Analysis of regional timelines to set up a global phase III clinical trial in breast cancer: the adjuvant lapatinib and/or trastuzumab treatment optimization experience.
OBJECTIVE
This study measured the time taken for setting up the different facets of adjuvant lapatinib and/or trastuzumab treatment optimization (ALTTO), an nternational phase III study being conducted in 44 participating countries.


METHODS
Time to regulatory authority (RA) approval, time to ethics committee/institutional review board (EC/IRB) approval, time from study approval by EC/IRB to first randomized patient, and time from first to last randomized patient were prospectively collected in the ALTTO study. Analyses were conducted by grouping countries into either geographic regions or economic classes as per the World Bank's criteria.


RESULTS
South America had a significantly longer time to RA approval (median: 236 days, range: 21-257 days) than Europe (median: 52 days, range: 0-151 days), North America (median: 26 days, range: 22-30 days), and Asia-Pacific (median: 62 days, range: 37-75 days). Upper-middle economies had longer times to RA approval (median: 123 days, range: 21-257 days) than high-income (median: 47 days, range: 0-112 days) and lower-middle income economies (median: 57 days, range: 37-62 days). No significant difference was observed for time to EC/IRB approval across the studied regions (median: 59 days, range 0-174 days). Overall, the median time from EC/IRB approval to first recruited patient was 169 days (range: 26-412 days).


CONCLUSIONS
This study highlights the long time intervals required to activate a global phase III trial. Collaborative research groups, pharmaceutical industry sponsors, and regulatory authorities should analyze the current system and enter into dialogue for optimizing local policies. This would enable faster access of patients to innovative therapies and enhance the efficiency of clinical research.
Division of Women's Cancers, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey Building 1238, Boston, MA 02215, USA. otto_metzger@dfci.harvard.edu
Otto
O
Metzger-Filho
Evandro
E
de Azambuja
Ian
I
Bradbury
Kamal S
KS
Saini
José
J
Bines
Sergio D
SD
Simon
Veerle Van
VV
Dooren
Gursel
G
Aktan
Kathleen I
KI
Pritchard
Antonio C
AC
Wolff
Ian
I
Smith
Christian
C
Jackisch
Istvan
I
Lang
Michael
M
Untch
Frances
F
Boyle
Binghe
B
Xu
Jose
J
Baselga
Edith A
EA
Perez
Martine
M
Piccart-Gebhart
D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D005260:Female; D006801:Humans; D007391:International Cooperation; D000077341:Lapatinib; D015337:Multicenter Studies as Topic / Q000379:methods*; D011799:Quinazolines / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D013997:Time Factors; D000068878:Trastuzumab
D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; D000077341:Lapatinib; D000068878:Trastuzumab