Trials of surgery for stress incontinence thoughts on the Humpty Dumpty principle

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1 BJOG: an International Journal of Obstetrics and Gynaecology October 2002, Vol. 109, pp Trials of surgery for stress incontinence thoughts on the Humpty Dumpty principle In Lewis Carroll s Through the Looking Glass and what Alice found there, the character Humpty Dumpty says, When I use a word, it means just what I choose it to mean neither more nor less 1. Over the last 25 years, Richard Turner-Warwick has often cited this principle in emphasising the importance of consistent terminology in clinical research 2. The International Continence Society, through its Standardisation Committee, has gone a long way towards ensuring the standardisation of terminology and methodology in the area of lower urinary tract function and dysfunction, and their recently revised recommendations are most welcome 3. The definition of cure of incontinence, however, particularly in respect of the outcome of continence surgery, remains problematic. In a recent editorial, Blaivas 4 points out the simple truth that words are the...principal means by which we communicate with one another. Some words convey their meaning with uniform precision and understanding; others lead to confusion and controversy. The word cure in the context of urinary incontinence is perhaps in the forefront of this controversy. Recent systematic reviews have emphasised the poor quality of surgical research in this area, and the small number of truly randomised trials of surgery for stress urinary incontinence 5 7. Black and Downs 6 emphasised that much of the variation in findings between surgical studies may be due to methodological differences rather than differences in effectiveness of the procedures. These authors also pointed out the inherent problems of interpreting surgical literature due to differences in case definition, confounding variables in non-randomised trials, variation in surgical technique both between and within studies, external validity or the extent to which findings may be generalised to the population, variation in follow up and outcome assessment and finally statistical power 6. The Tension-Free Vaginal Tape (TVT)* procedure 8 and Burch colposuspension 9 have recently been compared in a multicentre randomised comparative trial (RCT) in UK and Eire 10. The results of this trial (referred to here as the UK TVT RCT ) provide an opportunity to investigate * The terms Tension-free vaginal tape procedure and TVT procedure refer to the operation as described by Ulmsten et al. 8 ; SERNIP have used tension-free urethropexy as a generic term for such procedures. The terms Tension-free Vaginal Tape (TVT), TVT, and Gynecare TVT refer to the device used during that procedure, and are trademarks of Gynecare, a Johnson and Johnson company. D RCOG 2002 BJOG: an International Journal of Obstetrics and Gynaecology PII: S (02) several of these effects. Issues of randomisation and blinding, the most appropriate population for analysis, the definition of cure or primary outcome variable, external validity and statistical power will be considered in this commentary. Randomisation and blinding In his 1971 Rock-Carling monograph on effectiveness and efficiency in health services, Archie Cochrane 11 said When humans have to make observations there is always the possibility of bias. Effective randomisation is the key to avoiding selection bias, and is a crucial component of high quality RCTs 12. Sadly this component is often lacking, and a significant proportion of supposedly RCTs in obstetrics and gynaecology journals are not truly randomised 13. Within the UK TVT RCT randomisation was undertaken via a telephone system, which allocated trial identification number and treatment group; randomisation was computer generated using blocks of four and six, block sizes themselves being randomly ordered. Hence, the allocation was unpredictable and concealed from investigators enrolling patients. In fact, within the original randomisation procedure at the outset of this study, a fixed block length was employed, and the randomisation threatened when one of the trial data monitors innocently and inadvertently released this information to an investigator. Given that a relatively small block size had been chosen, it became easy to predict the sequence after the first few cases in any unit had been randomised. Fortunately, this procedural flaw was recognised early, and a protocol amendment was introduced before significant bias was introduced. Blinding within surgical studies is clearly complex, particularly where there are significant differences in the procedures under consideration. Blinding has been shown to be feasible in a trial of surgery for stress incontinence, as demonstrated by Carey et al. 14, in a trial of laparoscopic versus open colposuspension. Within the UK TVT RCT, it was felt that the differences in anaesthesia, incision and post-operative catheterisation regimen made attempts at blinding of patients impractical. Although all data were double entered, independently of investigating centres, staff undertaking post-operative assessments were not blinded to the procedure for logistic reasons, and were therefore vulnerable to observer bias.

