FEASIBILITY ASSESSMENT: CORNERSTONE OF SUCCESSFUL CLINICAL TRIAL PLANNING VERONIKA FEKETE, MD MANAGER FEASIBILITY RESEARCH AND PATIENT RECRUITMENT SERVICES, PSI CRO 1
WHAT CAN GO WRONG WITH A CLINICAL TRIAL >90% of all clinical trials are delayed due to over-ambitious timelines and difficulty with patient enrollment. Roughly 70% of all trials are delayed from one to six months due to patient enrollment problems. 30% of PIs under-enroll in a given trial. Estimated 20% of PIs fail to enroll a single patient. Delays in the drug development process cost pharmaceutical companies billions of dollars per year. IF A CLINICAL TRIAL IS NOT WELL PLANNED IT WILL FAIL! 2
WHAT IS A FEASIBILITY STUDY? An analysis of the ability to complete a project successfully, taking into account technological, economic, legal, operational and scheduling factors. A feasibility study allow project managers to investigate the possible negative and positive outcomes of a project before investing too much time and money. Investopedia 3
WHAT FEASIBILITY ASSESSMENT SHOULD DEPICT 4
FEASIBILITY ASSESSMENT 10-20 YEARS AGO Doctor House, could you please tell me how many AML patients are seen on your Moon annually? 50 up to 60 But we need AML patients with red hair only. Can you please tell us how many of your AML patients have red hair? 30 up to 40 5
ENROLLMENT PROJECTIONS 15 YEARS AGO AND NOW Investigator projections (p/site/month) Proposed screening rate (p/site/month) Proposed enrollment rate (p/site/month) 2002 1.5 1.2 1.2 2008 1.3 0.9 0.7 2013 1.1 0.6 0.4 1.5 1 0.5 0 2002 2008 2013 PI SR ER NSCLC study with stage IIIb, IV patients who progressed on previous platinum-based regimen 6
WHAT HAS CHANGED IN ONCOLOGY TRIALS? Number of clinical trials Number of targeted therapies Number of unique procedures Number of eligible patients Longer trial duration Newly approved drugs Challenging environment for oncology trials 7
CASE STUDY #1: 2 ND -LINE NSCLC Comparison of pemetrexed + study drug vs. pemetrexed + placebo Eligible patients must be naive to pemetrexed Projected enrollment rate (patients/site/month) Germany 0.3 Italy 0.3 Czech Republic 0.3 Hungary 0.3 Russia 0.4 Achieved enrollment rate (patients/site/month) 0.23 0.18 0.13 0.43 0.68 Reason: changes in 1 st -line treatment to pemetrexed + cisplatin combination 8
% of NSCLC patients treated with pemetrexed in 1 st line 1 ST -LINE PEMETREXED USE IN NSCLC IN 2012 80% 60% 40% 20% 0% 9
AND IN 2014 Pemetrexed is routinely used in 1 st -line US Germany, France, Italy Spain, Belgium, UK Czech Republic, Hungary, Poland, Lithuania Pemetrexed is not routinely used in 1 st -line Estonia, Latvia, Romania Belarus, Russia, Georgia, Serbia, Ukraine Brazil, Mexico Chile, Peru, Argentina Israel 10
WHAT TO FOCUS ON DURING THE FEASIBILITY ASSESSMENT? Medical and clinical feasibility Standards of care Diagnostics methods routinely used? Investigators/patient motivation/benefit Study design Eligibility criteria Logistical feasibility Sample delivery timelines Imaging requirements Access to specific equipment (e.g. freezer, centrifuge, IMRT, etc.) Regulatory feasibility 11
FEASIBILITY HURDLES You have 3 days to deliver the RFP What do investigators think about the study? Commit to your projections but eligibility will change But do not contact any sites! 12
FEASIBILITY ASSESSMENT REQUIRES MULTIDISCIPLINARY INPUT Feasibility team Supported by highly professional experts with different background Feasibility specialist Medical expert Laboratory expert Regulatory expert Imaging expert 13
FEASIBILITY ASSESSMENT PROCESS 2 d a y s Protocol review by multidisciplinary experts Identification of key study challenges Comparison with in-house experience Comparison with industry experience Identification of site requirements and site profile 2 w e e k s Feasibility planning Communication with investigators Data analysis Scenario and feasibility report Challenges identified by investigators 14
WHAT FEASIBILITY CAN OFTEN PROVIDE? Clear and bright Lots of details Jumbled mess More questions than answers Studio with plaster head - Picasso 15
FEASIBILITY REPORT OFTEN LOOKS LIKE Attractive projection Blurred detail Understandable parameters The Path Monet 16
WHAT FACTORS AFFECT REAL ENROLLMENT? Finance Competition Regulatory Logistics Investigators projections Staff workload Benefit for patients 17
METHODOLOGY OF CALCULATING ENROLLMENT RATES Monthly availability of potential study candidates Investigator screening projections Complexity of early-phase studies (multiple assessments, heavy schedule) Indirectly competing trials consuming site staff time and resources Directly competing trials enrolling patients with the required indications Screening projections Screen failure rate Start up timelines Site Performance Factor Site Initiation Factor Effective enrollment rates 18
FEASIBILITY ASSESSMENT IS SCIENCE - ALWAYS MEASURE WHAT YOU DISCOVER Feasibility data must be verified: Over time With reality With all parties involved 19
CASE STUDY #2: NEWLY DIAGNOSED MULTIPLE MYELOMA TRIAL Study design: Newly diagnosed multiple myeloma not eligible for stem cell transplant Comparator: bortezomib + melphalan + prednisolone Feasibility assessment confirmed the study feasibility in all regions 20
VERIFY FEASIBILITY WITH REALITY Projections underestimated 800 700 600 500 400 300 200 100 0 Enrollment target reached Screened (planned) Enrolled (planned) Screened Enrolled Multiple myeloma patients were provided with comparator, modern drug not yet available for all patients 21
CASE STUDY #3: NSCLC 2 nd line NSCLC patients IMPs: A novel radiopharmaceutical imaging agent for SPECT Targeted therapy Feasibility assessment conducted in the US, Western Europe, Central and Eastern Europe and Latin America 22
CHALLENGES Regulatory questions Coordination Reporting imaging results Standards of care Imaging requirements Patient transportation Patient availability 23
FEASIBILITY FOCUS In-house experts SPECT Radioactive labeling Result reporting CT experience Capacity Imaging Medical Regulatory Logistics Site Patient availability Standards of care Feasibility expert 24
VERIFY WITH REALITY 500 400 300 200 100 0 Screened (planned) Enrolled (planned) Screened Enrolled 25
CONCLUSIONS Feasibility assessment is a complicated and multi-stage process Increasing complexity of studies requires in-depth scientific analysis of potential challenges that takes time Involvement of a multidisciplinary team is recommended at an early stage 26
Thank you! Questions? Feasibility specialist 27
THANK YOU! 28