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Improving bladder cancer outcomes: The impact of initiating a phase IV randomised controlled clinical trial
British Journal of Medical and Surgical Urology (2009) 2, 67—72
ORIGINAL ARTICLE
Improving bladder cancer outcomes: The impact of initiating a phase IV randomised controlled clinical trial Eleanor R. Ray ∗, Bola Coker, Kathryn Chatterton, Mohamed S. Khan, Tim S. O’Brien The Urology Centre, Guy’s Hospital, St. Thomas’ Street, London SE1 9RT, UK Received 26 October 2008; accepted 9 November 2008
KEYWORDS Quality of care; Bladder cancer; Clinical trial
Summary Objective: The aim of this study was to determine if patients newly diagnosed with bladder cancer and included in a clinical trial had better outcomes than similar patients treated in the same department before initiation of the trial. Methods: Forty patients presenting with bladder cancer in 2005 and recruited into a randomised trial of photodynamic-assisted tumour resection were compared with a cohort of 40 non-trial patients from 2004. Quality of care was measured by assessing near-miss criteria. Results: There were fewer near-misses in the Trial Group (TG) than in the Control Group (CG) (52 versus 151) (p < 0.001). There were 15 surgical near-misses in the TG compared with 90 in the CG (p = 0.025). Adjuvant intravesical chemotherapy was given within 6 h of resection in 26/31(84%) of the TG and 1/23(4%) of the CG. There were 37 process near-misses in the TG compared with 61 in the CG (p = 0.002). The times to first outpatient appointment, diagnostic flexible cystoscopy, and outpatient follow-up were shorter in the TG (median 10.5/25/17.5 days) than the CG (median 17/32.5/26 days). Conclusions: Patients in the trial had better outcomes than non-trial patients the previous year. The recruitment of patients into trials is a valuable driver of quality improvement. © 2008 British Association of Urological Surgeons. Published by Elsevier Ltd. All rights reserved.
∗ Corresponding author at: Freeman Hospital, High Heaton, Newcastle upon Tyne, NE7 7DN United Kingdom. Tel.: +44 7747 534417;fax: +44 191 3332310. E-mail addresses: [email protected] (E.R. Ray), [email protected] (B. Coker), [email protected] (K. Chatterton), [email protected] (M.S. Khan), [email protected] (T.S. O’Brien).
1875-9742/$ — see front matter © 2008 British Association of Urological Surgeons. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.bjmsu.2008.11.006
68
Introduction Patients may choose to enter into a clinical trial for a number of reasons. Usually they believe that novel treatments or the most recent technological advances are superior to standard care, and that they are therefore likely to benefit if they are exposed to them. The perception of personal benefit was the factor most significantly correlated with a decision to enter a trial in one study, but still 39% of these patients perceived that there may be serious side effects from a new treatment [1]. Recruitment of patients into clinical trials can be problematic, perhaps because of the perception of risk fuelled by occasional extensive media coverage of sporadic catastrophes in individual trials. A Cochrane review has found that the outcomes of patients participating in trials are similar to those that do not participate and concluded from this that any risks of participating in trials are low [2]. Only 11% of the comparisons however found a direct benefit for patients in trials when outcomes such as pain and function were analysed. Participation in a clinical trial may though have ‘indirect benefits’ which derive from the well-organised care processes that characterise research. One way to measure these indirect benefits would be to attempt to measure the quality of care delivered to the patients in the trial. Quality of healthcare has six domains each of which can be potentially measured; viz, safety, effectiveness, timeliness, efficiency, patient-centred and equity. The National Patient Safety Agency uses ‘near misses’ or ‘prevented patient safety incidents’ as a tool to assess the quality of care [3]. We have used near miss criteria to test the hypothesis that recruitment into our trial of photodynamic diagnosis (PDD) led to better outcomes for patients newly diagnosed with bladder cancer at Guy’s Hospital.
