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For the past several years, game and media producer Beth Rogozinski has turned her attention to making games for mental and behavioral health – some of which have been submitted to the FDA to be regulated as a Class Two medical devices and are available only with a prescription. These games are based on clinical data and random control trials – making the process of developing fun and engaging games even more challenging. Add to that the FDA oversight and rigorous testing and QA specifications and game making becomes serious business indeed. But well worth it. Outcomes with these games and apps can far exceed treatment as usual and for mental and behavioral health patients these games can provide the privacy, dignity and access that they’re never before had.
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Serious Games in a Regulated Environment: Games and Apps as Digital Medicine Beth Rogozinski, Chief Content Officer Serious Play Conference 2017
Agenda and Objectives Play and Games for Serious Health Issues Pear Therapeutics and Digital Medicine Agile Dev Meets Regulatory: reSET Case Study Enhancing within the Boundaries Brining Game Best Practice and Design to Healthcare 2 Confidential - Do Not Distribute
PEAR Therapeutics – the leader in digital therapeutics Our mission is to commercially develop and distribute clinically validated, FDA regulated, digital therapeutics to treat diseases of the brain in order to improve clinical outcomes and lower overall treatment costs PEAR is afully integrated digital therapeutics company, developing regulated, reimbursed, prescription digital therapeutics We are a venture-backed company with a 40-person team in Boston and SF with expertise in software design & engineering, clinical development, regulatory affairs, and product commercialization and reimbursement We have developed a modular, cloud-based platform to deliver eFormulationsTM and our lead product, reSETTM, significantly improved abstinence in 6 randomized controlled trials in Substance Use Disorder, paving the way for it to be the first FDA- approved digital therapy in 1H 2017. We also have programs treating Opiate Dependence, Schizophrenia, and PTSD and other serious disorders. Confiden'al – Do Not Distribute 3
Agile Game and App Development for Mental and Behavioral Health with Medical Regulatory Oversight Clinical Product Design Process 4 Confidential- do not distribute
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CNS: Huge Unmet Need Global patient pop. for CNS disease Billion patients U.S. Economic Burden1 for CNS disease, 2012 $ Billion 2.0 2 Addiction 366 0.4 Alzheimer’s disease Obesity Chronic pain 148 123 95 Depressive disorders 83 0.7 Attention disorders 77 Sleep disorders 75 1 Stroke 57 Traumatic brain injury 56 Vision 52 Hearing loss 50 0.9 Anxiety 47 Schizophrenia 33 Epilepsy 16 0 Spinal cord injury 15 Total pts served under- served un- served Parkinson’s disease 10 9 Multiple sclerosis Estimated U.S. economic burden of common brain-related illnesses exceeds $1.3 trillion per year and worldwide burden exceeds $2 trillion per year Approximately 80% of the world market for brain related treatments is currently either unserved or underserved 1. 2012 values; Includes both direct and indirect cost of disease Source: NeuroInsights, Office of Nat’l Drug Policy, American Psych. Assoc., Cost of Brain Disorders Europe 6 Confidential- do not distribute
Digital health is becoming the most effective means of delivering behavioral treatment programs “Of the 26 trials, 23 demonstrated some evidence of effectiveness relative to controls… Conclusion: Internet interventions for depression and anxiety disorders offer promise.” “In adolescents with mild to moderate depression, the remission rate for those using SPARX greater than that of the usual face-to-face therapy.” “Video game- based training resulted in performance benefits with enhanced sustained attention and working memory...and preservation of multitasking improvement 6 months later.” 8 Confidential- do not distribute
Neuroplasticity: Chemistry + Cognitive Training + = Chemical agent (i.e. supplement or medication) Experience- dependent cognitive and rehab programs Current standard of care 9 Confidential- do not distribute