2 1082 The appropriate population for study One of the frequent criticisms of surgical studies is the duration and completeness of follow up 6. The WHO International Consultation on Incontinence has recommended follow up after one to three months be looked on as short term, up to 12 months as medium term and beyond 12 months as long term 15. The initial analysis of the UK TVT RCT was undertaken at six months, with secondary analyses planned at two and five years. Given the tendency for surgical results to deteriorate with time, short term follow up studies will inevitably exaggerate the success of the procedures. It must be remembered that all of these time scales are short compared with the life expectancy of the women who tend to undergo surgery for incontinence 6. Incompleteness of follow up is an inevitable consequence of the relatively long term follow up that surgical trials require; the longer the follow up the greater the dropout rate is likely to be. One of the longest term, and most commonly quoted, follow up studies of incontinence surgery is the 10- to 20-year review of patients undergoing colposuspension, reported by Alcalay et al. 16. One hundred and nine patients operated on between 1974 and 1983 were followed up clinically and by pad-testing in 1994, with a mean cure rate at 20 years of 69% (82% for primary procedures, and 50% for secondary cases). There were however 336 patients operated on in the unit over this time period, with over two-thirds not attending for review. The concept of an intention-to-treat (ITT) analysis has to date been applied much more within pharmacologic than surgical interventions. Within most surgical studies, the assumption has been made, usually with no foundation at all, that those failing to return for follow up, or with incomplete data, have comparable success to those with complete data. Within this latter study, no attempt was made to compare non-attenders and attenders, and if one makes the assumption that non-attenders were in some way different, and therefore more appropriately considered as failures, the cure rate on an ITT basis would not be 69%, but 23%. The Consolidated Standards of Reporting Trials (CON- SORT) statement was first published in 1996, by an international group of clinical trialists, statisticians, epidemiologists and biomedical editors 17. A revised version of the statement has recently been developed and widely disseminated in the literature and on the Internet 21, along with an additional explanatory paper 12. The statement consists essentially of a checklist and flow diagram to help authors improve the quality of reporting of randomised controlled trials (RCTs). It has been widely advocated as the most appropriate way to ensure transparency and high quality reporting of RCTs 22, and evidence of the effectiveness of this approach is accumulating 23,24. The UK TVT RCT is one of the first surgical trials to adhere to these recommendations, and the CONSORT flow diagram as applied to the study is illustrated in Fig. 1. It is self-evident that the apparent cure rate for the two procedures will vary depending on the population included in the analysis (see Fig. 2). Randomised (n=344) TVT (n=175) Colposuspension (n=169) Received treatment as allocated (n=170) Withdrew consent (n=2) Declined surgery (n=1) Ineligible for trial (n=2) Received treatment as allocated (n=146) Withdrew consent (n=16) Declined surgery (n=5) Ineligible for trial (n=2) Followed up at 6 months (n=167) Lost to follow-up (n=1) Withdrew (n=2) Followed up at 6 months (n=137) Lost to follow-up (n=8) Withdrew (n=1) Completed questionnaires (n=159) Completed urodynamic investigation (n=156) Complete data available (n=152) Completed questionnaires (n=137) Completed urodynamic investigation (n=131) Complete data available (n=127) Fig. 1. CONSORT flow diagram as applied to the UK TVT RCT data 10. Reproduced with permission of the authors and publishers.

3 100% % 80% 70% 60% 50% 40% 30% 20% 10% 0% Patients randomised (344) Patients operated upon (316) Patients attending for follow-up (304) Patients with complete data (279) Fig. 2. Objective cure rates for TVT (dark grey) and colposuspension (light grey), based on negative cystometry and pad testing, for patient groups at different levels in the CONSORT flow chart. In the UK TVT RCT, a true ITT analysis is presented, including all patients randomised, and considering those women not undergoing surgery, or those with incomplete data as treatment failures; this is the only analysis that is wholly protected from bias by the randomisation process. Using the primary outcome of a negative cystometry and negative ICS 1-hour pad test (<1 g weight increase), 66% of TVT and 57% of colposuspension patients were cured. There were, however, 28 patients who underwent randomisation, but who withdrew prior to operation. Significantly more withdrew after randomisation to colposuspension (n ¼ 23) than TVT (n ¼ 5). It could be argued that using the true ITT analysis gives unfair advantage to the less invasive procedure; a modified ITT analysis including only those patients undergoing surgery might be said to protect from bias due to differential withdrawal rate prior to surgery. On this basis, the cure rates were 68% for TVT and 66% for colposuspension. Using the more conventional approach, of a per protocol analysis of only those patients with complete data would exclude a further 18 patients undergoing TVT (one of whom was lost to follow up, two of whom withdrew, and 15 of whom had incomplete data), and 19 undergoing colposuspension (eight of whom were lost to follow up, one of whom withdrew, and 10 of whom had incomplete data). This would result in an objective cure rate of 79% for both procedures. While in this study none of these differences between procedures are of statistical significance, one can see from Fig. 2 that in other circumstances the study conclusions might be radically altered by the use of the per protocol as distinct from ITT approach to analysis. The other argument for using a modified ITT analysis is that one can hardly judge the effectiveness of an operation from patients who have not actually undergone surgery. On the other hand, one might reasonably argue that a patient s decision to withdraw consent after randomisation is likely to reflect something of their views about the procedure concerned. It is of interest that more withdrew after randomisation to colposuspension than after randomisation to TVT; it is also of note that those women who withdrew had milder degrees of incontinence as judged on pre-operative pad testing. It is conceivable therefore that their decision to withdraw was an indication that, despite initially agreeing to the concept of randomisation, they felt that their symptoms were not sufficient to justify the more major intervention. If this were the case, the use of the true ITT analysis could be seen as entirely appropriate. Whatever the rights and wrongs of this argument, we would certainly advocate the more widespread use of the CONSORT recommendations and checklist