Patients and methods The quality of care of patients newly diagnosed with bladder cancer was measured by the number of near misses they encountered during diagnosis, admission for transurethral resection of bladder tumour (TURBT) and initial follow-up. The number of near misses occurring in the first 40 patients in the PDD bladder cancer trial at Guy’s Hospital was then compared with those occurring in 40 patients newly diagnosed with bladder cancer and managed in the same department before initiation of the trial protocol. Data collection was prospective from
E.R. Ray et al. patients recruited into the trial between March 2005 and December 2005 (Trial Group (TG)) [4] and was retrospective from the cohort of patients undergoing TURBT between March and September 2004 who retrospectively fulfilled trial eligibility (Control Group (CG)). The PDD trial is a randomised controlled study of standard ‘white light’ TURBT compared to photodynamic assisted ‘white light + blue light’ TURBT. Inclusion criteria for the PDD trial were: a new diagnosis of bladder tumour on cystoscopy or imaging; suspected non-muscle invasive bladder cancer (NMIBC); no history of previous bladder surgery; no concurrent or previous upper tract TCC; and life expectancy of at least one year. Exclusion criteria included porphyria; pregnancy or breastfeeding; suspected allergy to intravesical photosensitizers; urinary tract infection; and suspected muscle invasive disease, e.g. hydronephrosis. Data were obtained from a combination of case report forms (CRF), review of patient case notes, from letters stored electronically and from the hospital electronic patient record (EPR) database. Data were collected on patient characteristics to check the equivalence of cohorts. Near miss criteria were based on previously published work [5] and EAU guidelines for NMIBC [6]. The criteria were divided into two categories (i) ‘process’ nearmisses which include administrative and capacity related events (Table 1a) and (ii) ‘surgery’ nearmisses which include surgical and pathology related events (Table 1b). If minimum standards were not reached for each criteria for each patient, it was labelled a near miss.
Table 1a
‘Process’ near miss criteria.
Diagnostic flexible cystoscopy >4 week since referral for macroscopic haematuria >12 week since referral for microscopic haematuria >2 week since urgent GP referral 2 week wait Admission to hospital prior to TURBT >8 week since symptoms if a new patient >3 week for stage T1, Carcinoma-in situ (CIS) or Grade 3 tumours Absent or unavailable upper tract imaging or medical notes No pre-assessment Admission after 16:00 Cancelled procedure due to bed shortage or patient non-attendance First outpatient consultation >4 week since surgery Absent or incomplete imaging (if not present at operation)
Improving bladder cancer outcomes Table 1b
69 32.5, respectively). The majority of near misses were in patients with macroscopic haematuria: all 18 near misses in the CG and 11/12 (92%) near misses in the TG. In patients with microscopic haematuria only 1/3 (33%) in the TG and 0/5 in the CG had flexible cystoscopy more than 12 weeks after referral.
‘Surgery’ near miss criteria.
Pre-operative urine cytology absent Pre-operative urinalysis absent No evidence of or failure to administer intravesical Mitomycin-C within 6 h of surgery Absence of documented examination under anaesthetic Absence of histology report at 1st outpatients appointment Absence of muscle in specimen Incorrect TNM classification on final summary report No evidence of discussion at multidisciplinary team meeting
Time from diagnosis to TURBT There was no difference between the two groups for median time from diagnosis to TURBT (CG 9 days, TG 10 days), and there were a similar number of near misses (3 versus 2) in each group.
The two-tail two-sample Student’s t-test was used to compare cohorts for age and co-morbidity. The two-tail Fisher’s exact test (FET) was used to check expected proportions for referral and presentation. To test proportions and durations for process and surgical criteria the two-tailed FET and two-tail two-sample Student’s t-test were used.
Results The clinical features of the two cohorts are summarized in Table 2. The two groups are comparable. Case notes were unavailable for two patients. The total number of near misses in the TG was 52 compared with a total number of 151 in the CG. This is statistically significant (p < 0.001).
Process criteria For process criteria alone there were 37 near misses in the TG and 61 near misses in the CG (p = 0.002) (Table 3). Diagnosis The time to first outpatient appointment and time to diagnostic flexible cystoscopy were shorter in the TG (median number of days 10.5 and 25, respectively) than the CG (median number of days 17 and
Table 2
Follow-up All patients were followed up in clinic following surgery. All trial patients were reviewed within 30 days following TURBT, whereas in the CG follow-up was often delayed. In the CG three patients were seen more than 100 days after surgery.
Surgical criteria There were 15 surgery related near misses in the TG compared with 90 near misses in the CG (p = 0.001) (Table 4). In the TG initial management and TURBT were by seven surgeons who worked in two teams whilst in the CG it was by 14 surgeons in six teams. In the TG more TURBTs were carried out by very experienced surgeons: 17/40 (43%) were done by two consultants and no TURBT was carried out by research fellows. In comparison in the CG 10/40 (25%) TURBTs were done by consultants and 6/40 (15%) TURBTs were done by two research fellows. Similar numbers of TURBTs were performed by specialist registrars in both groups 22/40 (55%). Adjuvant chemotherapy There were 35 near misses in the CG and none in the TG relating to the administration of perioperative intravesical chemotherapy. Adjuvant single shot intravesical chemotherapy was given within 6 h of completion of TURBT in 26/31 (84%) of patients in the TG and 1/23 (4%) of patients in the CG (Table 4).