Digital therapies create medical value in areas of high patient need – Mental and Behavioral Health The US spends ~ $1.3 Trillion per year on CNS illnesses (psychiatry, neurology, and pain) with 80% of the world market currently unserved or underserved High Unmet Need Few new drug therapiesare set to come to market for CNS diseases, and the pipeline is particularly thin for mental health and addiction conditions Few New Therapies The Affordable Care Actand the Mental Health Parity and Addiction Equity Act are driving reimbursement of care for brain related diseases including new devices and drugs Favorable Reimbursement Software-based therapies have shown efficacy in treating brain related diseases and also in enhancing the efficacy of approved CNS medications Clinical Proof of Concept 10 Confidential - Do Not Distribute
Healthcare Psychographic Segments Proactive Reactive Strong Survivors (27%) • There are more important things in my life to focus on than improving my health • Live in the “here and now” Balance Seekers (18%) • Open to many ideas and options, as long as they make sense for me • Need context to understand ideas and recommendations Priority Jugglers (18%) • Worry about my family’s health more than my own • Constantly on the go, juggling many responsibilities so getting sick is not an option Active Listeners (13%) • Look to physician and other healthcare professionals for guidance and direction on what to do to address my disease Self Achievers (24%) • Take ownership of my health and actively take steps to be healthy • Focus on achieving my goals and objectives • Disease is another challenge to overcome C2B Solutions
Proactive Target Audience Women, middle aged, healthy lifestyles, well educated, higher income, ac6ve and fit Who are they? • 60% are female • Primarily “Achievers” and “Belongers” goal oriented – successful -‐ Driven • Between the age of 35-‐65 (Sweet Spot – mid 45-‐54) • Married/aKached professionals with families and very busy lives • Above average educaMon level – managers, execuMves, professionals • Higher than average disposable income levels and spending tendencies • They are connected via tech, socially connected and integrated What do they look for in health/wellness • Professional and friendly communicaMons and style • Value, reliability – relaMonship and trust come first • Simple, easy to use system that fits their busy schedule • One stop place to hold medical records and other data – can be shared with docs • Price is not primary – will pay more at first – but demands quality • Transparent, open easy communicaMons and informaMon • Technical and mulM-‐plaWorm access Business Indicators: • Heavy user of technology • Connected across social networks, LI, FB, Tw • Involved in group events and community – K Factor • Fastest growing segments of casual gamers • Price not a top issue, but efficiency is • Willing to pay for Premium Services/Supplements Motivators: INTRINSIC efficiencies CONTROL socialCOMMUNICATIONS http://www.aafp.org/media-center/releases-statements/all/kits/052908.html
Proactive Identity Customer • Professional working manager/executive, professional Married with kids – lives in Bay Area – travels around the bay for meetings and events. Partner has good job at tech firm Health focused – bikes, runs, hikes, does yoga – passionate about fitness, food and wellbeing Competent and DIY focused – but smart enough to ask for help when needed Passionate about SERVICE and QUALITY Connected and involved in her community – volunteers and gets out to contribute from self and company Is honest and expects honesty and open communications • • • • • • Self-motivated Can be directly monetized Seeks help and connections Intrinsic rewards are enough
