Pragmatic methods for reviewing exceptionally large bodies of evidence: systematic mapping review and overview of systematic reviews using lung cancer survival as an exemplar.

INTRODUCTION: Lung cancer (LC) is the most common cause of cancer death in the world and associated with significant economic burden. We conducted a review of published literature to identify prognostic factors associated with LC survival and determine which may be modifiable and could be targeted to improve outcomes. METHODS: The exceptionally large volume of LC prognostic research required a new staged approach to reviewing the literature. This comprised an initial mapping review of existing reviews or meta-analyses, based on titles and abstracts, followed by an overview of systematic reviews evaluating factors that independently contribute to lung cancer survival. The overview of reviews was based on full text papers and incorporated a more in-depth assessment of reviews evaluating modifiable factors. RESULTS: A large volume of published systematic reviews and meta-analyses were identified, but very few focused on modifiable factors for LC survival. Several modifiable factors were identified, which are potential candidates for targeted interventions aiming to improve cancer outcomes. The mapping review included 398 reviews, of which 207 investigated the independent effect of prognostic factors on lung cancer survival. The most frequently evaluated factors were novel biomarkers (86 biomarkers in 138 reviews). Only 15 modifiable factors were investigated in 20 reviews. Those associated with significant survival improvement included normal BMI/less weight loss, good performance status, not smoking/quitting after diagnosis, good pre-treatment quality of life, small gross volume tumour, early-stage tumour, lung resection undertaken by a thoracic/cardiothoracic surgeon, care being discussed by a multidisciplinary team, and timeliness of care. CONCLUSIONS: The study utilised a novel approach for reviewing an extensive and complicated body of research evidence. It enabled us to address a broad research question and focus on a specific area of priority. The staged approach ensured the review remained relevant to the stakeholders throughout, whilst maintaining the use of objective and transparent methods. It also provided important information on the needs of future research. However, it required extensive planning, management, and ongoing reviewer training.

Development of an intervention to expedite cancer diagnosis through primary care: a protocol.

BACKGROUND: GPs can play an important role in achieving earlier cancer diagnosis to improve patient outcomes, for example through prompt use of the urgent suspected cancer referral pathway. Barriers to early diagnosis include individual practitioner variation in knowledge, attitudes, beliefs, professional expectations, and norms. AIM: This programme of work (Wales Interventions and Cancer Knowledge about Early Diagnosis [WICKED]) will develop a behaviour change intervention to expedite diagnosis through primary care and contribute to improved cancer outcomes. DESIGN & SETTING: Non-experimental mixed-method study with GPs and primary care practice teams from Wales. METHOD: Four work packages will inform the development of the behaviour change intervention. Work package 1 will identify relevant evidence-based interventions (systematic review of reviews) and will determine why interventions do or do not work, for whom, and in what circumstances (realist review). Work package 2 will assess cancer knowledge, attitudes, and behaviour of GPs, as well as primary care teams' perspectives on cancer referral and investigation (GP survey, discrete choice experiment [DCE], interviews, and focus groups). Work package 3 will synthesise findings from earlier work packages using the behaviour change wheel as an overarching theoretical framework to guide intervention development. Work package 4 will test the feasibility and acceptability of the intervention, and determine methods for measuring costs and effects of subsequent behaviour change in a randomised feasibility trial. RESULTS: The findings will inform the design of a future effectiveness trial, with concurrent economic evaluation, aimed at earlier diagnosis. CONCLUSION: This comprehensive, evidence-based programme will develop a complex GP behaviour change intervention to expedite the diagnosis of symptomatic cancer, and may be applicable to countries with similar healthcare systems.

Talking about human papillomavirus and cancer: development of consultation guides through lay and professional stakeholder coproduction using qualitative, quantitative and secondary data.

