Comparison of clinical outcomes among cancer patients treated in and out of clinical trials

doi:10.21203/rs.3.rs-2564790/v1

Background. It is unknown if participation in a cancer clinical trial confers clinical benefits to patients. There is not enough scientific evidence in this regard and the available publications are scarce and provide ambiguous and limited information.

Objective. Compare overall and progression-free survival and response to treatment among those who met the eligibility criteria and accepted to participate and those who refused to participate in cancer clinical trials.

Methods. An observational cross-sectional study with an analytical component was carried out, which included patients diagnosed with cancer who participated in phase III clinical trials and patients who, being eligible, refused to participate. The patients were cared for at the National Institute of Cancerology in Colombia between 2019 and 2022. Analysis of differences in proportions and means of sociodemographic and clinical variables was included; overall survival and progression-free survival time were described and the survival curves between groups were compared. Variables related to survival were determined using a Cox regression model and Hazard Ratios were calculated.

Results. 112 patients were included (51 participants and 61 refusers). Median progression-free survival for participants was 18.1 months (95%CI 14.0-22.2) vs 24.0 months (95%CI 16.4-31.5) in refusers p=0.23 and median overall survival for participants was 21.9 months (95CI % 17.6-26.1) vs refusers 33.2 months (CI95% 24.0-42.3), for the participating women it was 21.6 months (14.7-28.5 IC95%) vs refusers 22.7 months (9.3-36.0 IC95%) and for the group of participating men was 16.7 months (14.3-19.1 IC95%) and for refusers 32.4 months (25.5-39.3 IC95%). In the Cox proportional hazards model, only ECOG 1 was a better predictor of survival HR 0.48 (95%CI 0.23-0.97) p=0.042.

Conclusion. This investigation found that participation in a clinical trial regarding rejection was associated with improved response rates, with no significant difference in overall or progression-free survival outcomes.

Clinical trials can provide high evidence of the efficacy and safety of new treatments for the treatment of diseases (1) and are required by regulatory agencies for the approval of new drugs, which is conditional on the impact they produce on clinical outcomes. and the quality of life of patients (2).

The gold standard for measuring the efficacy of anticancer drugs, especially in cancer patients with an advanced or metastatic stage, is overall survival (OS) but takes a long time, and additionally, losses to follow-up or censorship of patients make it difficult to measure. Currently, many new drugs are approved based on the improvement of surrogate outcomes that are measured more quickly such as progression-free survival (PFS), response to treatment, and improvement in the patient's quality of life (3) which, together with a palliative benefit in reducing cancer-related symptoms, are elements considered essential for a beneficial therapy for cancer patients (4).

Oncological outcomes that are evaluated in cancer clinical trials are classified as primary when they are patient-centered and include, among others, response to treatment, survival time, and those related to quality of life. Secondary outcomes focus on tumor behavior and its response to treatment, which is assessed through diagnostic imaging or biomarker measurement. The time to evaluate the tumor response generally varies between 90 and 120 days after the start of treatment. Composite outcomes between survival, progression and recurrence are reported in some trials. (5).

During a clinical trial, the participants have the possibility of receiving investigational treatments under a rigorous follow-up of their condition; Therefore, it is assumed that the partipants would obtain better clinical outcomes. There is even a wide perception among doctors and nurses that clinical trials confer benefits to the participants that are superior to those of regular care (6). However, the scientific evidence supporting this claim is scant, weak, and inconclusive. (6, 7). Some studies have reported better clinical outcomes in clinical trial participants than in regular care patients; but these results may not be valid due to a lack of comparability and clear differences between groups, because clinical trial participants must meet previously established eligibility criteria that exclude those with diminished general conditions, greater comorbidities, and poor health functional status (8). It is also possible that those who presented better clinical outcomes were only those assigned to the intervention arm or that they were influenced by psychological aspects such as those presented with the placebo effect, the Hawthorne effect and the "trial effect" (9, 10)(11, 12). We try to make a better comparison of clinical outcomes between the groups, this study included patients who met eligibility criteria to participate in a clinical trial and discriminated between those who agreed to participate and those who refused.