Patients and presentation. Control Group
Trial Group
Age (median:range) Charlson age-comorbidity score
71 (36—92) 3 (0—11)
72.5 (39—94) 3 (0—6) median (range)
Referral details Urgent referral
26/32 (81%)
22/32 (69%)
Presentation Macrohaematuria
26/33 (79%)
36/40 (90%)
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E.R. Ray et al.
Table 3
‘Process’ criteria near misses.
Near misses
Control Group
Trial Group
5/40 (13%) 7/40 (18%) 28/40 (70%) Median 32.5 days Range (0—286) 18
1/40 (3%) 5/40 (13%) 34/40 (85%) Median 25 days Range (5—91) 12
Time from diagnosis to TURBT
Median 9 days Range (1—85)
Median 10 days Range (1—254)
Near misses
3
2
Time from TURBT to results OPA
Median 26 days Range (13—126)
Median 17.5 days Range (6—30)
Near misses
10
3
p = 0.067 p = 0.033a
Absent or unavailable upper tract imaging or medical notes No pre-assessment
4 26/38 (68%)
2 18/40 (45%)
p = 0.675 p = 0.115
Total
61
37
p = 0.003a
Time from referral to flexible cystoscopy Not known No flexi. cystoscopy Flexi. cystoscopy done
Near misses
a
p = 0.119 p = 0.069
p = 1.000 p = 0.500
Statistically significant.
Table 4
‘Surgical’ criteria near misses.
Near misses
Control Group
Trial Group
Pre-op cytology absent Pre-operative urinalysis absent
11/40 (28%) 9/40 (23%)
3/40 (8%) 2/40 (5%)
p = 0.037a p = 0.024a
Administration of adjuvant chemotherapy No relating documentation Not given, reason not documented Given Day of TURBT (>6 h) Day 1 Total
7/38 (18%) 6/38 (16%)b 23/38 (61%)c 4/23 (17%) 18/23 (78%) 35
0/40 0/40d 31/40 (78%) 0 0 0
p < 0.001a
Absence of examination under anaesthetic (EUA) (only 33 operation notes available) Absence of histology report at 1st OPA Absence of muscle in specimen Not discussed at MDM
7/33 (21%)
3/40 (8%)
p = 0.177
1/40 (2.5%) 9/40 (23%) 18/38 (47%)
0 7/40 (18%) 0/40
p = 1.000 p = 0.781 p < 0.001a
Total
90
15
p = 0.001a
a b c d
Statistically significant. In 2 cases chemotherapy was not given but the reason was documented. In 1 case chemotherapy was given within 6 h. In 9 cases chemotherapy was not given but the reason was documented.
In the CG adjuvant chemotherapy was mostly given the day following surgery (n = 18/23 (78%)). Pathology The proportion of pathology specimens not containing detrusor muscle was similar in the two groups. For two patients in the TG the histological diagnosis was changed at the MDM: one was upgraded from G2pTa to focal CIS and one was downgraded from G2pTa with focal CIS to papillary neoplasm
of low malignant potential. Interestingly, in the CG there was no documentation of discussion at MDM for 18/32 (56%) of patients and these were counted as near misses.
