To the Editor: The timely article by Olver and Haines on industry-led versus investigator-led studies in cancer clearly outlines the importance of appropriate trial design.1

However, perhaps one aspect of this critical issue was underemphasised. In cancer trials, overall survival is typically seen as the primary endpoint. In fact, at time of relapse or disease progression, patients are generally treated in a non-uniform manner. In this scenario, treatment is frequently tailored depending on whether the aim of therapy is curative or palliative. Ad-hoc or experimental approaches are used for some patients with relapsed or refractory cancer. Thus, although survival is undoubtedly the most clinically relevant endpoint, the lack of standardisation of treatment at relapse inevitably confounds assessment of the impact of the study drug on survival.

Furthermore, for many tumour types, full evaluation of time-to-event outcomes, such as event-free and overall survival, requires prolonged follow-up, resulting in studies taking many years to be completed.

For these reasons, biomarkers that accurately serve as early surrogate endpoints to predict for clinical outcome are urgently needed. Yet a striking feature of much industry-led trial design is the paucity of correlative laboratory studies and tissue banking to identify and validate new biomolecular endpoints. Such studies are frequently seen as unnecessary and burdensome. By contrast, although investigator-led laboratory studies of novel biomarkers generate much interest from the clinical and scientific community, their resource and cost implications (chiefly data manager support) prevent many centres from participating. Lucrative company-sponsored trials will always take precedence unless state and/or federal initiatives to support investigator-led studies are enacted. Funding research nurses and data managers to help oncology units conduct non-industry trials that are well designed and incorporate laboratory-based biomolecular research would be an important beginning.

In reply: We support Gandhi’s contention about the value that can be added to clinical trials by performing correlative laboratory studies. The investigation of biomarkers as potential surrogate endpoints that may indicate efficacy, or lack thereof, earlier than the prolonged time sometimes required to reach a survival endpoint, is one such example. Such studies are often not funded by industry and the importance of funding these, which yield greater clinical benefit, should be recognised by government and non-government agencies.

It is possible, but very unlikely, that a survival endpoint may be compromised by the lack of a standardised approach to second-line therapies. We believe that if a new first-line agent is associated with a clinically significant improvement in survival, this will be evident irrespective of subsequent therapies used, which will usually yield inferior results to first-line therapies and will most likely be distributed randomly across the treatment arms.

The need for tissue banks as a resource required across trials in all tumours is something that governments could address by funding them as vital clinical research infrastructure. The same applies to data managers for non-industry sponsored trials that are well designed and incorporate laboratory-based research, as Gandhi suggests.