Patients

An observational cross-sectional study with an analytical component was carried out, a sample size was estimated to establish differences in survival at 12 months and response to treatment in patients diagnosed with locally advanced or metastatic cervical cancer and prostate cancer. metastatic patients who participated in phase III clinical trials and in patients who, despite having been eligible, refused to participate. The clinical trials were ongoing and the patients were cared for at the National Institute of Cancerology in Colombia between 2019 and 2022. Cases that presented loss of information were excluded.

This research complied with the guidelines established by the Declaration of Helsinki and the ethical guidelines for biomedical research prepared by the Council for International Organizations of Medical Sciences (CIOMS) and with the parameters established by national regulations, additionally it was approved by the ethic and research committee at the National Cancer Institute. According to the local regulatory frame, it was an investigation without risk, therefore informed consent was not necessary and the results do not contain any data of identification for patients. This research was monitored by an independent monitoring team that verified the validity of the data and information recorded in RedCap (Research Electronic Data Capture).

Statistical analysis

Descriptive statistical methods were used for sociodemographic, clinical and treatment characteristics, absolute and relative frequencies were estimated for categorical variables, measures of central tendency and dispersion were calculated for quantitative variables; Analyzes stratified by participation in clinical trials, type of cancer, and clinical outcomes were used. Tests were used to determine normality and homogeneity of variances. To determine the difference in proportions between groups, the Xi-squared test or Fisher's exact test was used, and the Student's T test was used to determine the difference in means. Overall survival (OS) and progression-free (PFS) time was described graphically and with time-to-event functions, estimated using the Kaplan-Meier method, the survival function and the 95% CI were estimated for the endpoints of time to event. Vital status was verified quarterly for 18 months. Censored data were considered when the follow-up time of a patient ends before death or before completing the observation period, when survival times cannot be accurately established, or when the patient dies from causes unrelated to the event. of interest.

Progression-free and overall survival time was determined from the start date of treatment or the date of randomization, until disease progression or death from any cause. Objective response was assessed using the Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria to determine reduction and/or disappearance of tumor size after treatment. Clinical outcomes of each patient were made quarterly up to an observation period of 18 months or until death.

An exploratory analysis was performed with the exposure variable (participation in clinical trials) and some explanatory covariates such as age, sex, tumor type, tumor stage, metastatic disease, and ECOG. Survival curves were compared and differences between groups were estimated using the log-rank test. To assess the association between participation and survival, a univariate Cox proportional hazards model was used with the calculation of hazard ratios (HRs) and 95% CI. A multivariable model would be used to assess the prognostic value with those covariates that have demonstrated a level of significance with p values less than or equal to 0.05. SPSS was used for data analysis.

Patients

112 patients were included, 51 participants (45.5%) and 61 (54.4%) refusers who were eligible to participate in phase III clinical trials, 62 (55.4%) were women and 50 (44.6%) men. The median age of the participants was 64 years (IQR 30) vs. 61 years (IQR 32) in refusers, 8 women and 16 men participating were older than 65 years. 38.3% of the patients belonged to the subsidized social security system, 93.7% corresponded to socioeconomic strata 1, 2 and 3 and 91.9% had an educational level between primary and secondary. Within the clinical characteristics, 95.5% had a favorable functional status determined by ECOG 1 and 2, the clinical status of the patients was mostly advanced, in stage I and II: 14.2%, stage III: 42.8% and IV: 42.8 % (in Ca of the cervix, stage IVA and IVB were included as IV), with lymph node involvement 56.2% and metastatic state 27.6%. The sociodemographic and clinical characteristics are summarized in Table 1.

Relationship between clinical characteristics and participation in cancer clinical trials

We found a higher proportion of occurrence of non-serious adverse events among the participants 88.2% vs refusers 6.5%, (HR 11.0 IC95% 4.3-28.4), in response to treatment the proportion of patients with disease in progression and stable disease was higher in the refusers vs participants 57.3% and 42.6% vs 31.3% and 31.3% respectively.

On the other hand, in the group of participants the complete response occurred in 14 patients (27.4%) and the partial response in 5 patients (9.8%), while in the group of refusers both were 0%. Both the occurrence of adverse events and the response to treatment were statistically associated with participation in clinical trials (P=0.000). The proportion of patients with disease progression was 28.2% higher among non-participants (HR 0.5 95% CI 0.2-1.1) as well as mortality was 20.0% in rejecters (Table 2). However, there was no statistical association between mortality and participation in clinical trials (HR 0.73 IC95% 0.31-1.71).

