Best practice considerations on the assessment of robotic assisted surgical systems: results from an international consensus expert panel.

BACKGROUND: Health technology assessments (HTAs) of robotic assisted surgery (RAS) face several challenges in assessing the value of robotic surgical platforms. As a result of using different assessment methods, previous HTAs have reached different conclusions when evaluating RAS. While the number of available systems and surgical procedures is rapidly growing, existing frameworks for assessing MedTech provide a starting point, but specific considerations are needed for HTAs of RAS to ensure consistent results. This work aimed to discuss different approaches and produce guidance on evaluating RAS. METHODS: A consensus conference research methodology was adopted. A panel of 14 experts was assembled with international experience and representing relevant stakeholders: clinicians, health economists, HTA practitioners, policy makers, and industry. A review of previous HTAs was performed and seven key themes were extracted from the literature for consideration. Over five meetings, the panel discussed the key themes and formulated consensus statements. RESULTS: A total of ninety-eight previous HTAs were identified from twenty-five total countries. The seven key themes were evidence inclusion and exclusion, patient- and clinician-reported outcomes, the learning curve, allocation of costs, appropriate time horizons, economic analysis methods, and robotic ecosystem/wider benefits. CONCLUSIONS: Robotic surgical platforms are tools, not therapies. Their value varies according to context and should be considered across therapeutic areas and stakeholders. The principles set out in this paper should help HTA bodies at all levels to evaluate RAS. This work may serve as a case study for rapidly developing areas in MedTech that require particular consideration for HTAs.

Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism.

Male hypogonadism (MH) is a common endocrine disorder. However, uncertainties and variations in its diagnosis and management exist. There are several current guidelines on testosterone replacement therapy that have been driven predominantly by single disciplines. The Society for Endocrinology commissioned this new guideline to provide all care providers with a multidisciplinary approach to treating patients with MH. This guideline has been compiled using expertise from endocrine (medical and nursing), primary care, clinical biochemistry, urology and reproductive medicine practices. These guidelines also provide a patient perspective to help clinicians best manage MH.

Partial ablation versus radical prostatectomy in intermediate-risk prostate cancer: the PART feasibility RCT.

BACKGROUND: Prostate cancer (PCa) is the most common cancer in men in the UK. Patients with intermediate-risk, clinically localised disease are offered radical treatments such as surgery or radiotherapy, which can result in severe side effects. A number of alternative partial ablation (PA) technologies that may reduce treatment burden are available; however the comparative effectiveness of these techniques has never been evaluated in a randomised controlled trial (RCT). OBJECTIVES: To assess the feasibility of a RCT of PA using high-intensity focused ultrasound (HIFU) versus radical prostatectomy (RP) for intermediate-risk PCa and to test and optimise methods of data capture. DESIGN: We carried out a prospective, multicentre, open-label feasibility study to inform the design and conduct of a future RCT, involving a QuinteT Recruitment Intervention (QRI) to understand barriers to participation. SETTING: Five NHS hospitals in England. PARTICIPANTS: Men with unilateral, intermediate-risk, clinically localised PCa. INTERVENTIONS: Radical prostatectomy compared with HIFU. PRIMARY OUTCOME MEASURE: The randomisation of 80 men. SECONDARY OUTCOME MEASURES: Findings of the QRI and assessment of data capture methods. RESULTS: Eighty-seven patients consented to participate by 31 March 2017 and 82 men were randomised by 4 May 2017 (41 men to the RP arm and 41 to the HIFU arm). The QRI was conducted in two iterative phases: phase I identified a number of barriers to recruitment, including organisational challenges, lack of recruiter equipoise and difficulties communicating with patients about the study, and phase II comprised the development and delivery of tailored strategies to optimise recruitment, including group training, individual feedback and 'tips' documents. At the time of data extraction, on 10 October 2017, treatment data were available for 71 patients. Patient characteristics were similar at baseline and the rate of return of all clinical case report forms (CRFs) was 95%; the return rate of the patient-reported outcome measures (PROMs) questionnaire pack was 90.5%. Centres with specific long-standing expertise in offering HIFU as a routine NHS treatment option had lower recruitment rates (Basingstoke and Southampton) - with University College Hospital failing to enrol any participants - than centres offering HIFU in the trial context only. CONCLUSIONS: Randomisation of men to a RCT comparing PA with radical treatments of the prostate is feasible. The QRI provided insights into the complexities of recruiting to this surgical trial and has highlighted a number of key lessons that are likely to be important if the study progresses to a main trial. A full RCT comparing clinical effectiveness, cost-effectiveness and quality-of-life outcomes between radical treatments and PA is now warranted. FUTURE WORK: Men recruited to the feasibility study will be followed up for 36 months in accordance with the protocol. We will design a full RCT, taking into account the lessons learnt from this study. CRFs will be streamlined, and the length and frequency of PROMs and resource use diaries will be reviewed to reduce the burden on patients and research nurses and to optimise data completeness. TRIAL REGISTRATION: Current Controlled Trials ISRCTN99760303. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 52. See the NIHR Journals Library website for further project information.