Discussion This study has shown that the initiation of a clinical trial in our hospital has markedly improved the
Improving bladder cancer outcomes quality of care delivered to patients in the trial. There were statistically significant improvements in both process and surgical criteria. This study is different to previous studies on the topic. A recent Cochrane review [2] assessed studies which measured direct outcomes related to the treatment received rather than quality of care which may be considered an indirect benefit. The improvements in surgical factors may relate to the Hawthorne effect. Elton Mayo’s interpretation of research in industry was that workers who were being closely observed improved their performance: the important effect was the feeling of being studied [7,8]. In the present study the Hawthorne effect may operate at various interfaces: nurses may be performing better by ensuring that urine is collected; patients may be performing better by being more likely to keep their appointments; surgeons may be carrying out more careful TURBT. In essence, the Hawthorne effect could lead to fewer near misses due to improvements in both clinician and patient performance. Alternatively, the existence of an explicit trial protocol stating, for example, that post-operative mitomycin C should be given within 6 h of TURBT, may be the reason for better performance. In 2004 patients newly diagnosed with bladder cancer were managed by any one of six teams at Guy’s Hospital. In 2005 the initiation of the PDD trial led to the reorganisation of bladder cancer care in the department. The trial protocol stipulated that all eligible patients be under the care of one of two consultants: this arrangement was felt to be more practical and was the best way of ensuring that the surgeons were all highly skilled at PDDassisted TURBT. This reorganisation itself may have led to a reduction in near misses and better quality of care, although it would have been interesting to know what the near misses were for the two bladder cancer teams alone, compared to the six overall, before the trial in 2004, as this may have introduced a bias. The trial has not led to more rapid admission to hospital for TURBT after diagnosis. Standards were excellent in 2004 and remain so. More patients in the TG had their operation performed by a consultant urologist (43% versus 25%) however, and no trial patients had surgery by a research registrar. This is an important change because it has been suggested that the observed variability in recurrence rates in NMIBC is related to the quality of TURBT and therefore the experience of the surgeon [9]. Administrative errors have undoubtedly been reduced because the supervision of trial patients has been in the hands of one researcher. Delays in
71 care post-TURBT have been improved. All patients in the trial were seen in clinic with histology results by 30 days following surgery. In the CG one patient had no report to discuss by the time of follow-up (documented in the clinic letter) and three patients were seen more than 100 days after surgery with no documentation of a reason why. The difference in time from TURBT to results OPA was statistically significant (p = 0.033), but it is possible that prospective data collection for the trial patients and retrospective data collection for the control patients has introduced a mode effect. Not all the improvements identified in this study relate to the organisation of the trial. Patients are referred for consideration for trial entry after the diagnosis of a new bladder cancer. Improvements in time to referral are therefore outside the remit of the trial. Additionally, there are likely to be other benefits for patients in the trial that cannot be measured by near miss criteria. A patient satisfaction questionnaire would have been be a good adjunct to this near miss study but would only have been valid if taken prospectively for both groups.
Conclusion The initiation of a bladder cancer trial at Guy’s hospital, which led to a reorganisation of the management of bladder cancer, has manifestly improved the standard of care for all patients in the trial. The indirect benefits of being in a trial need to be more strongly communicated to patients. These benefits could potentially be made available to patients outside a trial setting by using a treatment protocol; limiting the number of surgeons; and increasing the seniority of surgeons. Rigorous audit may even produce a Hawthorne effect in the non-research setting. The recruitment of patients into trials is potentially a valuable driver of quality improvement.
Conflict of interest The authors declare that there are no conflicts of interest.
Acknowledgement We thank all the urologists who have referred patients into this study.
72
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References [1] Wright J, Whelan TJ, Schiff S, Dubois S, Crooks D, Haines PT, et al. Why cancer patients enter randomized clinical trials: exploring the factors that influence their decision. J Clin Oncol 2004;22:4312—8. [2] Vist GE, Hagen KB, Devereaux PJ, Bryant D, Oxman AD. Outcomes of patients who participate in randomised controlled trials compared to similar patients receiving similar interventions who do not participate. Cochrane Database Syst Rev 2007. [3] National patient safety agency: doing less harm. Department of Health. [4] ISRCTN 14275387. 2-9-2005. Ref Type: Internet Communication.
[5] Singh R, Saleemi A, Walsh K, Popert R, O’Brien T. Near misses in bladder cancer—–an airline safety approach to urology. Ann R Coll Surg Engl 2003;85:378—81. [6] Babjuk M, Oosterlinck W, Sylvester R, Kaasinen E, Bohle A, Palou J. EAU: Guidelines on T1Ta (non-muscle invasive) bladder cancer, Chapter 1; 2008 edition. [7] Hsueh Y. The Hawthorne experiments and the introduction of Jean Piaget in American industrial psychology, 1929—1932. Hist Psychol 2002;5:163—89. [8] Mayo E. The human problems of an industrial civilization. New York: MacMillan; 1933. Chapter 3. [9] Brausi M, Collette L, Kurth K, van der Meijden AP, Oosterlinck W, Witjes JA, et al. Variability in the recurrence rate at first follow-up cystoscopy after TUR in stage Ta T1 transitional cell carcinoma of the bladder: a combined analysis of seven EORTC studies. Eur Urol 2002;41:523—31.