BACKGROUND: High-risk human papillomaviruses (HPVs) cause all cervical cancer and the majority of vulvar, vaginal, anal, penile and oropharyngeal cancers. Although HPV is the most common sexually transmitted infection, public awareness of this is poor. In addition, many clinicians lack adequate knowledge or confidence to discuss sexual transmission and related sensitive issues. Complex science needs to be communicated in a clear, digestible, honest and salient way. Therefore, the aim of this study was to coproduce with patients who have cancer appropriate resources to guide these highly sensitive and difficult consultations. METHODS: A matrix of evidence developed from a variety of sources, including a systematic review and telephone interviews with clinicians, supported the production of a draft list of approximately 100 potential educational messages. These were refined in face-to-face patient interviews using card-sorting techniques, and tested in cognitive debrief interviews to produce a â€Ëœfast and frugal’ knowledge tool. RESULTS: We developed three versions of a consultation guide, each comprising a clinician guidance sheet and patient information leaflet for gynaecological (cervical, vaginal, vulvar), anal or oropharyngeal cancers. That cancer could be caused by a sexually transmitted virus acquired many years previously was surprising to many and shocking to a few patients. However, they found the information clear, helpful and reassuring. Clinicians acknowledged a lack of confidence in explaining HPV, welcomed the clinician guidance sheets and considered printed information for patients particularly useful. CONCLUSION: Because of the â€Ëœshock factor’, clinicians will need to approach the discussion of HPV with sensitivity and take individual needs and preferences into account, but we provide a novel, rigorously developed and tested resource which should have broad applicability in the UK National Health Service and other health systems.

Talking about human papillomavirus and cancer: protocol for a patient-centred study to develop scripted consultations.

INTRODUCTION: Persistent infection with sexually transmitted, high-risk human papillomavirus (HPV) types is the cause of all cervical cancers and some anogenital and oropharyngeal cancers. HPV is an extremely common asymptomatic infection but little known and poorly understood by the public. Patients with HPV-related cancers have new and challenging information needs due to the complex natural history of HPV and the stigma of sexual transmission. They may ask questions that are outside the remit of the traditional cancer consultation, and there is a lack of guidance on how to counsel them. This study aims to fulfil that need by developing and testing cancer site-specific scripted consultations. METHODS AND ANALYSIS: A synthesis of findings generated from previous work, a systematic review of information-based interventions for patients with HPV-related cancers, and interviews with cancer clinicians will provide the evidence base underpinning provisional messages. These will be explored in three phases of face-to-face interviews with 75-90 purposively selected patients recruited in cancer clinics to: (1) select and prioritise the most salient messages, (2) phrase the messages appropriately in plain English and, (3) test their acceptability and usefulness. Phases 1 and 2 will draw on card-sorting methods used in website design. In phase three, we will create cancer site-specific versions of the script and test them using cognitive interviewing techniques. ETHICS AND DISSEMINATION: The study has received ethical approval. Findings will be published in a peer-reviewed journal. The final product will be cancer-specific scripted consultations, most likely in the form of a two-sided information sheet with the most important messages to be conveyed in a consultation on one side, and frequently asked questions for later reading on the reverse. However, they will also be appropriate and readily adaptable to web-based uses.

Comparative clinical effectiveness of management strategies for sciatica: systematic review and network meta-analyses.