Are clinical guidelines designed according to guidelines? Cross-sectional assessment of quality and transparency of clinical guidelines in urology.

PURPOSE: Guidelines and recommendations become increasingly important in clinical urologic practice. This study aims to inform clinicians using guidelines on how to evaluate the quality of the methodology and transparency of these documents. METHODS: The guidelines on management of castration-resistant prostate cancer of the American Urology Association, European Association of Urology, National Comprehensive Cancer Network, National Institute for Health and Care Excellence, European Society of Medical Oncology were reviewed using the AGREE-II tool (Appraisal of Guidelines for Research and Evaluation). We reported and compared the domain scores for the domains 1 scope and purpose, 2 stakeholder involvement, 3 rigor of development, 4 clarity of presentation, 5 applicability, and 6 editorial independence (100% indicates highest-best quality score). RESULTS: The domains evaluated highest and with lowest variability were 'editorial independence' (92% {88-95%}) and 'clarity of presentation' (83% {72-90%}), while the domains with the lowest scores and most variability were 'stakeholder involvement' (56% {36-79%}) and 'applicability' (40% {30-63%}). Length and extent of detail of guidelines vary considerably, each with its own strengths and limitations and adapted to target users. Standard external review using AGREE criteria may be preferable. A formal search strategy was not performed. Findings may be outdated by guidelines' updates. CONCLUSIONS: Clinicians using practice guidelines need to be aware of the different domains of methodology and transparency used to assess the quality of guidelines contents and recommendations. Urologists increasingly use guidelines for support in evidence-based recommendations in clinical practice. It is very important to know how to assess these documents. This study applies standard criteria to compare the design and background of different available guidelines on prostate cancer no longer responding to hormonal treatment.

Symptoms, unmet needs, psychological well-being and health status in survivors of prostate cancer: implications for redesigning follow-up.

OBJECTIVE: To explore ongoing symptoms, unmet needs, psychological wellbeing, self-efficacy and overall health status in survivors of prostate cancer. PATIENTS AND METHODS: An invitation to participate in a postal questionnaire survey was sent to 546 men, diagnosed with prostate cancer 9-24 months previously at two UK cancer centres. The study group comprised men who had been subject to a range of treatments: surgery, radiotherapy, hormone therapy and active surveillance. The questionnaire included measures of prostate-related quality of life (Expanded Prostate cancer Index Composite 26-item version, EPIC-26); unmet needs (Supportive Care Needs Survey 34-item version, SCNS-SF34); anxiety and depression (Hospital Anxiety and Depression Scale, HADS), self-efficacy (modified Self-efficacy Scale), health status (EuroQol 5D, EQ-5D) and satisfaction with care (questions developed for this study). A single reminder was sent to non-responders after 3 weeks. Data were analysed by age, co-morbidities, and treatment group. RESULTS: In all, 316 men completed questionnaires (64.1% response rate). Overall satisfaction with follow-up care was high, but was lower for psychosocial than physical aspects of care. Urinary, bowel, and sexual functioning was reported as a moderate/big problem in the last month for 15.2% (n = 48), 5.1% (n = 16), and 36.5% (n = 105) men, respectively. The most commonly reported moderate/high unmet needs related to changes in sexual feelings/relationships, managing fear of recurrence/uncertainty, and concerns about the worries of significant others. It was found that 17% of men (51/307) reported potentially moderate-to-severe levels of anxiety and 10.2% (32/308) reported moderate-to-severe levels of depression. The presence of problematic side-effects was associated with higher psychological morbidity, poorer self-efficacy, greater unmet needs, and poorer overall health status. CONCLUSION: While some men report relatively few problems after prostate cancer treatment, this study highlights important physical and psycho-social issues for a significant minority of survivors of prostate cancer. Strategies for identifying those men with on-going problems, alongside new interventions and models of care, tailored to individual needs, are needed to improve quality of life.

Assessment of required nodal yield in a high risk cohort undergoing extended pelvic lymphadenectomy in robotic-assisted radical prostatectomy and its impact on functional outcomes.