Survival

Median progression-free survival for participants was 18.1 months (95%CI 14.0-22.2) vs 24.0 months (95%CI 16.4-31.5) in refusers, Log Rank 1.38, p=0.23 (figure 1) and median overall survival for participants it was 21.9 months (95%CI 17.6-26.1) vs rejecters 33.2 months (95%CI 24.0-42.3) Log Rank 0.21, p = 0.64 (figure 2). In the participating men group the OS was 16.7 months (14.3-19.1 95%CI) and for refusers was 32.4 months (25.5-39.3 95%CI), (figure 3A), for participating women it was 21.6 months (14.7- 28.5 IC95%) vs refusers 22.7 months (9.3-36.0 IC95%) Log Rank 0.47, p = 0.49 (figure 3B). Although the percentage of patients alive at 12 months was higher in the group of participants (86.3% vs 75.4%) and the proportion of patients without progression at 12 months was also higher among the participants (82.0% vs 54.9%).

In the Cox proportional hazards model (Table 3) only ECOG 1 was a significant predictor of survival HR 0.48 (95%CI 0.23-0.97) p=0.042.

Therapies for the treatment of cancer are considered to be beneficial when they prolong survival, when they provide a palliative benefit in reducing symptoms, or when they improve the patient's quality of life. (4). Accordingly, clinical trials seek to achieve an improvement in the efficacy outcomes with respect to standard therapy. (13). The efficacy of a new drug must be determined mainly by obtaining benefits on overall survival, disease-free and progression-free survival time, and to a lesser extent on surrogate outcomes such as the response rate to treatment and the behavior of some tumor markers (14)(15).

Clinical trials must overcome barriers that limit their development; one of the main ones is the recruitment of patients which occurs in 77% and approximately 53% have to extend their duration and only 31% achieve the enrollment goals (16,17). It is estimated that only 3% of cancer patients manage to participate in clinical trials (18) and this low participation is mainly due to the lack of availability of certified hospitals for the development of clinical trials, the rigor in the enrollment of subjects which restricts admission to 3-5% of all subjects submitted to screening (19,20) and by the refusal to participate of those candidate subjects (21,22). A local study established that 64% of patients would be willing to participate in a CT and that the most determinant factors in the decision are related to the information received about the risks and benefits, participation rights and informed, independent consent. Other factors such as sociocultural factors and education level (23) in this study accepted to participate in clinical trials was 45.5%. Many patients when asked to participate in clinical trials express high expectations and concerns that include, among others, the fear of presenting a reduction in their quality of life, the concern about receiving a placebo, the potential side effects, the concern that the drug in research may not be the best option, strictness of participation, aversion to randomization, feeling coerced, and loss of control over your treatment decisions (24–26).

The evidence supporting the belief that participation in clinical trials produces better clinical outcomes is insufficient (7), In this sense, the evidence that contributes to knowledge and allows adequately determining the impact of patient participation in clinical trials acquires high relevance. in cancer on clinical outcomes. Some published studies in this regard lack adequate comparability between participants and non-participants in a clinical trial, which is a fundamental factor that may call into question the generalization of the results because they include in their analyzes outcomes of regular care patients and patients enrolled in clinical studies (27).

In this research we sought to establish a better comparison between the groups, because from those patients who were eligible to participate in a clinical study, a comparison of clinical outcomes was made between those who agreed to participate and those who refused. We found subtle differences in the variables of social security, socioeconomic status, and clinical stage. Regarding clinical outcomes, a higher occurrence of non-serious adverse events was observed in the group of participants (HR 11.0 (4.3 - 28.4), p= 0.000), however, this could be explained at least in part by the greater rigor in the recording of any adverse event during a clinical study than in real life clinical practice. It was also observed that the refuser group presented 28% more disease progression than the participants and mortality was 20% higher in the group of rejecters, similar to what was reported by Chow et al. to where participants in clinical trials had a lower risk of death (28). Therefore, it can be considered that participation in clinical trials could give participants a better response to treatment, without increasing the probability of death and with the probability of decreasing the progression of the disease. participation in trials could improve the outcomes of clinical response rates, no change in overall survival, and progression-free.