Reactive Target Audience Women, middle aged, lifestyle issues and concerns, less educated/lower socio-‐economic status, o;en mul6ple health concerns/symptoms Who are they? • 55% are female • Needs Driven and Emulators – can cross all categories • Between the age of 40-‐59 • Divorced, unemployed/under employed • Average or below educaMon level • Uninsured, underinsured or government insured • They are less connected via tech, and not socially connected or integrated What do they look for in health/wellness • Access and availability – cost and access paramount • RelaMonship with doctor/caregiver – may be transferred • Simple, easy to use system – easily frustrated • One stop place to hold medical records and other data – can be shared with docs • Price is a primary – may exchange ads/acMviMes for free access • Transparent, open easy communicaMons and informaMon • May have single point of access – oden phone or computer only Business Indicators: • They trust the doctor, but not medicaMons • May not be digitally inclined • Compliance requires reminders and rewards • Easily bored and frustrated • Ads in exchange for payment/Price is an issue • MoneMzaMon would be via external sources Motivators: EXTRINSIC Needs Driven REWARDSSOCIAL RECOGNITION
Reactive Identity Customer • • Working single mom Lives in suburban areas and takes public transit to work Family and socially focused - not health focused - but may be focused on looks and beauty products Competent and capable - Seeks outside help as a last resort for fear of seaming incompetent Demands and requires equal access and treatment Connected and involved in her family, church and local circles Works hard and desires recognition for work and achievements • • • • • Situational motivations May be directly monetized – though exchange of ads/actions may be preferred Will seek help locally – church, family Extrinsic and recognition rewards may be more compelling
Games and Apps as Medicine Traditional Emotional Motivation Game/App Approach Apprehension, uncertainty, wai6ng, expecta6on, fear of surprise do a pa6ent more harm than any exer6on. Florence Nightengale Notes on Nursing 1859 16 Confidential - Do Not Distribute
Games and Apps as Medicine 17 Confidential - Do Not Distribute
Serious Issues Limit the Impact of Digital Therapeutics Traditional business model PEAR’s approach • Focus on health and wellness use cases • Focus on diseases with high unmet need • Limited clinical evidence for efficacy; small longitudinal studies relying on patient reported data • Efficacy evaluated via RCTs versus current standard of care utilizing existing approvable endpoints • Due to regulatory limitations, unable to promote disease treatment claims or modify drug dosing • Filing for FDA approval with claims to assess/treat disease and integrate with medication • Unclear distribution channels with physician confusion regarding path to patients • Marketed directly to physicians as a prescription product with access codes conferring patient access • Lack of third-party payer reimbursement without clear means for coding and payment • Medical device with product codes and reimbursement supported by health economic analyses 18 Confidential - Do Not Distribute
The FDA and Regulated Healthcare • Formed in 1906 by Pres. Roosevelt to protect citizens against worthless “cures” and adulterated foods and pharmaceuticals • Continuously updated to reflect modern times • Focus – safety and efficacy FTC fines for: Lumosity, Carrot Neurotech, AcneApp 19 Confidential- do not distribute
Data Driven 20 Confidential- do not distribute
Subclinical Apps and Platform Live in 2015 Confidential- do not distribute 21
We have developed a pipeline of eFormulationsTM treating areas of high unmet medical need In-licensed Internal Content Partner Indication Stage Product Pilot study FDA PreSub Pivotal studies FDA FDA approval Prototype submission reSETTM Substance Use Disorder reSET-OTM Opiate Dependence Schizophrenia ThriveTM Combat-PTSD reCALLTM General Anxiety Disorder reVIVETM Insomnia PEAR-006 Traumatic Brain Injury PEAR-007 ADHD PEAR-008 Major Depressive Disorder PEAR-009 Acute & Chronic Pain PEAR-010 22 Confidential - Do Not Distribute
A Common Struggle – SUD and OUD a Nationwide Epidemic • In 2015 only 11% of the estimated 22.7 million Americans in need of treatment for SUD received any formal treatment • Over $740B in annual costs from healthcare, productivity and crime • Addiction and overdose have surpassed car accidents as a leading cause of death in young men • 91 people a day are overdosing and deaths > 2 jets a week crash landing • Health impacts are profound and include abscesses, cellulitis, pneumonia, heart failure, HIV and Hep C • High rates of comorbidities – causative or reflective directionality 23 Confidential- do not distribute
