reduce costs.

To improve site interactions, digital technologies such as web-based remote learning and investigator platforms have already enabled the delivery of content and services to sites. More value can be created with a platform approach, defined as supporting multiple capabilities and personas across an end-to-end business process, creates a single point of access for sponsor interactions and can help enable better site management and training of trial staff—activities that typically account for 50 percent of trial costs.8 Digital-enabled site selection and interaction can reduce these site-related costs by 10 percent.8

A platform approach, defined as supporting multiple capabilities and personas across an end-to-end business process, creates a single point of access for sponsor interactions and can help enable better site management and training of trial staff—activities that typically account for 50 percent of trial costs.8

10

Patient identification and recruitment delays—which can extend trial duration by as much as 200 percent8—are leading factors in trial delays and cost overruns. Digital technologies could expand the channels for identifying patient populations beyond traditional approaches (e.g., site databases) and deepen the effectiveness of means that exist and are in use today.

Digital channels have improved identification and recruitment performance in recent trials and have increased the understanding of various patient populations. In 2015, automated eligibility prescreening —a process to compare inclusion/exclusion criteria with EHRs to proactively identify patients—was tested. Compared to traditional recruitment methods, leveraging this capability can help reduce overall workload by 92 percent.14

TRIAL CONDUCT AND CLOSEOUT: LEVERAGING DIGITAL TOOLS TO ENHANCE PATIENT RECRUITMENT AND TRIAL ADHERENCE WHILE SPEEDING TIME TO DATABASE CLOSE

Patient identification and recruitment are leading factors in trial delays.

Digital channels can help reduce overall workload by 92%

10

11

Digitally enabled patient engagement has also increased recruitment performance and improved patient experiences. Using familiar tools such as social media, mobile apps, and patient association platforms, sponsors can expand access to patient populations and accelerate enrollment.15 Leveraging these tools, patients can access personalized information about clinical trials and complete pre-screening questionnaires to expedite the selection process.

In addition to empowering patients to self-select, “-omics” profiling (referring to fields such as genomics, proteomics and metabolomics) could further refine and improve patient identification. Some industry participants are combining diagnostics with analytics to identify prospective participants in trials using RWD. With these techniques, sponsors could augment internal data with relevant external data from patient monitoring programs (e.g., NHS in UK, Medicare in US), third-party vendors, and networks of clinics providing anonymous patient data.

Effective patient recruitment is a prerequisite for successful and timely trial execution, but it does not guarantee a successful outcome. The overriding goal is to collect the right data to support submission, approval and, eventually, market access. However, participant attrition often slows trial execution and the path to approval. In fact, non-adherence, missed data capture and data inconsistencies can together lead to attrition rates as high as 30 percent.16

Smartphone apps and wearable devices enable investigators and sponsors to monitor and control adherence remotely—without manual intervention and in real-time.

Several digital and mobile technologies can be deployed to better manage adherence and thus impact attrition. Smartphone apps and wearable devices enable investigators and sponsors to monitor and control adherence remotely—without manual intervention and in real-time. Highly sophisticated tools (e.g., connected inhalers, digestible trackers, wearables) with electronic data capture capability will not only reduce the rate of missed data, but can help improve data quality and eliminate effort required to edit and clean.

When combined with analytic capabilities, these new sources of remote data capture and patient interactions have a positive impact on trial timelines. With improved patient monitoring and adherence, there is potential to decrease early terminations and improve predictability of trial timelines. With all these factors combined, there is potential to decrease trial cycle times (e.g., time from visit to data entry, time from last subject last visit to database close) and enable informed and timely decision-making.

12

To realize the benefits of leveraging digital in clinical trials, several actions could help to accelerate the transformation, make it sustainable and amplify the investment. These consist of:

CHOOSING YOUR DIGITAL BETS AND IMPROVING THE PAYOFF

Determine the unique needs of all clinical trial stakeholders (e.g., sponsors, sites, patients) to inform a digital clinical trial strategy. Consider prioritization of a key therapeutic area or selecting on pilot product.

Accenture believes having these factors in place would allow sponsors to broadly apply digital capabilities aligned to the three imperatives that are reshaping the R&D landscape—the need to pivot to the patient, advance next generation operations models, and drive scientific and operational excellence. An effective digital strategy will support each, while bringing the industry in line with other sectors.

Define and implement a digital clinical trial strategy and plan aligned to a broader R&D digital strategy which considers your organization’s unique appetite for risk and desire to be viewed leading or following.

Evaluate and incorporate the ongoing and planned digital pilots into the digital clinical trial strategy weighing prior successes and failures and considering the distinctive needs of each therapeutic area.

Confirm alignment across top-level management to communicate and set the digital clinical agenda, structure and culture within the development organization.

Embed and test the selected digital initiatives and document the success and failures to continue scaling the right tools at the right time to new products or therapeutic areas.