BACKGROUND: There are numerous treatment approaches for sciatica. Previous systematic reviews have not compared all these strategies together. PURPOSE: To compare the clinical effectiveness of different treatment strategies for sciatica simultaneously. STUDY DESIGN: Systematic review and network meta-analysis. METHODS: We searched 28 electronic databases and online trial registries, along with bibliographies of previous reviews for comparative studies evaluating any intervention to treat sciatica in adults, with outcome data on global effect or pain intensity. Network meta-analysis methods were used to simultaneously compare all treatment strategies and allow indirect comparisons of treatments between studies. The study was funded by the UK National Institute for Health Research Health Technology Assessment program; there are no potential conflict of interests. RESULTS: We identified 122 relevant studies; 90 were randomized controlled trials (RCTs) or quasi-RCTs. Interventions were grouped into 21 treatment strategies. Internal and external validity of included studies was very low. For overall recovery as the outcome, compared with inactive control or conventional care, there was a statistically significant improvement following disc surgery, epidural injections, nonopioid analgesia, manipulation, and acupuncture. Traction, percutaneous discectomy, and exercise therapy were significantly inferior to epidural injections or surgery. For pain as the outcome, epidural injections and biological agents were significantly better than inactive control, but similar findings for disc surgery were not statistically significant. Biological agents were significantly better for pain reduction than bed rest, nonopioids, and opioids. Opioids, education/advice alone, bed rest, and percutaneous discectomy were inferior to most other treatment strategies; although these findings represented large effects, they were statistically equivocal. CONCLUSIONS: For the first time, many different treatment strategies for sciatica have been compared in the same systematic review and meta-analysis. This approach has provided new data to assist shared decision-making. The findings support the effectiveness of nonopioid medication, epidural injections, and disc surgery. They also suggest that spinal manipulation, acupuncture, and experimental treatments, such as anti-inflammatory biological agents, may be considered. The findings do not provide support for the effectiveness of opioid analgesia, bed rest, exercise therapy, education/advice (when used alone), percutaneous discectomy, or traction. The issue of how best to estimate the effectiveness of treatment approaches according to their order within a sequential treatment pathway remains an important challenge.

Cost-effectiveness of different strategies to manage patients with sciatica.

The aim of this paper is to estimate the relative cost-effectiveness of treatment regimens for managing patients with sciatica. A deterministic model structure was constructed based on information from the findings from a systematic review of clinical effectiveness and cost-effectiveness, published sources of unit costs, and expert opinion. The assumption was that patients presenting with sciatica would be managed through one of 3 pathways (primary care, stepped approach, immediate referral to surgery). Results were expressed as incremental cost per patient with symptoms successfully resolved. Analysis also included incremental cost per utility gained over a 12-month period. One-way sensitivity analyses were used to address uncertainty. The model demonstrated that none of the strategies resulted in 100% success. For initial treatments, the most successful regime in the first pathway was nonopioids, with a probability of success of 0.613. In the second pathway, the most successful strategy was nonopioids, followed by biological agents, followed by epidural/nerve block and disk surgery, with a probability of success of 0.996. Pathway 3 (immediate surgery) was not cost-effective. Sensitivity analyses identified that the use of the highest cost estimates results in a similar overall picture. While the estimates of cost per quality-adjusted life year are higher, the economic model demonstrated that stepped approaches based on initial treatment with nonopioids are likely to represent the most cost-effective regimens for the treatment of sciatica. However, development of alternative economic modelling approaches is required.

Patient-reported measurement of time to diagnosis in cancer: development of the Cancer Symptom Interval Measure (C-SIM) and randomised controlled trial of method of delivery.

BACKGROUND: The duration between first symptom and a cancer diagnosis is important because, if shortened, may lead to earlier stage diagnosis and improved cancer outcomes. We have previously developed a tool to measure this duration in newly-diagnosed patients. In this two-phase study, we aimed further improve our tool and to conduct a trial comparing levels of anxiety between two modes of delivery: self-completed versus researcher-administered. METHODS: In phase 1, ten patients completed the modified tool and participated in cognitive debrief interviews. In phase 2, we undertook a Randomised Controlled Trial (RCT) of the revised tool (Cancer Symptom Interval Measure (C-SIM)) in three hospitals for 11 different cancers. Respondents were invited to provide either exact or estimated dates of first noticing symptoms and presenting them to primary care. The primary outcome was anxiety related to delivery mode, with completeness of recording as a secondary outcome. Dates from a subset of patients were compared with GP records. RESULTS: After analysis of phase 1 interviews, the wording and format were improved. In phase 2, 201 patients were randomised (93 self-complete and 108 researcher-complete). Anxiety scores were significantly lower in the researcher-completed group, with a mean rank of 83.5; compared with the self-completed group, with a mean rank of 104.0 (Mann-Whitney U = 3152, p = 0.007). Completeness of data was significantly better in the researcher-completed group, with no statistically significant difference in time taken to complete the tool between the two groups. When comparing the dates in the patient questionnaires with those in the GP records, there was evidence in the records of a consultation on the same date or within a proscribed time window for 32/37 (86%) consultations; for estimated dates there was evidence for 23/37 consultations (62%). CONCLUSIONS: We have developed and tested a tool for collecting patient-reported data relating to appraisal intervals, help-seeking intervals, and diagnostic intervals in the cancer diagnostic pathway for 11 separate cancers, and provided evidence of its acceptability, feasibility and validity. This is a useful tool to use in descriptive and epidemiological studies of cancer diagnostic journeys, and causes less anxiety if administered by a researcher.