Why Digital Therapies are Needed Pear Tx Digital Treatment Current State of Care • Diagnosis occur too late – Jail, hospital, death • Stigma and shame • Expensive, not available and not scalable – Desserts of care for all mental health • High friction for patients – Removed from home, work, stressors and triggers • Inconsistent treatment • Digital can allow exploration and early intervention Private – apps are all HIPAA secure and CFR-42 compliant Effective, available and scalable – BYOD – patients already online Always on and always available – 168 hours in the week Consistent approach that is gamified and engaging and can be personalized • • • • 24 Confidential- do not distribute
Addiction: Enslaved • Learning disorder – double edge sword of neuroplasticity • Often have no positive feedback or affirmations in their lives – or the drug/substance confused with rewards • Success requires overcoming shame and focusing on the moment (MBSR) and learning new life skills • Risk taking patients particularly tied to rewards 25 Confidential- do not distribute
PROJECT 28 DAYS – PEAR-001 Persona 1 Anthony Addict DETAILS Over 30-‐40, Anglo Lives in a urban center Unemployed, on welfare Owns older smartphone Psychologically and Physiologically addicted Uses opioids 1/day Uses opioids habitually to stave off withdrawal Difficulty controlling drug-‐taking behavior Post rehab and going through city clinics Post-‐detox GOALS Hit rock boYom with an arrest and going through the long process of recovering from dependence Wants to stay out of jail via mee'ng terms of proba'on including treatment, counseling, and tes'ng • • • • • • • • • • • •
PROJECT 28 DAYS / PEAR-‐001 -‐ PEARTX ADDICTION TREATMENT APP V1 -‐ AGILE VISION BOARD A SMARTPHONE APP THAT, PAIRED WITH MEDICAL TREATMENT, IMPROVES OUTCOMES FOR RECOVERING SUD/OUD PATIENTS Needs • Rewards you for par'cipa'ng in your own treatment • Teaches you the proven skills and behaviors to overcome addic'on • Gives you the tools for a beYer life • Enhances the effec'veness of your treatments • By tracking progress, gives you and your doctor beYer info to help you Target Group Primary • 80% Male • Anglo • 28-‐46, median 37 • English speaking • Own a smartphone Product Business Goals Creates reoccurring revenue stream from city, county & state clinics Provides strategic value as our first FDA approved product Bellweather for poten'al pharma partners Validates IP and thus provides business proof to addi'onal investment and /or poten'al acquirers A smartphone app App that presents and test cogni've behavioral therapy App presents and tests fluency training App gives mo'va'onal incen'ves Server can push and app can display self tracking data to user • • • • • • Secondary • Physicians, Clinicians & Assistants • Medical Researchers • • •
reSET®, is on track to be the first FDA-approved digital therapy with efficacy claims for the treatment of substance use disorder (SUD) Introducing reSET® for treatment of SUD • reSET® is a prescription digital therapy for treating SUD by delivering addiction-specific Cognitive Behavioral Therapy (CBT), Fluency Training, and Contingency Management • The concept product was developed at Dartmouth’s Geisel School of Medicine by Lisa Marsch, PhD • reSET® and reSET-OTM have been evaluated in 5 published randomized clinical studies involving over 1500 patients, and has attracted more than $45M in National Institute of Health (NIH) funding1-4 • In a multi-center randomized trial consisting of 507 patients seeking treatment for SUD, reSET® enhanced abstinence versus in-office treatment (p = 0.003)5 • reSET®is projected for approval in 1H 2017 as a class II medical device with claims for treatment of SUD to and enhance abstinence and retention in treatment 1 Experimental &Clinical Psychopharmacology. 2008. 16(2):132-143. 2 Substance Use and Misuse. 2011. 46(1):46-56. 3 American Journal of Psychiatry. 2014. 171(6):683-690. 4 Journal of Substance Abuse Treatment. 2014. 46: 43-51. 5 Campbell et al. Am J Psychiatry. 2014. Confiden'al – Do Not Distribute 28
In the pivotal clinical trial, reSET doubled rates of abstinence versus treatment as usual (TAU) 507 patients with Substance Use Disorder at 10 nationwide treatment centers were randomized to 12 weeks of typical outpatient treatment (TAU) vs Product X with limited clinician exposure and abstinence was measured through urine analysis and self reports 50 40 % Abstinent 30 20 TAU Product X 10 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Week Population Time Point Product X TAU Odds Ratio (95% CI) P-value* All comers Week 9-12 29.7% (n=255) 16.0% (n=252) 2.22 (1.24, 3.99) 0.0076 Non-abstinent at start Week 9-12 10.1% (n=113 ) 3.0% (n=119) 3.59 (1.36, 9.48) 0.0099