13

With digital, the future of clinical trials is bright and the mitigation of today’s industry challenges seems possible. Sponsors will be able to reimagine how they conduct the critical activities of product development, which would measurably improve patient experiences and outcomes. By looking at patients and diseases holistically and interacting with patients differently, the digitalization of clinical trials would help:

Feed insights back into research and early development to improve disease targeting and protect future patients a burdensome trial or therapy experience

Find the patients that benefit the most from a selected therapy and enroll in high performing sites

Reduce the risk for all stakeholders by identifying issues in real-time, or better yet, predicting them before they occur

Digital enablers are inherently in a constant state of evolution, thus sponsors need not—and should not—wait for ‘perfect’ digital tools or solutions. Rather, to bring new therapies to patients over the next decade and to prepare their organizations for the transformation that will come with the use of these technologies, sponsors must define the strategy that meets their unique goals and appetite for risk, while embracing digital capabilities available today and continuing to transform as new solutions and stakeholder expectations emerge.

This is not a spectator sport—traditional industry leaders will either disrupt, or be disrupted. Sponsors who “get in the game” and begin to place their digitalization bets will find themselves in the best position to be leaders in the future of clinical trials.

This Point of View paper is part of an ongoing Accenture thought leadership series addressing the role of digital in R&D. Visit www.accenture.com/digitalclinicaltrial and see related content.

CONCLUSION

13

Copyright © 2017 Accenture All rights reserved.

Accenture, its logo, and High Performance Delivered are trademarks of Accenture.

ABOUT ACCENTUREAccenture is a leading global professional services company, providing a broad range of services and solutions in strategy, consulting, digital, technology and operations. Combining unmatched experience and specialized skills across more than 40 industries and all business functions—underpinned by the world’s largest delivery network—Accenture works at the intersection of business and technology to help clients improve their performance and create sustainable value for their stakeholders. With more than 394,000 people serving clients in more than 120 countries, Accenture drives innovation to improve the way the world works and lives. Visit us at www.accenture.com.

ABOUT ACCENTURE LIFE SCIENCESAccenture’s Life Sciences group is dedicated to helping companies rethink, reshape or restructure their businesses to deliver better patient outcomes and drive shareholder returns. We provide end-to-end business services as well as individual strategy, digital, technology and operations projects around the globe in all strategic and functional areas—with a strong focus on R&D, Sales & Marketing and the Supply Chain. We have decades of experiences working hand-in-hand with the world’s most successful companies to improve their performance across the entire Life Sciences value chain. Accenture’s Life Sciences group connects more than 10,000 skilled professionals in over 50 countries who are personally committed to helping our clients achieve their business objectives and deliver better health outcomes for people around the world.

This document makes descriptive reference to trademarks that may be owned by others. The use of such trademarks herein is not an assertion of ownership of such trademarks by Accenture and is not intended to represent or imply the existence of an association between Accenture and the lawful owners of such trademarks.

REFERENCES1 Cost of Developing a New Drug. 2016. Tufts Center for the Study of Drug

Development. 2 All to win? Or all to lose? Driving digitization in Life Sciences. 2015. https://www.

accenture.com/us-en/insight-all-win-all-lose-driving-digitization-life-sciences3 Industry at a crossroads: The rise of digital in the outcome-driven R&D

organization. 2016. https://www.accenture.com/us-en/insight-injecting-digital-rd-journey-patient-outcomes

4 Gartner. IT Dictionary. 2016. http://www.gartner.com/it-glossary/digitalization/5 Digital’s transformative power across R&D: Keeping pace with stakeholder

expectations. 2016. https://www.accenture.com/in-en/insight-digital-transformative-power-across-rd

6 Elton, Jeff. The Reality behind Real-World Data and Real-World Evidence. 2015. http://social.eyeforpharma.com/column/reality-behind-real-world-data-and-real-world-evidence

7 The Adoption and Impact of Adaptive Trial Design. 2013. Tufts Center for the Study of Drug Development.

8 Improving Protocol Design Feasibility to Drive Drug Development Economics and Performance. 2014. Int J Environ Res Public Health

9 Corporate Profile: How analytics enhance the guest experience at Walt Disney World. 2012. Analytics Magazine. http://analytics-magazine.org/corporate-profile-how-analytics-enhance-the-guest-experience-at-walt-disney-world/

10 Patient-Centeredness in the Design of Clinical Trials. 2014, Value in Health.11 Examination of Clinical Trial Costs and Barriers for Drug Development. 2014. ERG.12 The Cost of Clinical Trial Delays. 2014. Tufts Center for the Study of Drug

Development.13 Bring Down the Cost of Clinical Trials with Improved Site Selection. 2013. Clinical

Leader. 14 Automated clinical trial eligibility prescreening. 2015. J Am Med Inform Association.15 How Social Media Improves Clinical Trial Recruitment. 2015. iSwarm.16 Attrition rates, reasons and predictive factors in supportive

and palliative oncology clinical trials. 2013. Cancer.

FOR MORE INFORMATION PLEASE CONTACT:AUTHORS:Nicole Faust Cohen Managing Director Accelerated R&D Services—Consulting nicole.f.cohen@accenturePetra Jantzer Managing Director Accelerated R&D Services—Europepetra.jantzer@accenture.comIan C. Shafer Managing Director Accelerated R&D Services— Clinical Development Practice ian.c.shafer@accenture.comKatie M. Strasser Sr. Manager Accelerated R&D Services—Consulting katie.strasser@accenture.com

CONTRIBUTOR: Michael Heinke Manager—Accenture Business Strategymichael.heinke@accenture.com

VISIT US AT ACCENTURE.COM/LIFE SCIENCES

Follow us at @AccentureLifSci

Connect with us on LinkedIn

accenture.com/lifesciencesblog