Studies that have compared survival between participants have shown mixed results, while the Toxopeus study reported a median survival of 58.5 months (IQR 19.0-86.8) in the non-participant group vs 35.0 (IQR 12.9-51.4). in the participant group (95% CI 16.1-29.4) (11); in contrast to the study by Davis et al, it was reported that participation in a clinical trial was associated with better survival at 12 and 24 months 93% and 82% vs 72% and 50% in non-participants (29). In this study we observed that the percentage of patients alive at 12 months was 10.9% higher in the group of participants vs. refusers, just as the proportion of patients without progression at 12 months was also 27.1% higher among the participants; however, this result was not consistent over time, noting that both mean progression-free survival and overall survival were numerically lower for participants did not show statistical significance.

It continues to be complex to adequately establish survival patterns among participants in clinical trials; Factors such as age, the presence of comorbidities, the type of cancer, histology, clinical stage, functional status, type of treatment, among others, influence survival, especially in the first year, for which the rigor of the screening criteria Eligibility to enter a clinical trial that usually excludes patients with higher comorbidities could explain these differences. (8). Corresponding to the above, in this research we observed that the functional status determined by the ECOG was a significant predictor of survival HR 0.48 (CI95% 0.23–0.97) p = 0.042.

In summary, the results of this research should be taken with caution, considering the limitations of the design, the size of the sample, and the types of tumors that were included; however, these results may contribute to partially reduce the existing uncertainty about the effect of participation in clinical trials on some of the outcomes of cancer patients. Complementary studies are also required to help reduce the gap between the expectations of patients and the effect of participation on health status.

Ethics approval and consent to participate

Name: ethic and research committee at the National Cancer Institute

Date approval: june/ 26/ 2019

N° 0017-19.

Level Of risk: without risk – observational study

This research complied with the guidelines established by the Declaration of Helsinki and the ethical guidelines for biomedical research prepared by the Council for International Organizations of Medical Sciences (CIOMS) and with the parameters established by national regulations, additionally it was approved by the ethic and research committee at the National Cancer Institute of Colombia.

The requirement of informed consent was waived by the ethic and research committee at the National Cancer Institute of Colombia as it considered this investigation without risk (observational study) and the results did not contain any data of identification for patients."

Consent for publication

Not required

Availability of data and materials

Data is available in RedCap, but restrictions apply to the availability of these data

https://redcap.cancer.gov.co/redcap_v7.1.2/DataExport/index.php?pid=270

Please contact the Corresponding author if someone wants to request the data from this study ([email protected], [email protected])

