Health Services Research
Clinical trial subjects compared to "real world" patients: Generalizability of renal cell carcinoma trials.
Background: While narrow eligibility criteria improve the internal validity of clinical trials, they threaten the generalizability of study findings to real-world populations. How similar is the population of patients receiving treatment for metastatic renal cell cancer (mRCC) to subjects enrolled in pivotal trials? Methods: A retrospective registry of academic (Duke University Health System) and community (ACORN Network) practices was used to compare real world mRCC patients to study subjects in the landmark phase III clinical trials of the new, targeted therapies. Patients were compared to subjects who were treated with the same agent. Results: Of 633 patients in the registry, 438 received sunitinib, sorafenib, temsirolimus, or pazopanib; everolimus and axitinib were not included due to small patient numbers. Registry patients were a mean of 4.6 years older than clinical trial subjects (p <0.0001). With the exception of temsirolimus-treated patients, registry patients had poorer risk disease by MSKCC model (poor: 7.4% vs 2.9%, p<0.0001; favorable: 30.6% vs 43.8%, p=0.0004) and were more likely to have impaired functional status (ECOG >1, 8.4% vs 0.6%, p<0.0001). Applying the eligibility criteria described in the clinical trial manuscripts, 40.0% of patients failed inclusion criteria for the phase III clinical trial testing the drug they received (Table), 9.9% due solely to non-clear cell histology. Conclusions: mRCC patients in “real world” clinical practice are older and sicker than those enrolled in pivotal clinical trials. Over one third of mRCC patients would not have met eligibility criteria for the phase III clinical trial that led to approval of the agent they received. Application of clinical trial findings to dissimilar populations may result in patient harm. Research of mRCC drugs in general populations is needed to guide real world clinical practice.
|Agent used to treat |
mRCC cohort patients
|N||Clinical trial used |
|Patients meeting |
exclusion criteria (%)
|Sunitinib||289||Motzer et al, NEJM 2007||98 (33.9)|
|Sorafenib||59||Escudier et al, NEJM 2007||20 (33.9)|
|Temsirolimus||59||Hudes et al, NEJM 2007||44 (74.6)|
|Pazopanib||31||Sternberg et al, JCO 2010||13 (41.9)|