4 1084 within the reporting of surgical trials in particular; only by this means can editors, reviewers and readers identify such potential sources of bias. The definition of cure The Department of Health review of good practice in continence services charges that NHS Trusts should ensure that effective surgical procedures for incontinence are undertaken and that they are carried out by surgeons who do an adequate workload to maintain their expertise and achieve good outcomes for their patients 25. A report on health outcome indicators in respect of urinary incontinence, recently commissioned by the Department of Health, identifies a number of measures of outcome of relevance to surgical treatment 26. These include: the percentage of anterior repair procedures undertaken in a population of women undergoing surgery for incontinence without vaginal prolapse; the rate of re-operation in a hospital provider unit population within two years following surgical treatment for urinary incontinence; and changes in urinary symptoms from before treatment to six months afterwards within a provider unit population receiving treatment for urinary incontinence. While one would have little argument about the relevance of these indicators to health policymakers, and commissioners, they are not appropriate to the definition of cure within the context of a clinical trial. Recommendations regarding standards of outcome have been defined by the International Continence Society 27,28, the Urodynamics Society 29, the American Urological Association 30 and the World Health Organisation International Consultation on Incontinence 15,31. All of these groups emphasise that as incontinence itself is a multidimensional phenomenon, the outcome of treatment should be seen within various domains. These might include some or all of the following: patient s observations (i.e. symptoms); quantification of symptoms (e.g. frequency/volume charting, or urine loss by pad testing); the physician s observations and objective measurements (e.g. urodynamic investigations); quality of life measurements (e.g. using generic, condition-specific or dimension-specific questionnaires); and socio-economic evaluations (e.g. cost effectiveness analysis) 28. All of these domains were employed as either primary or secondary outcomes within the UK TVT RCT. In emphasising the need for a multidimensional approach to the evaluation of continence, each of these reports indicates that no single outcome measure is adequate to summarise the effects of treatment. As a corollary, none of the consensus reports from these groups gives a clear statement as to the most relevant single variable, or combination of variables to act as a primary outcome measure in trials of therapeutic intervention. The emphasis on urodynamic outcome measures has increased over the last two decades, based on the assumption that only physician determined variables could be looked on as truly objective. In his otherwise excellent systematic review of surgery for genuine stress incontinence, Jarvis states Although subjective assessment of cure may be satisfactory in clinical practice, it is clearly unsatisfactory for scientific assessment. Furthermore, he indicates that An objective method of assessment is defined as cure assessed by urodynamic assessment (sic) 5. Although the arguments in favour of subjective or objective measures of primary outcome continue, most surgical series with objective outcome measures use a single urodynamic variable to define cure; most commonly this has been the absence of urodynamic stress incontinence on cystometry, or a negative pad test. Using these measures in the ITT analysis within the UK TVT RCT would have resulted in cure rates between 65% and 81% (see Fig. 3), which would be comparable with existing literature 7,32. The primary outcome within the trial protocol, however, was based on a combined objective variable using the absence of genuine stress on cystometry and a negative ICS 1-hour pad test (i.e. in order to be looked on as cured patients had to satisfy both criteria). Because these tests do not necessarily identify the same patients as being wet, the cure rates on this basis were only 66% for TVT and 57% for colposuspension. Subjective cure was one of the secondary trial outcomes, and this calculated for both stress leakage and any leakage from the responses to the Bristol Female Lower Urinary Tract Symptoms (BFLUTS) questionnaire, an incontinence specific health related quality of life instrument 33. The number of patients reporting cure of stress incontinence was in fact quite consistent with the primary outcome variable, at 59% for TVT and 53% for colposuspension. The numbers reporting complete freedom from leakage under any circumstances were substantially lower at 36% and 28%, respectively, and the combined objective and subjective cure was only 26% for both procedures. A recent statement on terminology of pelvic floor disorders from the National Institutes of Health (NIH) emphasises the important distinction between the symptom of stress urinary incontinence, the sign of stress incontinence and the urodynamically defined condition of stress incontinence 34. This group defines cure in respect of stress incontinence as the resolution of the symptom of incontinence, the resolution of the sign of stress incontinence (negative cough stress test undertaken with a full bladder) and the absence of new symptoms or side effects. In this latter context, the report mentions specifically: new symptoms of frequency, urgency or urge incontinence, with or without urodynamic changes of detrusor over activity; change in sexual function; development or worsening pelvic organ prolapse; adverse effect on bowel function; onset of urinary infections; and surgical complications. Accepting that a very broad definition of complications/adverse events/ serious adverse events was employed within the UK TVT RCT, the cure rates within this study based on the NIH definition were 9% (TVT) and 6% (colposuspension)!

