Come leggere i risultati di uno studio clinico How to read the results of a clinical trial

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1 Come leggere i risultati di uno studio clinico How to read the results of a clinical trial Massimo Di Maio SCDU Oncologia Medica, AO Mauriziano, Torino Dipartimento di Oncologia Università di Torino massimo.dimaio@unito.it

2 How to read the results of a clinical trial Statistical significance vs clinical relevance Different endpoints How (and why) to establish the clinical value

3 How to read the results of a clinical trial Statistical significance vs clinical relevance Different endpoints How (and why) to establish the clinical value

4 Clinical relevance: for whom? For investigators, who design, conduct and interpret the results of a clinical trial For scientific societies and journals, that should pretend a critical evaluation of presented results For regulatory agencies, that have to decide about authorization for clinical use of drugs For clinicians, who, based on the results of available trials, should make treatment decisions in clinical practice For patients, who are candidates to receive treatment in clinical practice

5 Size of effect! If a new treatment is to be introduced into clinical practice, it should not be enough to show that it is better than the standard therapy, regardless of the size of its effect. Instead, it should be necessary to demonstrate that the effect is clinically worthwhile, meaning as large as or larger than a specified threshold representing the minimal clinically worthwhile effect. Floriani I, Garattini S, Torri V Ann Oncol 2010 doi: /annonc/mdq266

6 Raising the Bar by Defining Clinically Meaningful Outcomes Ellis LM, et al. J Clin Oncol. 2014;32(12):

7 Ellis LM, et al. J Clin Oncol. 2014;32(12):

8 How to read the results of a clinical trial Statistical significance vs clinical relevance Different endpoints How (and why) to establish the clinical value

9 Different endpoints of benefit (patients with advanced / metastatic cancer) Overall survival Progression-free survival Objective response rate Quality of life

10 Different ways of reading a result Presented By Lowell Schnipper at 2016 ASCO Annual Meeting

11 Regular approval is based on end points that demonstrate that the drug provides a longer life, a better life, or a favorable effect on an established surrogate for a longer life or a better life. Johnson JR, Williams G, Pazdur R Endpoints and US FDA approval of oncology drugs J Clin Oncol 21: , 2003

12 Patient-reported outcomes Any outcome evaluated directly by the patient himself and based on patient s perception of a disease and its treatment(s) is called patientreported outcome (PRO). The term PRO is proposed as an umbrella term to cover both single dimension and multidimension measures of symptoms, healthrelated quality of life, health status, adherence to treatment, satisfaction with treatment, etc. European Medicines Agency, 2005 REFLECTION PAPER ON THE REGULATORY GUIDANCE FOR THE USE OF HEALTH RELATED QUALITY OF LIFE (HRQL) MEASURES IN THE EVALUATION OF MEDICINAL PRODUCTS

13 How to read the results of a clinical trial Statistical significance vs clinical relevance Different endpoints How (and why) to establish the clinical value

14 A Simplistic View of Value Presented By Lowell Schnipper at 2016 ASCO Annual Meeting

15 ASCO s Value Framework Presented By Lowell Schnipper at 2016 ASCO Annual Meeting

16 Clinical trial results Regulatory agency approval Decision about drug price Drug included in guidelines Use in clinical practice

17 Clinical trial results Regulatory agency approval Decision about drug price Drug included in guidelines ASCO value framework Use in clinical practice

18 <br />Elements Included When Developing ASCO s Framework Presented By Lowell Schnipper at 2016 ASCO Annual Meeting

19 Seeking an Association Between Clinical Benefit, Toxicity and Cost Presented By Lowell Schnipper at 2016 ASCO Annual Meeting

20 Schnipper LE, et al. J Clin Oncol. 2015;33(23):

21 Drug X vs standard treatment: Improvement in median OS 9.6 vs 7.4 months (30%) = 32 Schnipper LE, et al. J Clin Oncol. 2015;33(23):

22 Schnipper LE, et al. J Clin Oncol. 2015;33(23):

23 Adverse grade 3-5 events (irrespective of causality) 81% vs 53% Schnipper LE, et al. J Clin Oncol. 2015;33(23):

24 Adverse grade 3-5 events (irrespective of causality) 81% vs 53% QoL maintained, delayed symptom worsening, delayed functional status deterioration Schnipper LE, et al. J Clin Oncol. 2015;33(23):

25 Cost! Schnipper LE, et al. J Clin Oncol. 2015;33(23):

26 Cherny NI, et al. Ann Oncol. 2015;26:

27 Cherny NI, et al. Ann Oncol. 2015;26:

28 Clinical trial results Regulatory agency approval Decision about drug price ESMO magnitude of benefit scale Drug included in guidelines Use in clinical practice

29 Drug X vs standard treatment: median OS 9.6 months vs 7.4 months (hazard ratio 0.81; 95% CI ). X Cherny NI, et al. Ann Oncol. 2015;26:

30 X X Cherny NI, et al. Ann Oncol. 2015;26:

31 Clinical trial results Regulatory agency approval Decision about drug price ESMO magnitude of benefit scale ASCO value framework Drug included in guidelines Use in clinical practice

32 Clinical trial results Regulatory agency approval Crucial definition of VALUE ESMO magnitude of benefit scale ASCO value framework Decision about drug price Drug included in guidelines Use in clinical practice

33 Come leggere i risultati di uno studio clinico How to read the results of a clinical trial Massimo Di Maio SCDU Oncologia Medica, AO Mauriziano, Torino Dipartimento di Oncologia Università di Torino massimo.dimaio@unito.it

Choice of appropriate endpoints in clinical trials. Fortunato Ciardiello Second University of Naples

Choice of appropriate endpoints in clinical trials Fortunato Ciardiello Second University of Naples Main primary endpoints used in advanced or metastatic various types of cancers Kiba, J Cancer Sci Ther