"HPV? Never heard of it!": a systematic review of girls' and parents' information needs, views and preferences about human papillomavirus vaccination.

BACKGROUND AND OBJECTIVE: Two human papillomavirus vaccines were licenced in 2006/2007 for cervical cancer prevention. National vaccination programmes for schoolgirls were subsequently introduced in some European countries, North America and Australia. To understand factors influencing vaccine uptake and to inform the development of appropriate UK educational materials, we aimed to synthesise evidence of girls' and parents' information needs, views and preferences regarding HPV vaccination. DESIGN: Systematic review and mixed method synthesis of qualitative and survey data. DATA SOURCES: Twelve electronic databases; bibliographies of included studies 1980 to August 2011. REVIEW METHODS: Two reviewers independently screened papers and appraised study quality. Studies were synthesised collaboratively using framework methods for qualitative data, and survey results integrated where they supported, contrasted or added to the themes identified. RESULTS: Twenty-eight qualitative studies and 44 surveys were included. Where vaccination was offered, uptake was high. Intention to decline was related to a preference for vaccinating later to avoid appearing to condone early sexual activity, concerns about vaccine safety and low perception of risk of HPV infection. Knowledge was poor and there were many misconceptions; participants tried to assess the potential benefits and harms of vaccination but struggled to interpret limited information about HPV in the context of existing knowledge about sexually transmitted infections and cancer. Conclusion Many girls and their parents have limited understanding to an extent that impinges on their ability to make informed choices about HPV vaccination and could impact on future uptake of cervical screening. This is a considerable challenge to those who design and provide information, but getting the messages right for this programme could help in developing patient information about other HPV related cancers.

A systematic review and meta-analysis of biological treatments targeting tumour necrosis factor α for sciatica.

PURPOSE: Systematic review comparing biological agents, targeting tumour necrosis factor α, for sciatica with placebo and alternative interventions. METHODS: We searched 21 electronic databases and bibliographies of included studies. We included randomised controlled trials (RCTs), non-RCTs and controlled observational studies of adults who had sciatica treated by biological agents compared with placebo or alternative interventions. RESULTS: We pooled the results of six studies (five RCTs and one non-RCT) in meta-analyses. Compared with placebo biological agents had: better global effects in the short-term odds ratio (OR) 2.0 (95 % CI 0.7-6.0), medium-term OR 2.7 (95 % CI 1.0-7.1) and long-term OR 2.3 [95 % CI 0.5 to 9.7); improved leg pain intensity in the short-term weighted mean difference (WMD) -13.6 (95 % CI -26.8 to -0.4), medium-term WMD -7.0 (95 % CI -15.4 to 1.5), but not long-term WMD 0.2 (95 % CI -20.3 to 20.8); improved Oswestry Disability Index (ODI) in the short-term WMD -5.2 (95 % CI -14.1 to 3.7), medium-term WMD -8.2 (95 % CI -14.4 to -2.0), and long-term WMD -5.0 (95 % CI -11.8 to 1.8). There was heterogeneity in the leg pain intensity and ODI results and improvements were no longer statistically significant when studies were restricted to RCTs. There was a reduction in the need for discectomy, which was not statistically significant, and no difference in the number of adverse effects. CONCLUSIONS: There was insufficient evidence to recommend these agents when treating sciatica, but sufficient evidence to suggest that larger RCTs are needed.

A review comparing the effectiveness of nurse-led follow up for cancer with conventional care.