5 % 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Cystometry Pad test CMG + Pad 'No stress leakage' 'No leakage' Objective + subjective Patient satisfaction Fig. 3. Cure rates in ITT analysis, based on various definitions of cure, for TVT (dark grey) and colposuspension (light grey). Thus, including all patients randomised in the UK TVT RCT, and considering missing data as treatment failure, cure rates in this study vary between 9% and 81% for one procedure, and between 6% and 68% for the other, depending on the definition of cure. While none of these cure rates indicate a statistically significant difference between the procedures at six months, one must surely ask which of these definitions is the most appropriate to define the outcome of surgery for stress incontinence? This begs the question as to what is the purpose of outcome measures at all. In this context it is partly, as in the study under discussion, to compare one procedure with another, and partly to compare our own results with those of others; finally and perhaps most importantly, it is to allow us to counsel our patients effectively, realistically and honestly. Whatever outcomes may seem appropriate in the first of these contexts may not necessarily be of interest in the last. From a postal questionnaire survey of medical staff, continence nurses and incontinent patients, Tincello and Alfirevic 35 found that subjective measures and improvement in quality of life were regarded by all groups as the most important outcomes. The Department of Health has suggested that a measure of patient satisfaction at six months following surgery for incontinence is not only a desirable indicator of outcome in itself 26, but that care which is less satisfactory is also likely to be less effective 36. Within the UK TVT RCT, despite the apparently low success rates, patient satisfaction was high, with 83% of TVT patients and 70% of colposuspension patients indicating that they were either satisfied or highly satisfied with the outcome of surgery, and would recommend the same procedure to a friend or relative with the same condition (ITT analysis). If one includes only those patients who actually underwent surgery, these figures were 85% and 82%, respectively. Although much of the literature relating to colposuspension indicates a cure rate of 85% to 90%, studies giving consideration to both cure and complications have reported 44% and 58% of patients to be fully continent and complication free following surgery 37,38. In a prospective cohort study of women treated by a range of incontinence procedures in 18 hospitals in the North Thames health regions, Black et al. found that while the surgeon was satisfied with the outcome in 85% of cases, and 66% of patients felt the outcome met their expectations and would recommend the operation to a friend, only 28% were fully continent 39,40, based on a symptom severity index 41. A subsequent analysis of these data looking more specifically at colposuspension, needle suspension and anterior colporrhaphy found cure rates of 34%, 13% and 19%, respectively, at 12 months post-operatively, with one or more complications occurring within the year following surgery in 69%, 80% and 59%, respectively 42. External validity The random allocation of patients in a RCT, as discussed earlier, is an issue of internal validity or comparability of trial groups. The random selection of patients for inclusion

6 1086 in a study is an issue of external validity or generalisability of the study findings 15. The use of broad inclusion criteria within a trial will increase the generalisability of the results (i.e. will ensure that the findings can be extrapolated from the study participants to others with the same condition). In designing a trial however, one has to reach a reasonable balance between generalisability and protocol control. The studies of Black et al. 39,40,42 cited above included all women undergoing surgery for stress incontinence managed by 49 surgeons from 18 hospitals in two health regions. Their study has been heavily criticised on the grounds that it included some patients who underwent pre-operative urodynamic investigation and others who did not, the initial report at least included several different operative procedures allocated in non-random fashion, and reported together, and no consideration was given to known confounding variables The trial design was, however, intentionally pragmatic to allow the evaluation of the effectiveness of surgery in typical patients treated by surgeons working in typical settings; as such, their study represents the clearest model of generalisability. In the UK TVT RCT, we sought to achieve a much greater degree of rigour within the protocol, but at the same time wished to maintain a measure of external validity. For this reason, the 14 trial centres included a mix of