Session V: Perspectives from Patient Organizations - PowerPoint Presentation

1. Session V: Perspectives from Patient Organizations Jane PerlmutterThe Gemini GroupCTTIJohn AdamsPKU and Allied DisordersBest Medicines CoalitionAntoine DaherCasa HunterBrazilian Federation of Rare Disease Associations

2. ICH E6 June 4, 2020Patient Perspectives on Guidance for Conduct of Clinical Trials:“more lifeboats please”John Adams PKU and Allied DisordersBest Medicines Coalition

3. Patients: We need more lifeboats!

4. Black holes, Make Ethics Stick, Borders & CuresTOPICS:Gaps in communication with volunteer participants Ethics of human participant access to therapy post-trialGlobalization of clinical trials: patients & drugs need to cross borders Big deal when we can move a disease from untreatableBigger deal when we can move it to curable4

5. Who I am and how I got hereAs a child: mother open heart surgery1st in CanadaAs a father: child with rare disorderAs a spouse: wife died without diagnosisAutopsy: ALS & FTD Amyotrophic Lateral SclerosisFrontoTemporal DegenerationAdvocate:Co-founder & President, Canadian PKU and Allied DisordersCo-founder & President, Global Association for PKUBoard Chair, Best Medicines CoalitionCo-chair, Disability Tax Fairness AllianceMember, Citizen Advisory Group, HCP regulatory collegesPast Chair, Canadian Organization for Rare Disorders5Caregiver:

6. Patient: Polypharmacy6Multiple chronic conditionsCancer survivorClinical trial participantbrain ultrasoundrole of exercise in preventing or recovering from covert strokes

7. Ensuring all Canadians have safe and timely access to medications that have been shown, based on best available evidence, to improve outcomes for patients.Best Medicines Coalition: Mission7

8. Patient Journey: 10 days changed a lifeSon with PKU (phenylketonuria): genetic, newborn screeningnot life-threatening, only brain threateningStandard of care: protein restriction & synthetic substitution Tall, skinny weakling - no stamina, frequent illnesses, learning disabilityClinical trial, in Chicago, cross-border participantNeurotoxicity: 2 days ↓75%, ↓90% in 4 weeksStarted 8 days from first contact with Clinical Investigator (known to father)2 days to efficacy – led to normal, high-protein dietOutcomes: struggling Cs →As, university graduatenew speed record in 2-mile run at firefighters school (Texas A&M)8

9. Topics for renovating guidelines1. Black Holes of Communications: Reminders for/of informed consent –throughout participation, not just at front endBack end: communications gap after participation before publication and at publicationMake part of informed consent throughout2. Make Ethics StickHelsinki Declaration(s) of World Medical Association: Patient’s right to continue on therapy post-trial“Post-Trial Provisions: 34. In advance of a clinical trial, sponsors, researchers and host country governments should make provisions for post-trial access for all participants who still need an intervention identified as beneficial in the trial. This information must also be disclosed to participants during the informed consent process.”3. Patients, Drugs & BordersPandemic and non-pandemic: COVID-19 “essential travel” 4. Get Ready for Once & Done cell and gene therapies9

10. How do we move to health care with plenty of lifeboats?10Challenge ICH: Design and build better & more lifeboatsPatients: nothing about us without usPatients have the right to be impatient

11. ICH E6 June 4, 2020Thank YouJohn Adams PKU and Allied DisordersBest Medicines Coalition

12. Session V: Perspectives from Patient OrganizationsJane PerlmutterGemini Group734-604-5263janep@gemini-grp.com

13. Long-term cancer survivorActive, informed, and opinionated advocateProfessional experience in academia and industrial R&DCurrently, independent consultant Who am I?Jane PerlmutterGemini Group734-604-5263janep@gemini-grp.com

14. Clinical Research ExperienceParticipant in many clinical studies, but no interventional randomized controlled trialsProvided peer counseling to many patients considering enrolling in clinical trialsAdvocate member of:Clinical trial consortia Steering committee for innovative master protocol trials (I-SPY and TAPUR)IRBDSMBsGuideline committees, CTTI projects, working Groups Developing and delivered training on clinical research methods to advocates and young investigators…

15. JP Patient AphorismsPatients don’t have the luxury of patience All patients are the same—they want to live long, high quality lives; each patient is unique in what they mean by thisAbout me; with me (AIDs Advocates)

16. Obtain input from diverse patientsEngage patients/advocates in all work groupsAdopt both approaches as these ICH E6 is being developed and recommend them as part of final documentInclude Discussion of Patient Centered-Drug DevelopmentWhat it AddsUnderstanding patient needs, values and prioritiesMaking clinical trials attractive to potential participants and easy to participate inEnsuring diverse representation from the target populationEncouraging public support of clinical researchHow

17. Research Advocate Involvement Across the Clinical Trial ContinuumProvide information about unmet needsAssess interest of patient communityProvide feedback from patient community on sites, investigators, & study experienceServe on Trial Steering & Data Monitoring CommitteesProvide peer support during consentingSupport discussions with funders, sites & IRBSSupport trial awareness & recruitmentProvide input on study designAssist in creating informed consent document & patient education materialServe on FDA advisory & post-market surveillance committeesProvide FDA TestimonyPrepare lay summariesCo-author papers & postersCommunicate with patient community17

