Abstract 2675
Background
The estimand framework requires a precise definition of the clinical question of interest (estimand) to account for “intercurrent” events, eg in RCC the appearance of second primary malignancies or the start of new therapy. Selection of the appropriate estimand will drive trial design and support discussions about relevant treatment effects, interpretation of study results, and the added value of drugs.
Methods
A cross-industry collaboration of statisticians and clinicians has worked on connecting estimand framework concepts to different applications. Data from previously reported phase 3, placebo-controlled studies S-TRAC (NCT00375674) and PROTECT (NCT01235962) will be used to illustrate the effect of different estimands on adjuvant treatment outcomes in RCC.
Results
Table shows the treatment outcomes for different estimands. Treatment outcomes were similar to the specified primary analysis irrespective of the clinical question asked; however, the studies were not powered to address each of these questions and not all reached statistical significance. The new framework clarifies that different analyses address different questions. The choice of the primary estimand impacts study design and may have regulatory implications. In RCC, considerations as to whether all second primary malignancies or non-disease related deaths should be considered disease-free survival events are required to further specify study objectives and to determine the events needed for the final analysis.Table:
980P
S-TRAC (N = 615) | PROTECT (N = 1538) | |||
---|---|---|---|---|
Clinical question of interest | Number of events | HR (95% CI) | Number of events | HR (95% CI) |
Specific primary analysis – does the drug improve disease-free survival if no patient received therapy? | 257 | 0.76 (0.59, 0.98) | 513 | 0.80 (0.68, 0.95) |
Does the drug improve disease-free survival and delay the start of new therapy? | 282 | 0.77 (0.61, 0.97) | N/A | N/A |
Does the drug improve disease-free survival regardless of whether the patient had received new therapy? | 289 | 0.81 (0.65, 1.02) | 519 | 0.81 (0.68, 0.96) |
Does the drug improve recurrence free survival in no patient had received new therapy? | 233 | 0.78 (0.60, 1.01) | N/A | N/A |
Conclusions
In S-TRAC and PROTECT, there are similar treatment effects irrespective of the estimand selected and the clinical question asked. However, this may not be the case in all trials and considerations should be given to the clinical question of interest during trial design. Dialogue between all stakeholders is required and physicians will play a key role in such discussions to select the appropriate estimand.
Clinical trial identification
NCT003756674 and NCT01235962.
Editorial acknowledgement
David Cope, PhD, of Engage Scientific Solutions and funded by Pfizer.
Legal entity responsible for the study
Pfizer.
Funding
Pfizer.
Disclosure
D.J. George: Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Exelixis; Honoraria (self), Advisory / Consultancy: Bayer; Advisory / Consultancy: Merck; Research grant / Funding (self): Genentech/Roche; Research grant / Funding (self): Novartis; Research grant / Funding (self): Astellas; Research grant / Funding (self): Celldex; Research grant / Funding (self): Acerta; Advisory / Consultancy, Research grant / Funding (self): Janssen; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy, Research grant / Funding (self): Innocrin Pharma; Advisory / Consultancy, Research grant / Funding (self): Bristol-Myers Squibb. M. Casey: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. E. Degtyarev: Full / Part-time employment: Novartis. M.J. Lechuga Frean: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. P. Aimone: Full / Part-time employment: Novartis. A. Ravaud: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: Merck Sharp & Dohme. R.J. Motzer: Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy: Merck; Advisory / Consultancy: Incyte; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): GlaxoSmithKline. All other authors have declared no conflicts of interest.
Resources from the same session
5579 - Quality of informed consent in clinical trials patients
Presenter: Gianluca Catania
Session: Poster Display session 3
Resources:
Abstract
5147 - Patient's rights: Where do we stand?
Presenter: Maja Kozuh
Session: Poster Display session 3
Resources:
Abstract
1279 - The oncology nurse coordinator’s role in a digestive oncology department: Impact on patient and hospital
Presenter: Fouad Awada
Session: Poster Display session 3
Resources:
Abstract
1670 - Nursing model for a breast cancer unit at the Catalan Institute of Oncology
Presenter: Ana Rodriguez-ortega
Session: Poster Display session 3
Resources:
Abstract
3936 - Role of cancer nurse in the prevention and control of acute deterioration for oncohematologic patient
Presenter: Raquel Azor Portolés
Session: Poster Display session 3
Resources:
Abstract
2789 - Standardized nursing care in the department of radiotherapy of a network of cancer centres
Presenter: José Delgado
Session: Poster Display session 3
Resources:
Abstract
4482 - Exploring anxiety, depression and quality of life of ambulatory cancer patients during chemotherapy.
Presenter: Theodoula Adamakidou
Session: Poster Display session 3
Resources:
Abstract
3075 - Implementing a Cancer Survivorship Program for Individuals with Recurrent Breast Cancer
Presenter: Darcy Burbage
Session: Poster Display session 3
Resources:
Abstract
3869 - The perceptions of parents/guardians regarding their child/adolescent’s experience of reflexology or non-specific foot massage The perceptions of parents/guardians regarding their child/adolescents experience of reflexology or non-specific foot massage
Presenter: Patricia Fox
Session: Poster Display session 3
Resources:
Abstract
4064 - Quality of life in survivors of adult haematological malignancies
Presenter: Anita Immanuel
Session: Poster Display session 3
Resources:
Abstract