1 / 42

To share or not to share It’s your call !

To share or not to share It’s your call !. Are we living in Splendid Isolation ?. Island of Neutropenia. Michael Angelo Petrone. How did this idea start ?. AITL a remarkable response to Thalidomide. Clinical Trials - Problems . Selectivity Bias Not good for ‘VULNERABLE’ groups

marie
Télécharger la présentation

To share or not to share It’s your call !

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. To share or not to shareIt’s your call ! Are we living in Splendid Isolation ? Island of Neutropenia. Michael Angelo Petrone

  2. How did this idea start ? • AITL a remarkable response to Thalidomide

  3. Clinical Trials - Problems • Selectivity • Bias • Not good for ‘VULNERABLE’ groups • children, elderly, pregnant, developing world • risk of OBSOLESCENCE • Regulation • Bureaucracy • Cost

  4. CASE REPORTS - Problems • CASE REPORTS • POSITIVE OUTCOME PUBLICATION BIAS • EDITORS DISLIKE CASE REPORTS • SOFT PUBLICATIONS • DEVALUE THE JOURNAL • HIGHLY SELECTIVE • CANNOT BE EASILY/REGULARLY UPDATED • NOT UNIFIED INTO A SINGLE DATABASE • UNSTRUCTURED

  5. CONVENTIONAL REGISTRIES - issues • Denominator is all patients with the disease in a defined territory. • Disease incidence, prevalence and outcomes on a population wide basis • Most of the effort (99%) in data collection is ‘uninteresting’ with respect to investigational therapies. • Global scope is essential.

  6. Comparison table

  7. Summary so far

  8. Summary so far • Existing sources of data are flawed. • Inadequate for clinical needs - especially for patients with • rare diseases • relapsed/resistant disease • children • pregnant • elderly • diseases specific to developing countries

  9. Evolution or Revolution If I asked my customers what they wanted, they would have said: “FASTER HORSES” Henry Ford

  10. INVENTION “You look at things and ask - Why ? But I dream of things that never were, and ask - Why not ?” George Bernard Shaw

  11. CICERO MARCUS TULLIUS CICERO

  12. CICERO • C ollection • I nvestigational • C ase-reports • E lectronic • R egistry • O utcomes

  13. CICERO - Key features 1 • Database/Journal to record outcome data to Investigational Therapies of Interest • Using the Internet to Record Existing Work Systematically • Open Access • Global

  14. CICERO - Key Features 2 • Peer Reviewed: Data And Contributors • Trustworthy • Professionally controlled • No vested interests • Not-for-profit • Low Cost • Low Bureaucracy • Easy to Update/Edit • Free from publication bias

  15. Free from Publication Bias ?? PRE-TREATMENT APPROVAL ‘INTENTION TO PUBLISH’ ANALYSIS

  16. The Process

  17. THE PROCESS • Suitable case arises • Clinician obtains informed consent • Clinician submits case for pre-approval • Approval given on condition that: • regular outcome updates at agreed intervals • until agreed endpoint • outcomes may be positive, negative or neutral • reports of any adverse effects • patient identity anonymised

  18. Comparison table

  19. CICERO versus CONVENTIONAL REGISTRIES • CONVENTIONAL REGISTRIES • Denominator is all patients with the disease in a defined territory. • Disease incidence, prevalence and outcomes on a population wide basis • Most of the effort (99%) in data collection is ‘uninteresting’ with respect to investigational therapies. • CICERO • Denominator is the treatment episode. • Concentrate on the first hundreds/ one thousand/ two thousand patients treated worldwide with a new therapy. • Global scope is essential.

  20. CICERO versus RCT’s • CICERO is not an alternative to RCT’s • Data quality CICERO < RCT’s • Selectivity CICERO < RCT’s • REPRESENTATIVENESS • CICERO > RCT’s ?

  21. Where does CICERO fit in ? CICERO PHASE 1 AND 2 EXPERT OPINIONS CASE REPORTS PHASE 3 IV -> -> -> III -> -> -> II > -> -> I EVIDENCE LEVEL

  22. WHAT IS A SUITABLE CASE ? • INVESTIGATIONAL THERAPY AVAILABLE • DRUG - UNLICENCED/OUTSIDE OF LICENSE • PATENT EXPIRED • NON-DRUG BIOTHERAPY, IMMUNOTHERAPY, CELLULAR • VACCINE, COMBINATION • NO CLINICAL TRIAL AVAILABLE LOCALLY • PATIENT REFUSES ENTRY TO TRIAL • PATIENT EXCLUDED FROM TRIAL • PATIENT FULLY INFORMED AND CONSENTED

  23. Real Examples • Response rate for: • Mycophenolate in resistant ITP • Match patients with following characteristics: • HCL female; age 58; DCF Resistant • What treatments have been tried and what were the crude response rates ? • Side effects of MabCampath: age > 70 yrs

  24. Early detection of adverse events • Existing systems have problems • Case reports and case series (publication bias) • Clinical trials (selection bias, power) • Yellow card systems • (poor compliance, geographically restricted) • We need a system which can: • Detect infrequent but serious adverse events • Detect them early – (1000-2000 exposures) • Detect them wherever they happen (global coverage) • Offers incentives to contribute • Targets new drugs, and new indications.