Available online at www.sciencedirect.com
ORIGINAL ARTICLE
Improving bladder cancer outcomes: The impact of initiating a phase IV randomised controlled clinical trial Eleanor R. Ray ∗, Bola Coker, Kathryn Chatterton, Mohamed S. Khan, Tim S. O’Brien The Urology Centre, Guy’s Hospital, St. Thomas’ Street, London SE1 9RT, UK Received 26 October 2008; accepted 9 November 2008
KEYWORDS Quality of care; Bladder cancer; Clinical trial
Summary Objective: The aim of this study was to determine if patients newly diagnosed with bladder cancer and included in a clinical trial had better outcomes than similar patients treated in the same department before initiation of the trial. Methods: Forty patients presenting with bladder cancer in 2005 and recruited into a randomised trial of photodynamic-assisted tumour resection were compared with a cohort of 40 non-trial patients from 2004. Quality of care was measured by assessing near-miss criteria. Results: There were fewer near-misses in the Trial Group (TG) than in the Control Group (CG) (52 versus 151) (p < 0.001). There were 15 surgical near-misses in the TG compared with 90 in the CG (p = 0.025). Adjuvant intravesical chemotherapy was given within 6 h of resection in 26/31(84%) of the TG and 1/23(4%) of the CG. There were 37 process near-misses in the TG compared with 61 in the CG (p = 0.002). The times to first outpatient appointment, diagnostic flexible cystoscopy, and outpatient follow-up were shorter in the TG (median 10.5/25/17.5 days) than the CG (median 17/32.5/26 days). Conclusions: Patients in the trial had better outcomes than non-trial patients the previous year. The recruitment of patients into trials is a valuable driver of quality improvement. © 2008 British Association of Urological Surgeons. Published by Elsevier Ltd. All rights reserved.
∗ Corresponding author at: Freeman Hospital, High Heaton, Newcastle upon Tyne, NE7 7DN United Kingdom. Tel.: +44 7747 534417;fax: +44 191 3332310. E-mail addresses: [email protected] (E.R. Ray), [email protected] (B. Coker), [email protected] (K. Chatterton), [email protected] (M.S. Khan), [email protected] (T.S. O’Brien).
1875-9742/$ — see front matter © 2008 British Association of Urological Surgeons. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.bjmsu.2008.11.006
68
Introduction Patients may choose to enter into a clinical trial for a number of reasons. Usually they believe that novel treatments or the most recent technological advances are superior to standard care, and that they are therefore likely to benefit if they are exposed to them. The perception of personal benefit was the factor most significantly correlated with a decision to enter a trial in one study, but still 39% of these patients perceived that there may be serious side effects from a new treatment [1]. Recruitment of patients into clinical trials can be problematic, perhaps because of the perception of risk fuelled by occasional extensive media coverage of sporadic catastrophes in individual trials. A Cochrane review has found that the outcomes of patients participating in trials are similar to those that do not participate and concluded from this that any risks of participating in trials are low [2]. Only 11% of the comparisons however found a direct benefit for patients in trials when outcomes such as pain and function were analysed. Participation in a clinical trial may though have ‘indirect benefits’ which derive from the well-organised care processes that characterise research. One way to measure these indirect benefits would be to attempt to measure the quality of care delivered to the patients in the trial. Quality of healthcare has six domains each of which can be potentially measured; viz, safety, effectiveness, timeliness, efficiency, patient-centred and equity. The National Patient Safety Agency uses ‘near misses’ or ‘prevented patient safety incidents’ as a tool to assess the quality of care [3]. We have used near miss criteria to test the hypothesis that recruitment into our trial of photodynamic diagnosis (PDD) led to better outcomes for patients newly diagnosed with bladder cancer at Guy’s Hospital.
