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
How to read
the results of a clinical trial
• Statistical significance vs clinical relevance
• Different endpoints
• How (and why) to establish the clinical value
How to read
the results of a clinical trial
• Statistical significance vs clinical relevance
• Different endpoints
• How (and why) to establish the clinical value
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
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:10.1093/annonc/mdq266
Ellis LM, et al. J Clin Oncol. 2014;32(12):1277-1280.
Raising the Bar by Defining
Clinically Meaningful Outcomes
Ellis LM, et al. J Clin Oncol. 2014;32(12):1277-1280.
How to read
the results of a clinical trial
• Statistical significance vs clinical relevance
• Different endpoints
• How (and why) to establish the clinical value
Different endpoints of benefit (patients with advanced /
metastatic cancer)
• Overall survival
• Progression-free survival
• Objective response rate
• Quality of life
…
Different ways of reading a result
Presented By Lowell Schnipper at 2016 ASCO Annual Meeting
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: 1404-1411, 2003
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 patient-
reported outcome (PRO).
• The term PRO is proposed as an umbrella term to cover both single dimension and multi-
dimension measures of symptoms, health-
related 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
How to read
the results of a clinical trial
• Statistical significance vs clinical relevance
• Different endpoints
• How (and why) to establish the clinical value
A Simplistic View of Value
Presented By Lowell Schnipper at 2016 ASCO Annual Meeting
ASCO’s Value Framework
Presented By Lowell Schnipper at 2016 ASCO Annual Meeting
Clinical trial results
Regulatory agency approval
Decision about drug price
Use in clinical practice Drug included in
guidelines
Clinical trial results
Regulatory agency approval
Decision about drug price
Use in clinical practice Drug included in
guidelines ASCO value
framework
<br />Elements Included When Developing ASCO’s Framework
Presented By Lowell Schnipper at 2016 ASCO Annual Meeting
Seeking an Association Between Clinical Benefit, Toxicity and Cost
Presented By Lowell Schnipper at 2016 ASCO Annual Meeting
Schnipper LE, et al. J Clin Oncol. 2015;33(23):2563-2577.
Schnipper LE, et al. J Clin Oncol. 2015;33(23):2563-2577.
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):2563-2577.
Schnipper LE, et al. J Clin Oncol. 2015;33(23):2563-2577.
Adverse grade 3-5 events (irrespective of causality) 81% vs 53%
Schnipper LE, et al. J Clin Oncol. 2015;33(23):2563-2577.
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):2563-2577.
32 -10 10 32
Cost!
Cherny NI, et al. Ann Oncol. 2015;26:1547-1573.
Cherny NI, et al. Ann Oncol. 2015;26:1547-1573.
Clinical trial results
Regulatory agency approval
Decision about drug price
Use in clinical practice Drug included in
guidelines ESMO
magnitude of benefit scale
Drug X vs standard treatment: median OS 9.6 months vs 7.4 months (hazard ratio 0.81; 95% CI 0.68-0.96).
Cherny NI, et al. Ann Oncol. 2015;26:1547-1573.
X
Cherny NI, et al. Ann Oncol. 2015;26:1547-1573.
X
X
Clinical trial results
Regulatory agency approval
Decision about drug price
Use in clinical practice Drug included in
guidelines ESMO
magnitude of benefit scale
ASCO value framework
Clinical trial results
Regulatory agency approval
Decision about drug price
Use in clinical practice Drug included in
guidelines ESMO
magnitude of benefit scale
ASCO value framework
Crucial definition of
VALUE
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