Nurse-led follow-up for cancer and other models are increasingly being used to reduce workload for outpatient clinics. This article reports the results of a recently published systematic review, which compared nurse-led follow up with conventional doctor-led followup. The implications for practice are highlighted, and recommendations for further research are made.

Follow-up of cancer in primary care versus secondary care: systematic review.

BACKGROUND: Cancer follow-up has traditionally been undertaken in secondary care, but there are increasing calls to deliver it in primary care. AIM: To compare the effectiveness and cost-effectiveness of primary versus secondary care follow-up of cancer patients, determine the effectiveness of the integration of primary care in routine hospital follow-up, and evaluate the impact of patient-initiated follow-up on primary care. DESIGN OF STUDY: Systematic review. SETTING: Primary and secondary care settings. METHOD: A search was carried out of 19 electronic databases, online trial registries, conference proceedings, and bibliographies of included studies. The review included comparative studies or economic evaluations of primary versus secondary care follow-up, hospital follow-up with formal primary care involvement versus conventional hospital follow-up, and hospital follow-up versus patient-initiated or minimal follow-up if the study reported the impact on primary care. RESULTS: There was no statistically significant difference for patient wellbeing, recurrence rate, survival, recurrence-related serious clinical events, diagnostic delay, or patient satisfaction. GP-led breast cancer follow-up was cheaper than hospital follow-up. Intensified primary health care resulted in increased home-care nurse contact, and improved discharge summary led to increased GP contact. Evaluation of patient-initiated or minimal follow-up found no statistically significant impact on the number of GP consultations or cancer-related referrals. CONCLUSION: Weak evidence suggests that breast cancer follow-up in primary care is effective. Interventions improving communication between primary and secondary care could lead to greater GP involvement. Discontinuation of formal follow-up may not increase GP workload. However, the quality of the data in general was poor, and no firm conclusions can be reached.

Patients' and healthcare professionals' views of cancer follow-up: systematic review.

BACKGROUND: Cancer follow-up places a significant burden on hospital outpatient clinics. There are increasing calls to develop alternative models of provision. AIM: To undertake a systematic review of qualitative studies examining patients' and healthcare professionals' views about cancer follow-up. DESIGN OF STUDY: Systematic review. SETTING: Primary and secondary care. METHOD: Comprehensive literature searches included: 19 electronic databases, online trial registries, conference proceedings, and bibliographies of included studies. Eligible studies included qualitative studies examining patients' and healthcare professionals' views of cancer follow-up. Studies of patients with any type of cancer, considered free of active disease, or no longer receiving active treatment were included. Findings were synthesised using thematic analysis. RESULTS: Nineteen studies were included; seven were linked to randomised controlled trials. Eight studies examined the views of healthcare professionals (four of which included GPs) and 16 examined the views of patients. Twelve descriptive themes were identified, from which 12 perceived implications for practice were derived. Most themes related to conventional follow-up in secondary care. Some views concerning other models of care were based on participants' ideas, rather than experiences. CONCLUSION: Patients' main concern is recurrent disease, and they find regular follow-up, expertise of specialists, and quick access to tests reassuring. Information regarding the effectiveness of follow-up is not given to patients who also have unmet information needs, which would help them to cope and be more involved. Continuity of care, unhurried consultations, and psychosocial support are important, but sometimes lacking in secondary care. GPs are thought to be unwilling and to have insufficient time and expertise to conduct follow-up.

Nurse-led vs. conventional physician-led follow-up for patients with cancer: systematic review.