OBJECTIVES: To establish a minimal lymph node yield (LNY) necessary for accurate staging in a high risk cohort, since no consensus exists as to the optimal extent of pelvic lymph node dissection (PLND) needed during radical prostatectomy in high risk patients. To investigate the impact of an extended PLND on urinary and sexual function. PATIENTS AND METHODS: In all, 760 men underwent robotic-assisted radical prostatectomy from January 2010 to May 2011 by a single surgeon (AKT). Low and intermediate risk groups (as defined by the D'Amico classification) underwent a minimum of a limited PLND (obturator/external iliac packets) and high risk patients underwent an extended PLND (as limited plus hypogastric, triangle of Marcille and common iliac packets up to the level of the ureteric crossing). In order to analyse LNY for staging purposes, the high risk group (n = 82) was subdivided into patients with ≥13 LNY vs <13 LNY and the incidence of lymph node (LN) invasion was compared between these groups. To study the impact of extended PLND on functional outcomes, we evaluated patients from our total cohort who were preoperatively potent (Sexual Health Inventory for Men ≥17), continent and who received bilateral nerve-sparing surgery. Return to potency at 26 weeks postoperatively was defined as a score of ≥3 on questions 2 and 3 of the Sexual Health Inventory for Men questionnaire, and continence was defined as zero pads per day or one pad for security per day. RESULTS: Median LNYs in the low, intermediate and high risk groups were (interquartile range [IQR]) 5 (2-10), 7 (3-12) and 13 (6-20) (P < 0.001); LN positivity was 0% (0 of 309), 0.8% (3 of 369) and 13.4% (11 of 82) in the three respective groups (P < 0.001). Median LNYs (IQR) among the high risk LN positive and negative patients were 20 (13-22) and 11 (5-18) (P = 0.05); 5% of the patients had positive LNs in the <13 LNY group vs 21% of patients in the >13 LNY group (P = 0.036). Median (IQR) console time was significantly different, at 120 min (95-137) for the ≥13 LNY group vs 100 min (85-120) for the <13 LNY group (P = 0.04). Among patients who fitted the inclusion criteria for functional outcomes (n = 561), 55.2% (16 of 29) with ≥20 LNs removed recovered potency at a median follow-up of 6 months postoperatively vs 70% of patients with <20 LNs (301 of 430) (P = 0.020). There was no significant difference in continence recovery between the groups. CONCLUSIONS: High risk patients should undergo an extended dissection with at least 13 LNs removed for accurate staging. Extended PLND with LNYs of ≥20 is associated with worse potency outcomes. With LN positivity occurring rarely in low risk patients, extended PLND may be of little oncological benefit but with significant functional compromise in this cohort.

Biobanking after robotic-assisted radical prostatectomy: a quality assessment of providing prostate tissue for RNA studies.

BACKGROUND: RNA quality is believed to decrease with ischaemia time, and therefore open radical prostatectomy has been advantageous in allowing the retrieval of the prostate immediately after its devascularization. In contrast, robotic-assisted laparoscopic radical prostatectomies (RALP) require the completion of several operative steps before the devascularized prostate can be extirpated, casting doubt on the validity of this technique as a source for obtaining prostatic tissue. We seek to establish the integrity of our biobanking process by measuring the RNA quality of specimens derived from robotic-assisted laparoscopic radical prostatectomy. METHODS: We describe our biobanking process and report the RNA quality of prostate specimens using advanced electrophoretic techniques (RNA Integrity Numbers, RIN). Using multivariate regression analysis we consider the impact of various clinicopathological correlates on RNA integrity. RESULTS: Our biobanking process has been used to acquire 1709 prostates, and allows us to retain approximately 40% of the prostate specimen, without compromising the histopathological evaluation of patients. We collected 186 samples from 142 biobanked prostates, and demonstrated a mean RIN of 7.25 (standard deviation 1.64) in 139 non-stromal samples, 73% of which had a RIN ≥ 7. Multivariate regression analysis revealed cell type--stromal/epithelial and benign/malignant--and prostate volume to be significant predictors of RIN, with unstandardized coefficients of 0.867(p = 0.001), 1.738(p < 0.001) and -0.690(p = 0.009) respectively. A mean warm ischaemia time of 120 min (standard deviation 30 min) was recorded, but multivariate regression analysis did not demonstrate a relationship with RIN within the timeframe of the RALP procedure. CONCLUSIONS: We demonstrate the robustness of our protocol--representing the concerted efforts of dedicated urology and pathology departments--in generating RNA of sufficient concentration and quality, without compromising the histopathological evaluation and diagnosis of patients. The ischaemia time associated with our prostatectomy technique using a robotic platform does not negatively impact on biobanking for RNA studies.

The changing face of medical negligence law: from Bolam to Bolitho.

The Bolam test was the standard by which medical negligence cases were judged. However, recently, the Bolitho case has resulted in a shift away from Bolam, with significant effects for all future negligence suits. Doctors need to have a thorough understanding of these issues in order to practice successfully in the current litiginous climate.