Competing interests

Not applicable

Funding

Not applicable

Authors' contributions

Carreno J: principal author, idea concept and design study

Sanchez N: Data análisis

Bonilla C: discusión, idea and concept

Acknowledgements

Cancer patients at the National cancer Institute

Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidence based medicine: what it is and what it isn’t. Vol. 312, BMJ (Clinical research ed.). England; 1996. p. 71–2.
Institute NC. Cancer Clinical Trials [Internet]. 2022. Available from: http://www.cancer.gov/cancertopics/factsheet/Information/clinical-trials
Hwang TJ, Gyawali B. Association between progression-free survival and patients’ quality of life in cancer clinical trials. Int J cancer. 2019 Apr;144(7):1746–51.
Commissioning support for London. A model of care for cancer services Clinical paper. London; 2010.
Fiteni F, Westeel V, Pivot X, Borg C, Vernerey D, Bonnetain F. Endpoints in cancer clinical trials. J Visc Surg. 2014 Feb;151(1):17–22.
Engelbak Nielsen Z, Eriksson S, Schram Harsløf LB, Petri S, Helgesson G, Mangset M, et al. Are cancer patients better off if they participate in clinical trials? A mixed methods study. BMC Cancer [Internet]. 2020;20(1):401.
Peppercorn JM, Weeks JC, Cook EF, Joffe S. Comparison of outcomes in cancer patients treated within and outside clinical trials: conceptual framework and structured review. Lancet (London, England). 2004 Jan;363(9405):263–70.
Unger JM, Barlow WE, Martin DP, Ramsey SD, Leblanc M, Etzioni R, et al. Comparison of survival outcomes among cancer patients treated in and out of clinical trials. J Natl Cancer Inst. 2014 Mar;106(3):dju002.
Braunholtz DA, Edwards SJ, Lilford RJ. Are randomized clinical trials good for us (in the short term)? Evidence for a “trial effect”. J Clin Epidemiol. 2001 Mar;54(3):217–24.
Sedgwick P, Greenwood N. Understanding the Hawthorne effect. BMJ Br Med J [Internet]. 2015 Sep 4;351:h4672.
Toxopeus E, van der Schaaf M, van Lanschot J, Lagergren J, Lagergren P, van der Gaast A, et al. Outcome of Patients Treated Within and Outside a Randomized Clinical Trial on Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: Extrapolation of a Randomized Clinical Trial (CROSS). Ann Surg Oncol. 2018 Aug;25(8):2441–8.
Chow S-C. Design and Analysis of Clinical Trials, Concepts and Methodologies. Second Edi. Library of Congress Cataloging-in-Publication Data is available., editor. New Jersey: John Wiley & Sons, Inc., Hoboken, New Jersey; 2004. 750 p.
Booth CM, Tannock I. Reflections on medical oncology: 25 years of clinical trials--where have we come and where are we going? J Clin Oncol. 2008 Jan;26(1):6–8.
Rosselli D, Eduardo C, Gutiérrez L. Desenlaces clínicos en hematoncología : diez años de investigaciones en Pubmed. Rev Colomb Cancerol. 2015;19(2):19–26.
Wilson MK, Karakasis K, Oza AM. Outcomes and endpoints in trials of cancer treatment: the past, present, and future. Lancet Oncol. 2015 Jan;16(1):e32–42.
McDonald AM, Knight RC, Campbell MK, Entwistle VA, Grant AM, Cook JA, et al. What influences recruitment to randomised controlled trials? A review of trials funded by two UK funding agencies. Trials [Internet]. 2006;7(1):9.
Nipp RD, Hong K, Paskett ED. Overcoming Barriers to Clinical Trial Enrollment. Am Soc Clin Oncol Educ B [Internet]. 2019 May 1;(39):105–14.
Institute of Medicine (US) Forum on Drug Discovery Development and Translation. Transforming Clinical Research in the United States: Challenges and Opportunities: Workshop Summary. Washington (DC): Washington (DC): National Academies Press (US); 2010. PMID: 21210556.; 2010.
Murthy VH, Krumholz HM, Gross CP. Participation in cancer clinical trials: race-, sex-, and age-based disparities. JAMA. 2004 Jun;291(22):2720–6.
Unger JM, Vaidya R, Hershman DL, Minasian LM, Fleury ME. Systematic Review and Meta-Analysis of the Magnitude of Structural, Clinical, and Physician and Patient Barriers to Cancer Clinical Trial Participation. J Natl Cancer Inst. 2019 Mar;111(3):245–55.
Claessens MT, Bernat JL, Baron JA. Ethical issues in clinical trials. Br J Urol. 1995 Nov;76 Suppl 2:29–36.
Jenkins V, Farewell D, Batt L, Maughan T, Branston L, Langridge C, et al. The attitudes of 1066 patients with cancer towards participation in randomised clinical trials. Br J Cancer [Internet]. 2010 Dec 7 [cited 2013 Jan 31];103(12):1801–7.
Carreño D. Alexander. Factores asociados con la participación de pacientes en ensayos clínicos en cáncer. Rev Colomb Cancerol. 2017;21(3):136–42.
Moorcraft SY, Marriott C, Peckitt C, Cunningham D, Chau I, Starling N, et al. Patients’ willingness to participate in clinical trials and their views on aspects of cancer research: results of a prospective patient survey. Trials. 2016 Jan;17:17.
Weinfurt KP, Seils DM, Lin L, Sulmasy DP, Astrow AB, Hurwitz HI, et al. Research participants’ high expectations of benefit in early-phase oncology trials: are we asking the right question? J Clin Oncol Off J Am Soc Clin Oncol. 2012 Dec;30(35):4396–400.
Chu SH, Jeong SH, Kim EJ, Park MS, Park K, Nam M, et al. The views of patients and healthy volunteers on participation in clinical trials: an exploratory survey study. Contemp Clin Trials [Internet]. 2012 Jul [cited 2013 Apr 16];33(4):611–9.
Elting LS, Cooksley C, Bekele BN, Frumovitz M, Avritscher EBC, Sun C, et al. Generalizability of cancer clinical trial results: prognostic differences between participants and nonparticipants. Cancer. 2006 Jun;106(11):2452–8.
Chow CJ, Habermann EB, Abraham A, Zhu Y, Vickers SM, Rothenberger DA, et al. Does enrollment in cancer trials improve survival? J Am Coll Surg. 2013 Apr;216(4):771–4.
Davis S, Wright PW, Schulman SF, Hill LD, Pinkham RD, Johnson LP, et al. Participants in prospective, randomized clinical trials for resected non-small cell lung cancer have improved survival compared with nonparticipants in such trials. Cancer. 1985 Oct;56(7):1710–8.