university teaching hospitals (n ¼ 7) and district general hospitals (n ¼ 7), of urologists (n ¼ 2), general gynaecologists (n ¼ 5) and urogynaecolgists (n ¼ 7), and a range of unit size and workload (recruitment numbers 6 to 52). The concept of external validity implies that, if the trial outcome indicates that two-thirds of patients achieve objective cure and freedom from symptoms of stress incontinence, the typical patient in the typical secondary care setting might expect the same. In order to check the consistency of results between groups, various subanalyses were undertaken. There was no difference in cure rate between colposuspension and TVT between urologists and gynaecologists, between university teaching and district general hospitals, between consultants and trainees or between early and late recruits to trial. There was, however, wide variation in cure rate between centres with objective cure rates between 0% and 90% for TVT and 0% and 92% for colposuspension in the ITT analysis (see Fig. 4). There was an unavoidable difference in surgeons expertise in the two surgical procedures. All had considerable experience of colposuspension; while all had undergone similar training in the TVT procedure, they had variable experience prior to commencing recruitment. The use of an ITT analysis with non-attenders considered as failures clearly impacts on the variation between centres; a small dropout rate in a centre recruiting small numbers of patients has a considerable impact on cure rate. Even a per protocol analysis, assuming that non-attenders were the same as attenders, however, shows a range of cure rates from 33% to 100% for TVT and from 0% to 100% for colposuspension. Only two centres showed cure rates in excess of 70% for both procedures. The only association that we identified as a possible contributor to this variation was the unit recruitment number. Centres recruiting up to 20 patients in the trial had average objective cure rates of 54% for TVT and 36% for colposuspension; those recruiting between 21 and 30 patients had cure rates of 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% n y w v p u q t r o s l m x z Centre code Fig. 4. Objective cure rate in ITT analysis by trial centre for TVT (dark grey) and colposuspension (light grey).

7 % and 71% and those recruiting over 30 patients had cure rates of 84% and 77%, respectively. While it must be conceded that the effect of dropouts on an ITT analysis is greater on units recruiting small numbers of patients, it may nevertheless be the case that there is a minimum workload consistent with optimal surgical outcome. The recommendation of the Department of Health, that effective surgical procedures for incontinence should be undertaken by surgeons who do an adequate volume to maintain their expertise to achieve good outcomes, may therefore find some justification in these data 25. It must equally be remembered that patient satisfaction is deemed an important outcome measure 26. On the ITT analysis, patient satisfaction was found in 72% to 100% of TVT patients, and 33% to 100% of colposuspension patients in the different collaborating units; the per protocol analysis indicated patient satisfaction in over 75% of patients by both procedures. However one interprets these data, there is a clear message about the external validity of the results. The main conclusions from this trial were that the TVT procedure is as effective as colposuspension for the treatment of primary genuine stress incontinence in the short term and that recovery from surgery was more rapid after TVT than colposuspension. While these conclusions may be valid for the study population as a whole, they cannot necessarily be interpolated to individual collaborating trial centres, less still extrapolated to others. The argument for local or personal audit of surgical outcomes as a means of informing patient counselling is clearly made. Statistical power Studies involving quantitative data analysis should obviously be subjected to sample size calculation in the planning stage. The sample size calculation performed within the UK TVT RCT was based on systematic review suggesting a cure rate of 90% for colposuspension 5, and on the assumption that a 10% difference in cure rate between the two procedures would be clinically important. To detect this level of difference with 80 90% power would have required 196 to 262 patients in each arm of the trial. Actual trial numbers often represent a compromise between the statistical ideal, and a pragmatic total based on available patients and a realistic recruitment period. The pragmatic target within this trial was actually 436 patients, which would have given a statistical power of 85% to detect the 10% difference in outcome. Even the actual recruitment achieved, 344 patients, on the same assumptions, should still have had a 