  25. POTENTIAL USES • CRUDE OUTCOME RATES • EARLY DETECTION OF ADVERSE EVENTS • FOR THE FUTURE • NON-HAEMATOLOGICAL MALIGNANCY • NON-MALIGNANT CONDITIONS • NEW INTERVENTIONAL PROCEDURES • NEW SURGICAL TECHNIQES • CELLULAR THERAPIES • SPECIAL GROUPS • RARE DISEASES, CHILDREN, PREGNANCY, ELDERLY

  26. CICERO and RARE DISEASES • Clinical Trialists tend to ignore rare diseases • But in a way - all diseases are becoming rare ! • AML is now stratified - for instance. • Lymphoma is becoming stratified according to: • New DIAGNOSTIC modalities • Application of PROGNOSTIC INDICATORS • Therapy is becoming ‘tailored’ • MRD STATUS • RATE OF ACHIEVEMENT OF CR • RATE OF ATTAINMENT OF PET NEGATIVITY

  27. GIVE ME AN EXAMPLE ! • IS CLL BECOMING A RARE DISEASE ? • OUR COMMMONEST LPD • SLOW DISEASE • TRIALS LASTING >10 YEARS TOO SLOW NOWADAYS • DIAGNOSIS STRATIFIED A/C PROGNOSTIC INDICATORS • CLINICAL STAGING, WCC DOUBLING TIME, • SERUM MARKERS, CD38, IgVH STATUS, ZAP70 Cytogenetics • TAILORING OF TREATMENT • Drug sensitivity testing, P53, CD38 expression, microarrays • MRD detection by FLOW or BM immunohistochemistry • INVESTIGATIONAL THERAPIES OF INTEREST • Purine analogues, HDMP, MOAB’S, ABMT, ALLOBMT, MiniALLO • Splenic irrad, Radioimmunoconjugates, proteasome inhibitors, anti-angiogenesis agents, cyclin dependent kinase inhibitors (Roscovitine)

  28. What about children, pregnancy and the elderly ? • Paediatricians generally prefer to offer standard therapy or a new investigative therapy - but outside of the confines, and restrictions of a clinical trial. • They are already doing the clinical work of participation in clinical trials, but they are no better off, as they do not record and share the outcome data.

  29. What about children, pregnancy and the elderly ? • New therapies are licensed often excluding these important population groups. • CICERO offers the opportunity to at least partially redeem the situation, gathering information after the event perhaps, but better to do this than nothing at all.

  30. WHY NOW ? • ONLINE TECHNOLOGY NOW MATURE AND ACCEPTED • PROBLEMS WITH TRANSLATION OF RESEARCH • NEW WAYS TO STRATIFY DISEASE • DIAGNOSIS • RESPONSE • NEW MODALITIES OF THERAPY • BUREAUCRACY SURROUNDING • CONDUCT OF CLINICAL TRIALS • PUBLICATION TO PAPER JOURNALS • NEW OPPORTUNITY TO CONTRIBUTE TO THE KNOWLEDGE BASE - WITHOUT THE BUREAUCRACY • THE PROBLEM OF RARE ENTITIES

  31. THE REWARDS • CONTRIBUTING CLINICIANS • A NEW WAY OF CONTRIBUTING TO THE KNOWLEDGE BASE • SERIES OF CASES ( >5 ?) COULD BE REWARDED WITH A CITATION ON MEDLINE OR PUBMED • CME POINTS • REWARDS SCHEME FOR SpR’s • PATIENTS • DECISION SUPPORT TOOL • May help guide treatments for new patients • May help inform design for future RCT’s

  32. POTENTIAL PROBLEMS WITH NEW PROPOSAL • TECHNOLOGY • FUNDING/SUPPORT • MIS-USE OF DATA • MANIPULATION OF INPUT DATA ? • MIS-INTERPRETATION OF DATA • SUB-GROUP ANALYSIS • ETHICS

  33. WHO SHOULD PAY ? • PHARMA INDUSTRY ? • PER CASE ? • PER COMPANY ? • PER INDUSTRY ? • NHS /GOVERNMENT ? • CHARITIES ? • NATIONAL LOTTERY ? • CONTRIBUTORS ?

  34. WHO SHOULD CONTROL IT ? • THE PROFESSION - WHY ? • DATA HAS TO BE TRUSTED • FREE FROM VESTED INTERESTS • IMPLICATIONS • WILL HAVE SIGNIFICANT COSTS • WILL HAVE TO BE PROPERLY REGULATED • WILL REQUIRE CO-OPERATION FROM COMMUNITY • WILL REQUIRE DISCIPLINE

  35. Potential Sanctions for Misuse • Cases/Contributors removed • when input data are inaccurate • when input data are not regularly updated • Cancellation of credits • Editor’s decisions are final ?

  36. CICERO SUMMARY • ONLINE DATABASE • PROFESSIONALLY REGULATED • OUTCOMES TO CASE REPORTS • PUBLICATION PRE-APPROVAL • REGULARLY UPDATED BY ACCREDITED CONTRIBUTORS • DECISION SUPPORT TOOL FOR THE FUTURE • LOW COST TO CONTRIBUTORS AND USERS • NOT-FOR PROFIT • FREE FROM VESTED INTERESTS • LOW BEUREAUCRACY

  37. To Share or not to ShareHow Do We Plead ? • Guilty or Not Guilty

  38. To Share or not to Share • Guilty ? • Misdemeanour or Felony ? • What is the cost of complacency ? • Who has the solution ?

  39. WAITING FOR A MIRACLE • You can either take action or you can wait for a miracle. • Miracles are great - but they are so unpredictable. • The best way to predict the future is to create it. Peter F Druker

  40. CICERO Key Messages • Existing systems for sharing data are inadequate for clinical needs. • The technology to make things better already exists. • You need to declare your support for this type of proposal - otherwise it will not happen.

  41. To share or not to share ?It’s your call ! I’m a clinician Get me out of here !

  42. CICERO your next step • Submit a comment www.CICER.Org • E-mail a friend • Help select a pilot • Give it your support • Advertising • Funding

More Related