DELAYS IN CLINICAL TRIAL ACTIVATION 

The efficiency of global clinical trials needs to be improved; it often takes a very long time between study set up and the treatment of patients.

"Improving the efficiency of the activation process would speed up the ability to gather scientific knowledge and evaluate its applicability," said Otto Metzger-Filho, MD, a research fellow from the Dana-Farber Cancer Institute in Boston, Massachusetts, in a release. "Most importantly, it would ultimately benefit the many patients who volunteer to participate in clinical trials. This is the only way to improve treatments for patients with cancer," he explained.

There are frequently "significant delays and bottlenecks across all economic and geographical regions" in the various approval stages before a global phase 3 trial can move forward, he noted.

Dr. Metzger-Filho and colleagues analyzed the time it took to set up the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO) trial, a large international phase 3 breast cancer study conducted in 44 countries. Their analysis was published online January 28 in the Oncologist.

In the participating countries, it took an average of 55 days to receive regulatory approval for the ALTTO protocol, and it took an average of 59 days for ethics committees or institutional review board approval.

"As ALTTO is an almost global trial, it allowed researchers to undertake a differential analysis of how long the various approval stages took in different geographic and economic regions," Christoph Zielinski, MD, a spokesperson for the European Society for Medical Oncology (ESMO), said in a statement.

"As expected from previous experience, the durations of time required from one step to the other were not only quite considerable, but also differed from one region to another," said Dr. Zielinski, who is chair of the clinical division of oncology at Medical University Vienna in Austria. "In all regions, a long time elapsed between approval by institutional review boards or ethics committees and the recruitment of the first patient."

He added that this obviously reflects "the long time needed for negotiations between the organizations sponsoring the study and individual hospitals where the study was supposed to be performed, in addition to the time required for drug import regulations and perhaps the timing of initiation visits at individual sites."

Study Details

Of the 44 countries participating in ALTTO, 24 (55%) are in Europe,12 (27%) are in the Asia-Pacific region, 4 (9%) are in South America, 3 (7%) are in North America, and 1 (2%) is in Africa.

Additionally, 28 (64%) are high-income countries, 10 (23%) are upper-middle-income countries, and 6 (13%) are lower-middle-income countries.

The researchers found that the time to regulatory approval varied considerably by region. South America had the longest median interval (236 days), followed by Africa (130 days), Asia-Pacific (62 days), Europe (52 days), and North America (26 days).

The interval from regulatory approval to the first randomized patient was longer in North America (316 days) than in the other regions. The median interval from ethics committee/institutional review board approval to the first randomized patient was longer in South America than in Europe (335 vs 148 days;P = .014).

The time to study activation across economic regions also varied widely. Median time to regulatory approval was significantly longer in upper-middle-income countries (123 days) than in high-income countries (47 days) or lower-middle-income countries (57 days). This difference reached statistical significance between the groups (F = 9.4; P = .001).

The median time spent by regulatory authorities to approve a study protocol amendment was 34 days, which did not differ significantly across economic or geographic regions.

"The ALTTO trial is large and involves many countries," Roberto Labianca, MD, director of the Department of Oncology and Hematology at Ospedali Riuniti di Bergamo, Italy, said in a statement. "In my opinion, however, the findings reported...are similar to those we could observe in trials for the treatment of other cancers with fewer patients."

"The data generated in this new analysis show that regulatory and hospital authorities have to speed up their processes for study approval, as they obviously can constitute a major obstacle for study initiation, data generation, and the translation of study results into everyday high-quality clinical routine for the benefit of patients," added Dr. Labianca, who is also a spokesperson for ESMO.

This trial was sponsored by GlaxoSmithKline. Several coauthors report relationships with industry, as detailed in the paper.

Oncologist. Published online January 28, 2013. Abstract