70% power, substantially greater than previous surgical trials for incontinence. It must be remembered however that sample size calculation is an a priori process, whereas statistical power calculation is undertaken post hoc, and previous assumptions must therefore be revised on the basis of known outcomes. Given that the objective cure found for colposuspension (57%) was lower than expected from previous literature, the numbers recruited would give only 50% power to detect a 10% difference, or 80% power to detect a 15% difference in cure rate. While the UK TVT RCT is one of the largest RCTs in the literature on this subject, and it remains true to say that a difference in cure rate between the procedures was not demonstrated, the statistical power even of this study is limited. The numbers recruited are certainly not sufficient to assume equivalence. The UK TVT RCT has been looked on not only as one of the largest, but also one of the best designed trials published to date, in relation to incontinence surgery; it would be inappropriate for this commentator to gainsay that assessment! This further analysis and commentary on the trial data will hopefully, however, serve to illustrate some of the logistic and methodological pitfalls of surgical trial design, analysis and interpretation. Disraeli is reported to have said There are three kinds of lies lies, damned lies, and statistics. Mark Twain made the exhortation Get your facts first then you can distort them as much as you please. It appears that in the area of continence surgery the distortion has all too often gone on subconsciously, and as a result, much of what is published as statistical fact might better be placed in Disraeli s alternative categories. That s a great deal to make one word mean, Alice said in a thoughtful tone. When I make a word do a lot of work like that said Humpty Dumpty, I always pay it extra. 1 Paul Hilton Royal Victoria Infirmary, Newcastle upon Tyne, UK References 1. Carroll L. Through the looking glass and what Alice found there. The Complete Works of Lewis Carroll. New York: The Modern Library, 1936 (Republished from the original text of 1871): Turner Warwick R, Whiteside G. About it. Urol Clin North Am 1979;6(1): Abrams P, Cardozo L, Fall M, et al. Standardisation of terminology of lower urinary tract function: report from the Standardisation Subcommittee of the International Continence Society. Neurourol Urodyn 2002;21: Blaivas JG. Defining words: overactive bladder. Neurourol Urodyn 1999;18(5): Jarvis GJ. Surgery for genuine stress incontinence. Br J Obstet Gynaecol 1994;101(5): Black NA, Downs SH. The effectiveness of surgery for stress incontinence in women: a systematic review. Br J Urol 1996; 78(4): Leach GE, Dmochowski RR, Appell RA, et al. 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Br J Urol 1987;60: Eriksen B, Hagen B, Eik-Nes S, Molne K, Mjolnerod D, Romslo I. Long-term effectiveness of the Burch colposuspension in female urinary stress incontinence. Acta Obstet Gynecol Scand 1990;69: Black NA, Bowling A, Griffiths JM, Pope C, Abel PD. Impact of surgery for stress incontinence on the social lives of women. Br J Obstet Gynaecol 1998;105(6): Black N, Griffiths J, Pope C, Bowling A, Abel P. Impact of surgery for stress incontinence on morbidity: cohort study. BMJ 1997;315(7121): Black N, Griffiths J, Pope C. Development of a symptom severity index and a symptom impact index for stress incontinence in women. Neurourol Urodyn 1996;15(6): Hutchings A, Black NA. Surgery for stress incontinence: a nonrandomised trial of colposuspension, needle suspension and anterior colporrhaphy. Eur Urol 2001;39(4): Lose G, Walter S. Impact of surgery for stress incontinence on morbidity. Pragmatic randomised trial is required. BMJ 1998;317(7151): (Discussion 144). 44. Duckett JR. Impact of surgery for stress incontinence on morbidity. Colposuspension has highest cure rates. BMJ 1998;317(7151): (Discussion 144). 45. O Connor RA. Impact of surgery for stress incontinence on morbidity. Treatment needs to be based on objective assessment rather than on symptoms. BMJ 1998;317(7151): (Discussion 144). 46. James M, Abrams P, Gujral S. Impact of surgery for stress incontinence on morbidity. Patients should be told hospital results and allowed to choose where they want surgery. BMJ 1998;317(7151): (Discussion 144). 47. Khullar V, Cardozo L, Boos K, Bidmead J, Kelleher C. Impact of surgery for stress incontinence on morbidity. Effects of confounding variables on outcomes of incontinence surgery must be considered. BMJ 1998;317(7151):143 (Discussion 144). 48. O Connor RA. Impact of surgery for stress incontinence on the social lives of women. Br J Obstet Gynaecol 1999;106(6): Khullar V, Cardozo L, McLellan A, Bidmead J, Kelleher C. Impact of surgery for stress incontinence on the social lives of women. Br J Obstet Gynaecol 1999;106(3):