Patients and methods The quality of care of patients newly diagnosed with bladder cancer was measured by the number of near misses they encountered during diagnosis, admission for transurethral resection of bladder tumour (TURBT) and initial follow-up. The number of near misses occurring in the first 40 patients in the PDD bladder cancer trial at Guy’s Hospital was then compared with those occurring in 40 patients newly diagnosed with bladder cancer and managed in the same department before initiation of the trial protocol. Data collection was prospective from
E.R. Ray et al. patients recruited into the trial between March 2005 and December 2005 (Trial Group (TG)) [4] and was retrospective from the cohort of patients undergoing TURBT between March and September 2004 who retrospectively fulfilled trial eligibility (Control Group (CG)). The PDD trial is a randomised controlled study of standard ‘white light’ TURBT compared to photodynamic assisted ‘white light + blue light’ TURBT. Inclusion criteria for the PDD trial were: a new diagnosis of bladder tumour on cystoscopy or imaging; suspected non-muscle invasive bladder cancer (NMIBC); no history of previous bladder surgery; no concurrent or previous upper tract TCC; and life expectancy of at least one year. Exclusion criteria included porphyria; pregnancy or breastfeeding; suspected allergy to intravesical photosensitizers; urinary tract infection; and suspected muscle invasive disease, e.g. hydronephrosis. Data were obtained from a combination of case report forms (CRF), review of patient case notes, from letters stored electronically and from the hospital electronic patient record (EPR) database. Data were collected on patient characteristics to check the equivalence of cohorts. Near miss criteria were based on previously published work [5] and EAU guidelines for NMIBC [6]. The criteria were divided into two categories (i) ‘process’ nearmisses which include administrative and capacity related events (Table 1a) and (ii) ‘surgery’ nearmisses which include surgical and pathology related events (Table 1b). If minimum standards were not reached for each criteria for each patient, it was labelled a near miss.
Table 1a
‘Process’ near miss criteria.
Diagnostic flexible cystoscopy >4 week since referral for macroscopic haematuria >12 week since referral for microscopic haematuria >2 week since urgent GP referral 2 week wait Admission to hospital prior to TURBT >8 week since symptoms if a new patient >3 week for stage T1, Carcinoma-in situ (CIS) or Grade 3 tumours Absent or unavailable upper tract imaging or medical notes No pre-assessment Admission after 16:00 Cancelled procedure due to bed shortage or patient non-attendance First outpatient consultation >4 week since surgery Absent or incomplete imaging (if not present at operation)
Improving bladder cancer outcomes Table 1b
69 32.5, respectively). The majority of near misses were in patients with macroscopic haematuria: all 18 near misses in the CG and 11/12 (92%) near misses in the TG. In patients with microscopic haematuria only 1/3 (33%) in the TG and 0/5 in the CG had flexible cystoscopy more than 12 weeks after referral.
‘Surgery’ near miss criteria.
Pre-operative urine cytology absent Pre-operative urinalysis absent No evidence of or failure to administer intravesical Mitomycin-C within 6 h of surgery Absence of documented examination under anaesthetic Absence of histology report at 1st outpatients appointment Absence of muscle in specimen Incorrect TNM classification on final summary report No evidence of discussion at multidisciplinary team meeting
Time from diagnosis to TURBT There was no difference between the two groups for median time from diagnosis to TURBT (CG 9 days, TG 10 days), and there were a similar number of near misses (3 versus 2) in each group.
The two-tail two-sample Student’s t-test was used to compare cohorts for age and co-morbidity. The two-tail Fisher’s exact test (FET) was used to check expected proportions for referral and presentation. To test proportions and durations for process and surgical criteria the two-tailed FET and two-tail two-sample Student’s t-test were used.
Results The clinical features of the two cohorts are summarized in Table 2. The two groups are comparable. Case notes were unavailable for two patients. The total number of near misses in the TG was 52 compared with a total number of 151 in the CG. This is statistically significant (p < 0.001).
Process criteria For process criteria alone there were 37 near misses in the TG and 61 near misses in the CG (p = 0.002) (Table 3). Diagnosis The time to first outpatient appointment and time to diagnostic flexible cystoscopy were shorter in the TG (median number of days 10.5 and 25, respectively) than the CG (median number of days 17 and
Table 2
Follow-up All patients were followed up in clinic following surgery. All trial patients were reviewed within 30 days following TURBT, whereas in the CG follow-up was often delayed. In the CG three patients were seen more than 100 days after surgery.
Surgical criteria There were 15 surgery related near misses in the TG compared with 90 near misses in the CG (p = 0.001) (Table 4). In the TG initial management and TURBT were by seven surgeons who worked in two teams whilst in the CG it was by 14 surgeons in six teams. In the TG more TURBTs were carried out by very experienced surgeons: 17/40 (43%) were done by two consultants and no TURBT was carried out by research fellows. In comparison in the CG 10/40 (25%) TURBTs were done by consultants and 6/40 (15%) TURBTs were done by two research fellows. Similar numbers of TURBTs were performed by specialist registrars in both groups 22/40 (55%). Adjuvant chemotherapy There were 35 near misses in the CG and none in the TG relating to the administration of perioperative intravesical chemotherapy. Adjuvant single shot intravesical chemotherapy was given within 6 h of completion of TURBT in 26/31 (84%) of patients in the TG and 1/23 (4%) of patients in the CG (Table 4).