AIM: This paper is a report of a systematic review of the effectiveness and cost-effectiveness of nurse-led follow-up for patients with cancer. BACKGROUND: As cancer survivorship increases, conventional follow-up puts a major burden on outpatient services. Nurse-led follow-up is a promising alternative. Data sources. Searches were conducted covering a period from inception to February 2007 of 19 electronic databases, seven online trial registries, five conference proceedings reference lists of previous reviews and included studies. REVIEW METHODS: Standard systematic review methodology was used. Comparative studies and economic evaluations of nurse-led vs. physician-led follow-up were eligible. Studies comparing different types of nurse-led follow-up were excluded. Any cancer was considered; any outcome measure included. RESULTS: Four randomised controlled trials were identified, two including cost analyses. There were no statistically significant differences in survival, recurrence or psychological morbidity. One study showed better HRQL measures for nurse-led follow-up, but one showed no difference, two showed a statistically significant difference for patient satisfaction, but two did not. Patients with lung cancer were more satisfied with nurse-led telephone follow-up and more were able to die at home. Patients with breast cancer thought patient-initiated follow-up convenient, but found conventional follow-up more reassuring. One study showed the cost of nurse-led follow-up to be less than that of physician-led follow-up, but no statistical comparison was made. CONCLUSION: Patients appeared satisfied with nurse-led follow-up. Patient-initiated or telephone follow-up could be practical alternatives to conventional care. However, well-conducted research is needed before equivalence to physician-led follow-up can be assured in terms of survival, recurrence, patient well-being and cost-effectiveness.

A survey of local health promotion initiatives for older people in Wales.

BACKGROUND: As the demographic profile of the UK changes, policy makers and practitioners have to respond to health challenges presented by a progressively ageing population. The health promotion plan for older people, aged over 50 years, in Wales included eight key areas: physical activity, healthy eating, home safety and warmth, emotional health, health protection, smoking, alcohol and sexual health. The aim of this study was to describe the extent, content and regional variation of existing health promotion initiatives for older people in Wales, provided by statutory, voluntary and private sector agencies. METHOD: A questionnaire was sent to senior health promotion specialists employed in the 22 local authority areas in Wales to ascertain details of all projects promoting health and wellbeing in the eight key areas where the priority population was aged over 50, or the majority of users were older people. Additional information was sought from project leads and websites. RESULTS: Eighteen questionnaires were returned; not all were fully completed. Four areas did not return a questionnaire. Additional information was obtained from internet searches but this mainly concerned national initiatives rather than local projects. In all, 120 projects were included, 11 were throughout Wales. Best provision was for physical activity, with 3 national and 42 local initiatives, but local provision was patchy. Healthy eating, and home safety and warmth had far fewer initiatives, as did health protection, which comprised two national immunisation campaigns. Smoking and alcohol misuse were poorly provided for, and there was no provision for older people's sexual health. Evaluation arrangements were poorly described. Half of those who responded identified unmet training needs. CONCLUSION: The reasons for patchy provision of services were not clear. Increased efforts to improve the coverage of interventions known to be effective should be made. Rigorous evaluation of projects is needed to ascertain the most effective and appropriate interventions, especially for alcohol misuse and sexual health. These conclusions are relevant to the other countries of the United Kingdom (UK), and more widely across Europe.

Improving response rates using a monetary incentive for patient completion of questionnaires: an observational study.

BACKGROUND: Poor response rates to postal questionnaires can introduce bias and reduce the statistical power of a study. To improve response rates in our trial in primary care we tested the effect of introducing an unconditional direct payment of 5 pounds for the completion of postal questionnaires. METHODS: We recruited patients in general practice with knee problems from sites across the United Kingdom. An evidence-based strategy was used to follow-up patients at twelve months with postal questionnaires. This included an unconditional direct payment of 5 pounds to patients for the completion and return of questionnaires. The first 105 patients did not receive the 5 pounds incentive, but the subsequent 442 patients did. We used logistic regression to analyse the effect of introducing a monetary incentive to increase the response to postal questionnaires. RESULTS: The response rate following reminders for the historical controls was 78.1% (82 of 105) compared with 88.0% (389 of 442) for those patients who received the 5 pounds payment (diff = 9.9%, 95% CI 2.3% to 19.1%). Direct payments significantly increased the odds of response (adjusted odds ratio = 2.2, 95% CI 1.2 to 4.0, P = 0.009) with only 12 of 442 patients declining the payment. The incentive did not save costs to the trial--the extra cost per additional respondent was almost 50 pounds. CONCLUSION: The direct payment of 5 pounds significantly increased the completion of postal questionnaires at negligible increase in cost for an adequately powered study.