18. Some Specific Patient Issues to ConsiderDo not call us ‘subjects’; call us participants, patients or volunteersRemind investigators that informed consent is a continuing processEncourage sponsors and investigators to:Collect and report patient reported outcomesReturn both individual and aggregate results to trial participantsProvide guidance on appropriate use of Data Monitoring Committees that include advocate membersEmphasize the responsibility to publish results of both positive and negative trials

19. Make Trials More Patient- FriendlyFewer visits scheduled that are patients’ convenience Use of remote sites (e.g., blood tests), home visits, telemedicineElectronic consent and patient reported outcomesAllow cross-overInnovative randomization2:1 experimental to controlResponse adaptive randomizationUse of synthetic controlsLimit eligibility requirements; match intended real world use

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21. Stakeholder Engagement on ICH E6 Guideline for Good Clinical Practice Web Conference - Recommendations for versionAntoine Daher President

22. Casa HunterFounded on November 26, 2013;A non-profit advocacy group with no political or religious affiliation;It aims to ensure public solutions and create awareness in the private sector and society in general for patients with rare diseases.

23. RECOMMENDATIONS

24. Item 3. Research Ethics Committee/Independent Ethics Committee (REC/IEC)Item 3.1.4 – About Yearly Reviews of ongoing trials.Recommendation: For Rare Diseases, the period of 1 year is too long. We recommend a maximum period of 6 months for the review. Same for item 4.10.1.

25. Items 3. (REC/IEC) and 4. InvestigatorItems 4.8.15 and 3.1.7 - When Prior Consent is not Possible. (i.e., in emergency situations).Recommendation: In an emergency a prior consent should not be waived, since it could put our patients with Rare Diseases at an increased level of risk. It would be advisable to request a written consent form to the patient or his legal representative.Note: Taking the COVID-19 pandemic as an example, study protocols with hydroxychloroquine/chloroquine could generate cardiac complications for patients affected by a rare disease with cardiac involvement.

26. Item 4. InvestigatorItem 4.2.1 The investigator should be able to demonstrate (e.g., based on retrospective data) a potential for recruiting the required number of suitable subjects within the agreed recruitment period.Recommendation: For Rare Diseases, the number of patients affected by a rare disease is challenging to estimate. We usually have inaccurate estimates of the number of people affected by a rare disease, which may also impact the conclusion of the study during a previously established period.

27. Item 4. InvestigatorItem 4.3.3 Informing the subject’s primary physician about the participation in the trial.Recommendation: In studies involving patients with Rare Diseases, the participation of a physician specialized in rare diseases and with knowledge of the disease, usually the geneticist, must be informed throughout the study.

28. Item 4. InvestigatorItem 4.6.6 The investigator, or a person designated by the investigator/institution, should explain the correct use of the investigational product(s) to each stakeholder.Recommendation: At no time it is specified in the manual that for infusions with biological medications, the need for training for: PreparationInfusion TimeAdministration TechniqueAmong others

29. Item 4. InvestigatorItem 4.12 Premature Termination or Suspension of a StudyRecommendation: It may generate risks and compromise the participants' health, and even cause their death when there is no other treatment available.In the event of an interruption, the Independent Data Monitoring Committee (IDMC) should be a party to the process, and recommend whether the sponsor should suspend, continue, or modify the trial.

30. Item 5. SponsorItem 5.6 Investigator SelectionRecommendation: Requiring Training and Experience. For rare diseases, the preparation, application, administration of the drug under investigation, must undergo extensive training. Inadequate performance of the procedures can jeopardize the effectiveness and safety of the study and its research participants. Item 5.18 MonitoringRecommendation: It is necessary to include an item addressing ongoing training of the medical team and any other professionals responsible for preparing the medication, for minimizing the risks related to the preparation. Consequently, guaranteeing the safety of the study and its participants."

31. Item 6. Clinical Trial Protocol and Protocol Amendment(s)Item 6.2 Basic InformationRecommendation: Include items for "description, justification, and technique for preparing the medication". The same recommendation is valid for item “7.3 - Contents of the Investigator's Brochure,” where the preparation technique of the drug must be present.Item 6.4 Design of the StudyRecommendation: This item may be incompatible for clinical trials with patients affected by Rare Diseases, as we are limited to several rules due to the number of research subjects. The same is true for the item (6.9.2) on carrying out statistical analysis, since some studies involve a minimal number of patients.

32. Final RecommendationAlthough the guide is applicable to rare diseases in most items, it is necessary to develop a specific guide for conducting clinical studies in rare diseases, as it is already the case for pediatric and geriatric populations

33. Thank you for the opportunity to participate in the review of this important ICH guideCasa Hunter Review TeamDr. Raphael Fernando Boiati (Casa Hunter)Dr. Roberto Giugliani (Casa Hunter)Dr. Marcelo Yamamoto (Casa Hunter)Plinio Gherardi (Casa Hunter)Antoine Daher (Casa Hunter)

34. Our fight is for life. This photo by Unknown Author is licensed under CC BY-NC

35. M. Khair ElZarrad, E6 RapporteurFood & Drug AdministrationClosing Remarks & Plans for Day 2

36. M. Khair ElZarrad, E6 RapporteurFood & Drug AdministrationThank YouPamela Tenaerts, ModeratorClinical Trials Transformation Initiative