Table 1. Patient and tumor characteristics of 112 patients, divided into the clinical trials participant

		Clinical Trials Participant
		Yes	No	Total	p values
Age	>65	24	28	52	0,9
Age	<65	27	33	60	0,9
Sex	Women	31	31	62	0,29
Sex	Men	20	30	50	0,29
Location	Rural	6	6	12	0,74
Location	Urban	45	55	100	0,74
Social Security	Contribute	42	27	69	0,000
Social Security	Subsidiado	9	34	43	0,000
Poverty Level	1	5	13	18	0,006
	2	11	8	19
	3	28	40	68
	4	7	0	7
Education Level	None	0	1	1	0,04
	Primary School	23	23	46
	High School	22	35	57
	Technician	3	0	3
	University	3	0	3
	Postgraduate	0	2	2
Tumor	Cervix	31	31	62	0,29
Tumor	Prostate	20	30	50	0,29
ECOG	0	14	26	40	0,08
	1	36	31	67
	2	1	4	5
Clinical Stage	I	0	8	8	0,000
	II	0	8	8
	IIIA	2	9	11
	IIIB	22	15	37
	IV (IVA – IVB)	27	21	48
Clinical T stage	cT0	9	17	26	0,25
	cT1	9	14	23
	cT2	3	5	8
	cT3	15	6	21
	cT4	11	13	24
	cTx	3	5	8
Clinical N stage	cN0	20	26	46	0,3
	cN1	16	10	26
	cN2	1	0	1
	cN3	0	1	1
	cNx	13	22	35
	ND	1	2	3
Metastastic disease	M0	32	44	76	0,47
	M1	17	14	31
	ND	2	3	5

Table 2. Hazard ratios for Clinical Outcomes, comparing clinical trials participant

		Clinical Trials Participant
Outcomes		Yes	No	Total	HR IC-95%	p values
Event adverse	Yes	45	4	49	11,0 (4,3-28,4)	0.000
Event adverse	No	6	57	63	11,0 (4,3-28,4)	0.000
Overall Response	PD	16	35	51		0.000
	SD	16	26	42
	CR	14	0	14
	PR	5	0	5
Disease Free	Yes	2	0	2	0,4 (0,3-0,5)	0.119
Disease Free	No	49	61	110	0,4 (0,3-0,5)	0.119
Progression	Yes	14	25	39	0,5 (0,2-1,1)	0.134
Progression	No	37	36	73	0,5 (0,2-1,1)	0.134
Death	Yes	12	18	30	0,73 (0,3-1,7)	0.477
Death	No	39	43	82	0,73 (0,3-1,7)	0.477

Overall Response: Complete Response (CR) – Partial Response (PR) – Stable Disease (SD) – Progression Disease (PD)

Table 3. Univariate Cox regression analysis for overall survival

	HRs (95% CI)	p values
Age (continuous)	0,98 (0,97-1,0)	0,23
Age (<65y vs >65y)	1,16 (0,80-1,68)	0,41
Sex (men vs women)	0,74 (0,51-1,07)	0,117
Cancer type (cervix vs prostate)	1,34 (0,92-1,95)	0,117
Clinical stage
I	0,46 (0,08-2,61)	0,38
II	0,48 (0,09-2,60)	0,4
IIIA-IIIB	0,83 (0,22-3,1)	0,79
IVA-IVB	1,65 (0,54-5,04)	0,37
ECOG
0	-	0,12
1	0,48 (0,23-0,97)	0,04
2	1,01 (0,55-1,8)	0,95
Metastastic disease
M0	0,84 (0,39-1,82)	0,67
M1	1,48 (0,68-3,22)	0,31
Participants (yes vs no)	1,09 (0,74-1,6)	0,64

No competing interests reported.

Comparison of clinical outcomes among cancer patients treated in and out of clinical trials

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Abstract

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