Patients and presentation. Control Group
Trial Group
Age (median:range) Charlson age-comorbidity score
71 (36—92) 3 (0—11)
72.5 (39—94) 3 (0—6) median (range)
Referral details Urgent referral
26/32 (81%)
22/32 (69%)
Presentation Macrohaematuria
26/33 (79%)
36/40 (90%)
70
E.R. Ray et al.
Table 3
‘Process’ criteria near misses.
Near misses
Control Group
Trial Group
5/40 (13%) 7/40 (18%) 28/40 (70%) Median 32.5 days Range (0—286) 18
1/40 (3%) 5/40 (13%) 34/40 (85%) Median 25 days Range (5—91) 12
Time from diagnosis to TURBT
Median 9 days Range (1—85)
Median 10 days Range (1—254)
Near misses
3
2
Time from TURBT to results OPA
Median 26 days Range (13—126)
Median 17.5 days Range (6—30)
Near misses
10
3
p = 0.067 p = 0.033a
Absent or unavailable upper tract imaging or medical notes No pre-assessment
4 26/38 (68%)
2 18/40 (45%)
p = 0.675 p = 0.115
Total
61
37
p = 0.003a
Time from referral to flexible cystoscopy Not known No flexi. cystoscopy Flexi. cystoscopy done
Near misses
a
p = 0.119 p = 0.069
p = 1.000 p = 0.500
Statistically significant.
Table 4
‘Surgical’ criteria near misses.
Near misses
Control Group
Trial Group
Pre-op cytology absent Pre-operative urinalysis absent
11/40 (28%) 9/40 (23%)
3/40 (8%) 2/40 (5%)
p = 0.037a p = 0.024a
Administration of adjuvant chemotherapy No relating documentation Not given, reason not documented Given Day of TURBT (>6 h) Day 1 Total
7/38 (18%) 6/38 (16%)b 23/38 (61%)c 4/23 (17%) 18/23 (78%) 35
0/40 0/40d 31/40 (78%) 0 0 0
p < 0.001a
Absence of examination under anaesthetic (EUA) (only 33 operation notes available) Absence of histology report at 1st OPA Absence of muscle in specimen Not discussed at MDM
7/33 (21%)
3/40 (8%)
p = 0.177
1/40 (2.5%) 9/40 (23%) 18/38 (47%)
0 7/40 (18%) 0/40
p = 1.000 p = 0.781 p < 0.001a
Total
90
15
p = 0.001a
a b c d
Statistically significant. In 2 cases chemotherapy was not given but the reason was documented. In 1 case chemotherapy was given within 6 h. In 9 cases chemotherapy was not given but the reason was documented.
In the CG adjuvant chemotherapy was mostly given the day following surgery (n = 18/23 (78%)). Pathology The proportion of pathology specimens not containing detrusor muscle was similar in the two groups. For two patients in the TG the histological diagnosis was changed at the MDM: one was upgraded from G2pTa to focal CIS and one was downgraded from G2pTa with focal CIS to papillary neoplasm
of low malignant potential. Interestingly, in the CG there was no documentation of discussion at MDM for 18/32 (56%) of patients and these were counted as near misses.
