Clinical Oncology 27 (2015) 542e544 Contents lists available at ScienceDirect
Clinical Oncology journal homepage: www.clinicaloncologyonline.net
Letters
Screening Criteria in Breast Cancer Trials: Are They Too Restrictive? Sir d Evidence-based medicine is the cornerstone of modern clinical practice and is of upmost importance in trials of anticancer agents. As the results of randomised controlled trials provide the basis for changes in clinical practice, it is important that patients entering such studies represent the population to which the results are ultimately applied. Inclusion and exclusion criteria determine whether this is the case. We evaluated 1000 consecutive patients, registered on our Breast Cancer Research Unit database between March 2009 and October 2013, who were initially deemed eligible for entry into a clinical study to ascertain the rates and causes of subsequent exclusion from the clinical trial after further screening tests. The reason for a patient’s exclusion from the study was ascertained. Studies were categorised into drug, non-drug, commercial and academic. Overall, 27 patients were identified as ‘screening fails’, a 6.3% failure rate of those consenting to all studies. All of these ‘screening fails’ were noted in drug studies, with 24 of them (88.9%) in commercial studies, the difference compared with the non-commercial studies being significantly different (t ¼ 12.27, P < 0.001). The screening failure rate was significantly higher (34.2%) in commercial drug studies compared with 2.2% in non-commercial drug studies (t ¼ 7.23, P < 0.001). The most common cause of ‘screen failure’ was abnormal liver function tests. We assessed the reasons for exclusion from the studies and felt that for 14 patients (52%) we would have been happy to treat the patients with the trial protocol outside of a study, as safety and efficacy would not have been compromised.
One of the important aspects of randomised control trials is ensuring that they are generalisable, i.e. that the result of the trial can be applied to the ‘real world’ population. There is a risk that by excluding patients after screening tests that this generalisability is being lost. It is also important to ensure that patients considering entry into a clinical trial are offered accurate information on the screening process. Most cancer drug studies are conducted in patients with metastatic disease and the timing of entry will usually be when they have either recently been diagnosed or have disease that has progressed through a previous line of therapy. This can be a difficult time and the consideration of a clinical study, often with the potential hope that a new drug offers, will require some thought from the patient. The patient information sheets often describe the screening process but fail to give any estimate of the chances of an individual patient failing to meet the eligibility criteria for study entry once they have consented to the trial. We feel that consideration should be given to making eligibility criteria less restrictive in commercial drug studies and described better in the final manuscript, as should details of excluded patients. Patient information sheets should make it clear that despite consent to the trial, a relatively high proportion of patients may become ineligible after screening tests. D.K. Woolf*, D.W. Miles*, P.D. Nathany, E. Windmill*, A. Makris* * Breast Cancer Research Unit, Mount Vernon Cancer Centre, Northwood, UK y Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood, UK
http://dx.doi.org/10.1016/j.clon.2015.04.006 Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Stereotactic Body Radiotherapy for Pulmonary Metastases Sir d Hanna and Landau’s article [1] on the use of stereotactic body radiotherapy (SBRT) in oligometastatic disease provides a useful critique of this uncertain clinical entity. However, we question their suggestion that ‘a highly effective boost treatment to 90% of malignant disease . might give additional value to systemic therapy’. It is illogical to think that ablation of a few asymptomatic and non-life-threatening metastases is likely to change overall
survival and there is no randomised trial evidence of any local treatment of metastases to support this view. They are incorrect in stating that the PULMiCC trial (Pulmonary Metastasectomy in Colorectal Cancer) is ‘recently completed’. The feasibility study has been completed and the full trial is now open to recruitment [2]. They also support the use of SABR in ‘oligometastatic’ non-small cell lung cancer with flawed evidence. They cite an
Clinical Oncology journal homepage: www.clinicaloncologyonline.net
Letters
Screening Criteria in Breast Cancer Trials: Are They Too Restrictive? Sir d Evidence-based medicine is the cornerstone of modern clinical practice and is of upmost importance in trials of anticancer agents. As the results of randomised controlled trials provide the basis for changes in clinical practice, it is important that patients entering such studies represent the population to which the results are ultimately applied. Inclusion and exclusion criteria determine whether this is the case. We evaluated 1000 consecutive patients, registered on our Breast Cancer Research Unit database between March 2009 and October 2013, who were initially deemed eligible for entry into a clinical study to ascertain the rates and causes of subsequent exclusion from the clinical trial after further screening tests. The reason for a patient’s exclusion from the study was ascertained. Studies were categorised into drug, non-drug, commercial and academic. Overall, 27 patients were identified as ‘screening fails’, a 6.3% failure rate of those consenting to all studies. All of these ‘screening fails’ were noted in drug studies, with 24 of them (88.9%) in commercial studies, the difference compared with the non-commercial studies being significantly different (t ¼ 12.27, P < 0.001). The screening failure rate was significantly higher (34.2%) in commercial drug studies compared with 2.2% in non-commercial drug studies (t ¼ 7.23, P < 0.001). The most common cause of ‘screen failure’ was abnormal liver function tests. We assessed the reasons for exclusion from the studies and felt that for 14 patients (52%) we would have been happy to treat the patients with the trial protocol outside of a study, as safety and efficacy would not have been compromised.
One of the important aspects of randomised control trials is ensuring that they are generalisable, i.e. that the result of the trial can be applied to the ‘real world’ population. There is a risk that by excluding patients after screening tests that this generalisability is being lost. It is also important to ensure that patients considering entry into a clinical trial are offered accurate information on the screening process. Most cancer drug studies are conducted in patients with metastatic disease and the timing of entry will usually be when they have either recently been diagnosed or have disease that has progressed through a previous line of therapy. This can be a difficult time and the consideration of a clinical study, often with the potential hope that a new drug offers, will require some thought from the patient. The patient information sheets often describe the screening process but fail to give any estimate of the chances of an individual patient failing to meet the eligibility criteria for study entry once they have consented to the trial. We feel that consideration should be given to making eligibility criteria less restrictive in commercial drug studies and described better in the final manuscript, as should details of excluded patients. Patient information sheets should make it clear that despite consent to the trial, a relatively high proportion of patients may become ineligible after screening tests. D.K. Woolf*, D.W. Miles*, P.D. Nathany, E. Windmill*, A. Makris* * Breast Cancer Research Unit, Mount Vernon Cancer Centre, Northwood, UK y Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood, UK
http://dx.doi.org/10.1016/j.clon.2015.04.006 Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Stereotactic Body Radiotherapy for Pulmonary Metastases Sir d Hanna and Landau’s article [1] on the use of stereotactic body radiotherapy (SBRT) in oligometastatic disease provides a useful critique of this uncertain clinical entity. However, we question their suggestion that ‘a highly effective boost treatment to 90% of malignant disease . might give additional value to systemic therapy’. It is illogical to think that ablation of a few asymptomatic and non-life-threatening metastases is likely to change overall
survival and there is no randomised trial evidence of any local treatment of metastases to support this view. They are incorrect in stating that the PULMiCC trial (Pulmonary Metastasectomy in Colorectal Cancer) is ‘recently completed’. The feasibility study has been completed and the full trial is now open to recruitment [2]. They also support the use of SABR in ‘oligometastatic’ non-small cell lung cancer with flawed evidence. They cite an
