Small-cell lung cancer: Patients included in clinical trials are not representative of the patient population as a whole

Unité d'Oncologie Médicale, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France.
Annals of Oncology (Impact Factor: 7.04). 08/1999; 10(7):809-15. DOI: 10.1023/A:1008399831512
Source: PubMed


To determine the clinical characteristics of the subpopulation of patients not included in clinical trials, their outcome, and the reasons for their ineligibility and non-participation.
We studied 57 patients (out of 178 consecutive patients with SCLC), who were not included in any of the three successive clinical trials completed at our center during the study period. We also compared 37 patients excluded from the largest clinical trial to their 73 included counterparts.
Reasons for ineligibility (n = 53) included low Karnofsky index (n = 17), advanced age (n = 12), non-feasible long-term follow-up (n = 12), previous history of cancer (n = 8), contraindication for anthracyclines (n = 5), and other medical reasons (n = 11). Only four eligible patients were not included in the trials. As compared to patients included in the studies, non-included patients had a significantly lower Karnofsky index, were older, presented more frequently with metastatic disease, and had a lower response rate to treatment and a shorter survival. However, exclusion from the trial was not an independent prognostic factor by multivariate analysis.
Selection biases were unlikely in the three trials, based on the high ratio of included/eligible patients. However, the subgroup of patients included in the trials was not representative of the patient population as a whole because of restrictive eligibility criteria. Results from published clinical trials to the overall population should be extrapolated only with caution. We suggest that the proportion and major characteristics of ineligible and non-participating patients be mentioned in any publication of a clinical trial.

Download full-text


Available from: Vincent Cottin, Oct 01, 2015
9 Reads
  • Source
    • "Research shows that clinicians often adopt stringent, idiosyncratic criteria when selecting the patients to whom they offer trials, over and above the criteria delineated in trial protocols. In particular, some clinicians only select patients with even better health status and prognosis than demanded by the protocol (Antman et al, 1985; Hjorth et al, 1992; Rahman et al, 1997; Cottin et al, 1999; Siminoff et al, 2000) or choose not to offer trial participation on putative compassionate grounds (Fayter et al, 2007). Clinicians may hesitate to inform patients of trials, based on their own attitudes and beliefs about a patient's willingness to participate, ability to understand the trial, or adhere to the protocol (EDICT, 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Patient accrual into cancer clinical trials remains at low levels. This survey elicited attitudes and practices of cancer clinicians towards clinical trials. The 43-item Clinicians Attitudes to Clinical Trials Questionnaire was completed by participants in an intervention study aimed at improving multi-disciplinary involvement in randomised trials. Responses from 13 items were summed to form a research-orientation score. Eighty-seven clinicians (78%) returned questionnaires. Physicians, more often than surgeons, chose to prioritise prolonging a patient's life, recruited ≥50% of patients into trials and attended more research-focussed conferences. Clinicians at specialist centres were more positive about trials with no-treatment arms than those at district general hospitals, more likely to believe clinician, rather than patient reluctance to participate was the greater obstacle to trial accrual, and preferred national and international to local recognition. Clinicians belonging to breast and colorectal teams were less disappointed about not enrolling patients in trials and more accepting of no-treatment arm trials. Research orientation was higher in physicians than surgeons and higher in specialist centres than district hospitals. This study provides greater understanding of clinicians' attitudes to trials. Results have been used to inform training interventions for clinicians targeting the problem of low and selective accrual.
    British Journal of Cancer 05/2011; 104(10):1535-43. DOI:10.1038/bjc.2011.119 · 4.84 Impact Factor
  • Source
    • "Importantly , all these patients were treated with intensive chemotherapy , on locally developed protocols , except one patient who died prior to starting therapy . Other studies have also concluded that patients in clinical trials are not representative of the patient population as a whole ( Cottin et al , 1999 ; Mengis et al , 2003 ) . Mengis et al ( 2003 ) evaluated recruitment of all patients with a diagnosis of AML who were referred to their centre over a 10 - year period ; during that time , five clinical trial protocols were available to the 215 patients referred to their tertiary referral centre . "
    [Show abstract] [Hide abstract]
    ABSTRACT: This study assessed the recruitment to an acute myeloid leukaemia (AML) trial (AML15) in a single centre, evaluated whether outcome was influenced by trial entry and whether the trial population could be considered representative of all AML patients by retrospective comparison of patient characteristics, trial entry and outcome for 81 consecutive patients (<60 years). All patients were considered for trial entry, however the trial was not offered to 12 (15%) patients. These patients had a worse outcome than the 69 (85%) patients that were invited to participate (P = 0.04). Sixteen patients (23%) invited to participate in the trial declined and were treated on equivalent protocols. These patients had a similar outcome to those who accepted entry into the trial (P = 0.2). These results suggested that physicians exert a selection bias when evaluating patients for trial entry. Thus the overall survival estimates generated from large phase III trials may indicate that the outcome for patients with AML is better than the outcome experienced in the 'real' world. Furthermore, patients who are considered appropriate for randomization into a trial, but decline entry, experience a similar outcome to those treated on trial when treated in an equivalent manner.
    British Journal of Haematology 02/2009; 145(1):40-4. DOI:10.1111/j.1365-2141.2008.07561.x · 4.71 Impact Factor
  • Source
    • "Second, the models were based on expert opinion, which can differ somewhat from real practices. Third, data taken from clinical trials are unrepresentative, in terms of the patient population and management practices (Cottin et al, 1999). Finally, the management of lung cancer is becoming more complex, and the emergence of new antimitotic drugs calls for individual analysis of the respective costs of the different phases of patient management, especially those linked to first-line treatments, active second-or third-line treatments, and palliative care; costs must also be analysed according to the stage at diagnosis, which determines the chosen treatment strategy. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate, according to the histologic type and initial stage, the mean cost (MC) of managing patients with lung cancer and the costs of the different management phases. A Markov approach was used to model these costs, based on the management of a representative nation-wide sample of 428 patients with newly diagnosed lung cancer. The 18-month MC ranged from US$ 20 691 (95% CI: 5777-50 380 for diffuse non-small-cell lung cancer (NSCLC) to US$ 31 833 (95% CI: 15 866-64 455) for localised small-cell lung cancer (SCLC); first-line treatment costs ranged from 33.8% of MC for medically inoperable localised NSCLC to 74.6% for diffuse SCLC; second- or third-line treatment costs ranged from 7.8% of MC for surgically treated localised NSCLC to 32% for locally advanced NSCLC; and the cost of palliative care ranged from 9.1% of MC for locally advanced NSCLC to 39.9% for medically inoperable localised NSCLC. The cost of first-line chemotherapy and the percentage of actively treated patients impacted more on MC than did the cost of second- or third-line chemotherapy regimens or the cost of palliative care. In conclusion, this model provides a robust economic analysis of the cost of lung cancer management, and will be useful for assessing the economic consequences of future changes in patient management.
    British Journal of Cancer 02/2004; 90(2):397-402. DOI:10.1038/sj.bjc.6601547 · 4.84 Impact Factor
Show more