reSET enhanced retention in treatment relative to treatment as usual (TAU) Treatment Retention 100 Percentage Remaining in Treatment 90 80 70 60 0 0 2 4 6 8 10 12 Time (weeks) TAU Product X P-value Patients remaining in treatment 63.5% (n=252) 72.2% (n=255) 0.0316 Patients receiving reSET were significantly more likely to be retained in treatment vs those receiving treatment as usual
reSET® enhanced retention in treatment relative to TAU, and patients showed strong rates of engagement Module Completion Treatment Retention 100 5 completed per week Percentage Remaining in Treatment Average # modules 4 90 3 2 80 Abstinent 1 Non-Abstinent 70 0 1 2 3 4 5 6 7 8 9 10 11 12 Time (weeks) 60 Module Retention reSET™ Treatment as usual (TAU) Average time spent on modules (in minutes) 60 0 2 4 6 8 10 12 Time (weeks) 40 reSET® TAU P = 20 Abstinent All- Comers Abstinent Non-Abstinent 36.5% (n=252) 27.8% (n=255) 0.0316 Non-Abstinent 0 1 2 3 4 5 6 7 8 9 10 11 12 Time (weeks) Patients receiving reSET® were significantly more likely to be retained in treatment Patients remained engaged with reSET® throughout the duration of the clinical trial Confiden'al – Do Not Distribute 31
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reSET includes includes both a patient-facing intervention and clinician-facing dashboards Patient Health Care Professional CBT Modules Fluency Training Contingency Management Module Use Cravings and Triggers Craving & Trigger Assessment Mobile Dashboard Concept Proficiency Abstinence and Appointments
Cognitive Behavioral Therapy (CBT) Modules for reSETTM Core Modules Optional Modules 1. Training Module 2. What is Functional Analysis? 3. Conducting a Functional Analysis 4. Self-Management Planning 5. Introduction to Problem Solving 6. Effective Problem Solving 7. Drug Refusal Skills Training 8. Seemingly Irrelevant Decisions 9. Coping with Thoughts about Using 10. Awareness of Negative Thinking 11. Managing Negative Thinking 12. Managing Thoughts about Using 13. Managing Negative Moods and Depression 14. Decision-Making Skills 15. Increasing Self-Confidence in Decision-Making 16. Introduction to Assertiveness 17. How to Express Oneself in an Assertive Manner 18. Introduction to Giving Criticism 19. Steps for Giving Constructive Criticism 20. Receiving Criticism 21. Giving and Receiving Compliments 22. Communication Skills 23. Nonverbal Communication 24. Social Recreational Counseling 25. Attentive Listening 26. Sharing Feelings 27. HIV and AIDS 28. Sexually Transmitted Infections (STIs) 29. Sexual Transmission of HIV and STIs 30. Drug Use, HIV and Hepatitis 31. Identifying/Managing Triggers for Risky Sex 32. Identifying/Managing Triggers for Risky Drug Use 1. Vocational Counseling 2. Financial Management 3. Insomnia 4. Time Management 5. Introduction to Relaxation Training 6. Progressive Muscle Relaxation Training 7. Progressive Muscle Relaxation Generalization 8. Introduction to Anger Management 9. How to Become More Aware of the Feeling of Anger 10. Coping with Anger 11. Relationship Counseling – Part 1 12. Relationship Counseling – Part 2 13. Relationship Counseling – Part 3 14. Hepatitis 15. Alcohol Use and risk for HIV, STIs and Hepatitis 16. Getting Tested for HIV, STI and Hepatitis 17. Finding More HIV, STI and Hepatitis Information 18. The Female Condom 19. Negotiating Safer Sex 20. Taking Responsibility for Choices 21. Birth Control Use and HIV and STIs 22. Living with HIV: Communication Skills for Disclosing HIV Status 23. Living with HIV: Drug Use and Immune System 24. Living with HIV: Managing Treatment and Medications 25. Living with HIV: Daily Routines to Promote Health 26. Living with Hepatitis C: Coping Skills 27. Living with Hepatitis C: Managing Treatment, Promoting Health 28. Naltrexone 29. Limited Alcohol Use 30. Alcohol and Disulfiram • 32 core modules and 30 optional modules • Each module intended to last ~20-30 minutes with real-world use suggesting average completion time of ~10 minutes • Content presented as a mix of video, audio, and still images reSETTM and reSET-OTM are not available for sale in the USA 34 Confidential- do not distribute
