A study published in The Oncologist emphasizes the critical need for regulatory authorities, pharmaceutical clinical study sponsors, collaborative research groups and other interests to work together to expedite study approval for clinical trials in cancer research on a global scale. The study highlighting the need to avoid unnecessary delays in approving clinical trials.[1]

In their research paper Otto Metzger Filho, MD, Dana-Farber Cancer Institute, and colleagues, investigated the time that elapsed between the various regulatory steps, including approval from national regulatory authorities, ethics committees and review boards within participating institutions, before researchers could start treating patients in the Phase III ALTTO trial which includes over 8,300 women with early-stage breast HER2-positive cancer in 44 countries. The ALTTO study aims to evaluate whether the drug lapatinib is effective in helping patients with early breast cancer survive longer after surgery without their cancer returning. Patients were enrolled in the trial between 2007 and 2011, and will be followed for a total of 10 years.

Different aspects
The research team evaluated different aspects of ALTTO activation across different geographic and economic regions, measuring time intervals for regulatory approval, ethics approval, protocol amendments, and times for patient enrollment. Although some of these time periods did vary in different regions, the study?s primary finding was that significant delays and bottlenecks occurred across all regions.

?Improving the efficiency of the activation process would speed up the ability to gather scientific knowledge and evaluate its applicability,? Metzger Filho explained. ?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. While the study?s focus on ALTTO means its findings cannot be generalized to make definitive statements about a region?s clinical trial proficiency, its main finding of consistently lengthy timetables should spark a global discussion about the need to improve the efficiency of all cancer trials,? he noted.

The European Society of Medical Oncology (ESMO) welcomed the study’s results. Professor Christoph Zielinski, M.D., Chair, Clinical Division of Oncology, Medical University Vienna, Austria, and spokesperson for ESMO, the ESMO, described the importance of these findings: ?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. 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.?

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Regulatory Study
The study showed that the median approval time was longest in South America, where the regulatory processes took 236 days compared to 52 days in Europe, 26 days in North America and 62 days in the Asia-Pacific. Overall, it took an average of 55 days for national regulators to give their approval to the trial protocol, 59 days for approval by ethics committees or institutional review boards, and 169 days from the ethics committee or institutional review board approval until the treatment of the first patient, the study shows.

?In all regions, a long time elapsed between approval by institutional review boards or ethics committees and the recruitment of the first patient,? Zielinski noted. ?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. Once trials were approved and started, recruitment was swift and very effective in almost all geographic regions,? he explained. ?This demonstrates the high interest of investigators and the high relevance of the trials for patients.?

Large scale clinical trials, especially those that are based on collaborations among cooperative groups, such as the ALTTO study, help oncologists make significant improvements in therapy and modify the standard of care, said Roberto Labianca, M.D., Director, Department of oncology and hematology, Ospedali Riuniti di Bergamo, Italy. ?Unnecessary delays in the approval of clinical trials mean patients can miss the advantages of a new active drug, a new combination of drugs or a novel therapeutic strategy, because oncologists will be compelled to use traditional and potentially sub-optimal treatments,? he said.

Hospitals and regulatory authorities: major obstacle
?The ALTTO trial is large, and involves many countries. In my opinion, however, the findings reported in the paper 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,? Labianca observed.

?Countries should undertake major efforts to set limits on the timeframe for regulatory assessment of clinical trial protocols, as well as the minimum speed of the various steps after a positive vote by individual institutional authorities,? Zielinski added. ?Only then will we be able to speed up the availability of results of clinical trials, which is ever more important at a time when more intricate and promising drugs with more attractive targets for individual malignancies are entering the field of clinical trials.?

?We hope that this study will help investigators in different regions to identify the bottlenecks in activating multinational trials and to address the problem of clinical trial participation,? Metzger Filho noted.

Expedite and harmonize
?These findings emphasize the obvious need to expedite, and harmonize, the process for review and approval of new trials across continents. Large studies are increasingly being conducted on an international basis. The delays in implementation of these trials not only deprive patients of access to drugs, but delay their completion and ultimately, regulatory approval. No one wins, least of all the patient,? concluded Bruce Chabner, M.D. Editor-in-Chief of The Oncologist and Director of Clinical Research, MGH Cancer Center, Massachusetts General Hospital.

[1] Metzger-Filho O, De Azambuja E, Bradbury I et al. Analysis of Regional Timelines to Set Up a Global Phase III Clinical Trial in Breast Cancer: The ALTTO Experience. The Oncologist doi: 10.1634/theoncologist.2012-0342 [epub ahead of print on January 28, 2013]

Photo 1:Otto Metzger Filho, MD, Photo credit:MD, Dana-Farber Cancer Institute. Photo 2: Roberto Labianca, M.D., Director, Department of oncology and hematology, Ospedali Riuniti di Bergamo, Italy.
Photo Credit: ESMO.

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