GRACE :: Cancer Basics


prospective study

Dr West

Retrospective Data and Real World Evidence: The Poor Stepchild of Clinical Trials?


EvidenceMany physicians worship evidence-based medicine, which is generally a very good practice that ensures that medical practice isn’t dictated by our biases and assumptions but rather on interventions that we have proven show benefits that exceed their anticipated risks.  The optimal way to confirm value of an intervention is by a prospective randomized clinical trial, which is when we enroll a population of patients with the same general disease condition, ideally with no or few other significant medical issues that might cloud the interpretation of what the study intervention is doing, and then randomize them to either pursue what we’d consider the best current practice or an experimental approach that might be better but might also be no better, or even worse.  Other clinical trials may be smaller and may not randomize patients, but they all share a specific list of enrollment criteria, both things that are required in the potential participants (inclusion criteria) and other things that are specifically forbidden (exclusion criteria) to ensure that the study group is reasonably homogeneous.

Cancer treatments are essentially invariably approved on the basis of prospective clinical trials, most often randomized phase 3 trials (large studies of standard vs. investigational strategy), and this gives us confidence that these new approaches are effective.  Aside from the problem that this denies patients who are older and potentially sicker from the opportunity to participate in trials and receive new treatments that may be beneficial, this approach also leaves us wondering whether the treatments proven to help clinical trial candidates are as safe and beneficial for the teeming masses of other people who have complicating issues that would have disqualified them from the trials with such patients.  For example, the trial comparing the immunotherapy Keytruda (pembrolizumab) to standard combination chemotherapy as first line treatment for patients with high level expression of the protein PD-L1 on their tumor cells (a biomarker associated with a higher chance of benefit from immunotherapy) excluded patients who are unable to work or are in bed >50% of the time (performance status of 2 or higher — see here for more discussion), which is a significant minority of patients with advanced non-small cell lung cancer).  We might presume that more frail patients with high PD-L1 expression also do very well with Keytruda, but we can’t know that from the evidence we have.   Because sicker patients don’t have as strong an immune system as more fit patients, immunotherapy may not be as effective as we’d hope. In fact, my  limited experience of treating frail patients with Keytruda or other, similar immunotherapy agents has been quite disappointing, even when the patient has high PD-L1 expression that would lead us to be very hopeful of an excellent chance to respond well. 

Continue reading

Ask Us, Q&A
Cancer Basics Expert Content



GRACE Cancer Video Library - Lung Cancer Videos




2015 Acquired Resistance in Lung Cancer Patient Forum Videos


Join the GRACE Faculty

Lung/Thoracic Cancer Blog
Breast Cancer Blog
Pancreatic Cancer Blog
Bladder Cancer Blog
Head/Neck Cancer Blog
Kidney Cancer Blog

Subscribe to the GRACEcast Podcast on iTunes


Email Newsletter icon, E-mail Newsletter icon, Email List icon, E-mail List icon

Subscribe to
   (Free Newsletter)

Other Resources


Biomedical Learning Institute