Discussion This study has shown that the initiation of a clinical trial in our hospital has markedly improved the
Improving bladder cancer outcomes quality of care delivered to patients in the trial. There were statistically significant improvements in both process and surgical criteria. This study is different to previous studies on the topic. A recent Cochrane review [2] assessed studies which measured direct outcomes related to the treatment received rather than quality of care which may be considered an indirect benefit. The improvements in surgical factors may relate to the Hawthorne effect. Elton Mayo’s interpretation of research in industry was that workers who were being closely observed improved their performance: the important effect was the feeling of being studied [7,8]. In the present study the Hawthorne effect may operate at various interfaces: nurses may be performing better by ensuring that urine is collected; patients may be performing better by being more likely to keep their appointments; surgeons may be carrying out more careful TURBT. In essence, the Hawthorne effect could lead to fewer near misses due to improvements in both clinician and patient performance. Alternatively, the existence of an explicit trial protocol stating, for example, that post-operative mitomycin C should be given within 6 h of TURBT, may be the reason for better performance. In 2004 patients newly diagnosed with bladder cancer were managed by any one of six teams at Guy’s Hospital. In 2005 the initiation of the PDD trial led to the reorganisation of bladder cancer care in the department. The trial protocol stipulated that all eligible patients be under the care of one of two consultants: this arrangement was felt to be more practical and was the best way of ensuring that the surgeons were all highly skilled at PDDassisted TURBT. This reorganisation itself may have led to a reduction in near misses and better quality of care, although it would have been interesting to know what the near misses were for the two bladder cancer teams alone, compared to the six overall, before the trial in 2004, as this may have introduced a bias. The trial has not led to more rapid admission to hospital for TURBT after diagnosis. Standards were excellent in 2004 and remain so. More patients in the TG had their operation performed by a consultant urologist (43% versus 25%) however, and no trial patients had surgery by a research registrar. This is an important change because it has been suggested that the observed variability in recurrence rates in NMIBC is related to the quality of TURBT and therefore the experience of the surgeon [9]. Administrative errors have undoubtedly been reduced because the supervision of trial patients has been in the hands of one researcher. Delays in
71 care post-TURBT have been improved. All patients in the trial were seen in clinic with histology results by 30 days following surgery. In the CG one patient had no report to discuss by the time of follow-up (documented in the clinic letter) and three patients were seen more than 100 days after surgery with no documentation of a reason why. The difference in time from TURBT to results OPA was statistically significant (p = 0.033), but it is possible that prospective data collection for the trial patients and retrospective data collection for the control patients has introduced a mode effect. Not all the improvements identified in this study relate to the organisation of the trial. Patients are referred for consideration for trial entry after the diagnosis of a new bladder cancer. Improvements in time to referral are therefore outside the remit of the trial. Additionally, there are likely to be other benefits for patients in the trial that cannot be measured by near miss criteria. A patient satisfaction questionnaire would have been be a good adjunct to this near miss study but would only have been valid if taken prospectively for both groups.
Conclusion The initiation of a bladder cancer trial at Guy’s hospital, which led to a reorganisation of the management of bladder cancer, has manifestly improved the standard of care for all patients in the trial. The indirect benefits of being in a trial need to be more strongly communicated to patients. These benefits could potentially be made available to patients outside a trial setting by using a treatment protocol; limiting the number of surgeons; and increasing the seniority of surgeons. Rigorous audit may even produce a Hawthorne effect in the non-research setting. The recruitment of patients into trials is potentially a valuable driver of quality improvement.
Conflict of interest The authors declare that there are no conflicts of interest.
Acknowledgement We thank all the urologists who have referred patients into this study.
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References [1] Wright J, Whelan TJ, Schiff S, Dubois S, Crooks D, Haines PT, et al. Why cancer patients enter randomized clinical trials: exploring the factors that influence their decision. J Clin Oncol 2004;22:4312—8. [2] Vist GE, Hagen KB, Devereaux PJ, Bryant D, Oxman AD. Outcomes of patients who participate in randomised controlled trials compared to similar patients receiving similar interventions who do not participate. Cochrane Database Syst Rev 2007. [3] National patient safety agency: doing less harm. Department of Health. [4] ISRCTN 14275387. 2-9-2005. Ref Type: Internet Communication.
[5] Singh R, Saleemi A, Walsh K, Popert R, O’Brien T. Near misses in bladder cancer—–an airline safety approach to urology. Ann R Coll Surg Engl 2003;85:378—81. [6] Babjuk M, Oosterlinck W, Sylvester R, Kaasinen E, Bohle A, Palou J. EAU: Guidelines on T1Ta (non-muscle invasive) bladder cancer, Chapter 1; 2008 edition. [7] Hsueh Y. The Hawthorne experiments and the introduction of Jean Piaget in American industrial psychology, 1929—1932. Hist Psychol 2002;5:163—89. [8] Mayo E. The human problems of an industrial civilization. New York: MacMillan; 1933. Chapter 3. [9] Brausi M, Collette L, Kurth K, van der Meijden AP, Oosterlinck W, Witjes JA, et al. Variability in the recurrence rate at first follow-up cystoscopy after TUR in stage Ta T1 transitional cell carcinoma of the bladder: a combined analysis of seven EORTC studies. Eur Urol 2002;41:523—31.
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