Tracking feature for self-report usage, cravings and triggers
Rewards for completing lessons and answering questions (Contingency Management) Behaviors are rewarded with opportunity to win monetary prizes in two ways: 1) by completing a set of proficiency questions, and 2) a clinician-entered clean urine drug screen result Monetary rewards are automatically added to a rewards card the patient receives during enrollment The patient receives the ability to spin the prize wheel to determine whether digital badges or monetary rewards will be awarded All rewards are of nominal value with average monthly reward of ~$30
Clinician-facing dashboards features: Abstinence and appointment compliance
reSETTM: Patient-facing features Cravings & Trigger Assessments Mobile Dashboard Patient Fluency Training Contingency Management CBT Modules reSETTM and reSET-OTM are not available for sale in the USA 40 Confidential- do not distribute
Overview of FDA Submission Process Pre-submission filing and meetings Acknowledgment of receipt QMS Established SOPs Written and Authorized SOP/QMS Training Administrative information document Introduction & Summary of Regulatory History Regulatory History: responses to FDA feedback Proposed Indications for Use Device Information and Summary - SRS – Software Requirements Specification (82) - SDD – Software Design Description Change Summary Between PreSub and De Novo device description Classification Summary Classification Recommendation Proposed Special Controls (for Class II devices ONLY) Supporting Protocols and Data (9 additional documents with 31 Appendices) Summary of Benefits Summary of known and potential risks to health Risk and mitigation information (5 with FMEA and DFUs for clinicians and patients) Benefit/Risk Considerations Device Labeling – 3 levels of labeling negotiations V&V – Validation and Verification (all content and aspects meticulously tested and retested with every new build) 41
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Dose Response Curve 43 Confidential- do not distribute
Multiple choice and fill in the blank questions are asked at the end of each lesson to ensure understanding Multiple Choice Example Fill in the Blank Example Which of the following is not a goal of attentive listening? a. letting a person know you are listening to them b. letting a person feel like you are listening c. making a person hurry to finish what they are saying d. building trust with the person who is talking “I must do this task perfectly without making ANY mistakes”, is an example of which type of negative thinking? a. black-and-white thinking b. positive thinking c. self-putdown d. perfectionism All of the following are goals of attentive listening except _________________. a. showing a person you are listening to them b. gathering information c. talking only about things that interest you d. building trust with the person speaking Avoiding eye contact when a person is talking to you is an example of poor_____________. a. verbal skills b. active listening skills c. inactive listening d. distraction • Approximately 5-10 questions follow each CBT module • Repetitive nature of questions developed from Fluency Training techniques • Patient must answer all questions correctly in order to advance to the next module • Missed questions are recycled back into the queue and asked again
Reframing One’s Story with CRAFT 45 Confidential- do not distribute
Storyand Your Brain Research shows that STORY: • Provides superior retention (memory and recall) • Provides improved understanding • Creates context and relevance • Creates empathy • Makes readers/listeners pay attention • Enhances the creation of meaning Neurologists have Proven that Humans are Wired for Story
Context IS Storytelling Nemesis, Love Interest, Obstacles, and Layered Emotions. DONKEY KONG (1981)
TheEight Essential Elements Hero’s Journey 1. CHARACTER 2. CHARACTER TRAITS 3. GOAL 4. MOTIVE 5. CONFLICTS/PROBLEMS 6. RISK & DANGER 7. STRUGGLES 8. DETAILS Order Disruption Chaos Conflict/Struggle ResoluMon
PROJECT 28 DAYS UIUX / Story world Aesthetic 90s action movies / GTA III illustrations
Grand Theft Auto meets the SIMS 50 Confidential- do not distribute