Practical aspects of early phase oncology trials the oncologists view

Transcription

1 Practical aspects of early phase oncology trials the oncologists view S. E. Al-Batran, MD Head, Institute of Clinical Cancer Research (IKF) University Cancer Center (UCT) Nordwest Hospital Frankfurt

2 Outline Doctor and patient motivation to make a clinical trial Challenges facing patients Challenges facing doctors Patient informed consent Instruction of Institute of Clinical Cancer Research (IKF) Recommendations

3 Doctor motivation Type 1, the cancer care type Quality assurance: German Cancer Society requires 10% patient treatment within Clinical trials phase-i/ii trials help attracting patients to the own hospital phase-i/ii trials offer more chance of authorship than phase III Focused on cancer care

4 Doctor Motivation Type 2, the professional clinical researcher Dedicated clinical research unit Focused on clinical research phase-i/ii trials are a substantial component of study portfolio financial aspects are very important Provides high quality research

5 Patient Motivation Drugs not available and patient failed standard Treatments First line setting and randomized trials PK or PD trials with drugs already on the market Low chance of therapeutic benefit in early phase and/or dose escalation trials Placebo controlled trials Phase 1 trials

6 What Leads Patients to Participate at a Clinical Trial? a hopeful treatment option more attention, quality of care, better infrastructure financial compensation physicians recommendation patients love to help improving treatment

7 Offering patient a Clinical Trial Patient is looking for a Clinical trial at presentation (highly motivated) Patient is seeking standard care (less motivated) Talk about treatment options then offer a trial Talk about the study and then inform about other options Patients want to know what their benefits will be!

8 Patient Informed Consent Procedure Very time consuming and emotional A dynamic process In oncology, it is optimal when the investigator is experienced in the field of disease

9 Informed consent - main aspects - The clinical trial What is the main purpose of the study? And Why is this study important to the patient? What are the chances that the study drug will work? And What kinds of risks/side effects are involved? Insurance! How much of patient time will the study take? Does the study involve randomization, placebo or a treatment already on the market? The patients care What kinds of tests will be done? Will cause discomfort or they hurt? If so, for how long? How will the tests in the study compare to tests the patient would have outside the study? Will the patient be able to continue to see his own doctor during the study? Will the patient be able to continue to take his regular medications during the study? (drug interactions have to be considered) If the patient has side effects, can they be treated during the study? Personal matters of the patient Who will review information collected during the trial? What happens if the patient decides to quit the study? Can the investigator take the patient out of the study even if the patient wants to continue? Compensation and costs Does the patient has to pay for any part of the study? If so, will insurance cover these costs? What about travel costs? To which extent? Will the patient receive compensation?

10 Informed Consent - problems - informed consent forms are developed to meet legal requirements the informed consent forms of the last oncology trial submitted to our ethic committee comprised 3 copies of 23 pages each, requiring 16 signatures!

11 Examples Patient with esophageal cancer, randomized trial in first line setting Patient with colorectal cancer, a PK trial with a drug already on the market Patient with pancreatic cancer, randomized trial in the adjuvant setting

12 Challenges Facing Patients unawareness of the possibility of enrolling in a trial difficulties in locating a trial geographic challenges significant travel and time costs patients often do not qualify for a clinical trial interruptions of the care of their regular doctor physical and emotional strains extensive paperwork associated with the informed consent mistrust of industry-sponsored trials

13 Challenges Facing Doctors the time and financial demands of clinical trials the divide and separation between clinical research and clinical practice the increasing complexity of regulations the increasing complexity of contracts less enjoyment from participation (e.g., increasing business aspects, contract research organization pressures data collection challenges (more complex CRFs, queries, quality control, pay for performance).

14 At least for early trials professional clinical trial unit, fully separated from clinical practice is required

15 Inadequate Compensation acc. To Offical Scale of Fees - (GOÄ) Who covers: Regular safety conferences Queries associated with data cleaning (hundreds to thousands) Preparing and stand by for on site monitoring visits Audits and quality control Unscheduled visits Very complex set-up and contracts increasing complexity of CRFs Increasing administrative issues.

16 CRO vs. Doctor More work = More money More CRO = More work = same money

17 Referral Physicians have disincentives to refer their patients to clinical trials German law does not allow significant compensation a mechanism to adequately compensate physicians for referring patients to clinical trials could improve recruitment rates Making it easier for community-based physicians to participate actively in clinical trials could also have a positive effect on patient recruitment

18 IKF established in 2010 as a part of the University Cancer Center Frankfurt to support clinical cancer research in the region of Frankfurt

19 Patients Network of 180 Collaborators in Germany Patients Krankenhaus Nordwest Biomarker Labor Phase I unit QMS Studies Pharmaceutical Biotech Akademie

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21 Recommendations for Designing/Conducting early Phase Trials Incentives for patients and doctors Realistic in/ex criteria, as inclusive as possible Select centers with professionally managed, dedicated, phase-1 units, do not accept mixed care/facilities Provide adequate compensation for all components, discuss with investigator in advance (do not argument with other investigators/ec)

22 Recommendations for Designing/Conducting early Phase Trials Do not leave drafting agreements and negotiations to the legal department Do not leave drafting PIC to the legal department Prefer CROs who have established long-term collaborations with centers Experienced representative of sponsor or CRO should be present on phase 1 unit when first patients are treated and documented