Sadia Nafees

The Aarhus statement: improving design and reporting of studies on early cancer diagnosis

Early diagnosis is a key factor in improving the outcomes of cancer patients. A greater understanding of the pre-diagnostic patient pathways is vital yet, at present, research in this field lacks consistent definitions and methods. As a consequence much early diagnosis research is difficult to interpret. A consensus group was formed with the aim of producing guidance and a checklist for early cancer-diagnosis researchers. A consensus conference approach combined with nominal group techniques was used. The work was supported by a systematic review of early diagnosis literature, focussing on existing instruments used to measure time points and intervals in early cancer-diagnosis research. A series of recommendations for definitions and methodological approaches is presented. This is complemented by a checklist that early diagnosis researchers can use when designing and conducting studies in this field. The Aarhus checklist is a resource for early cancer-diagnosis research that should promote greater precision and transparency in both definitions and methods. Further work will examine whether the checklist can be readily adopted by researchers, and feedback on the guidance will be used in future updates.

The clinical effectiveness and cost-effectiveness of management strategies for sciatica: systematic review and economic model.

Background Sciatica is a symptom characterised by well-localised leg pain with a sharp, shooting or burning quality that radiates down the back of the leg and normally to the foot or ankle. It is often associated with numbness or altered sensation in the leg. Objectives To determine the clinical effectiveness and cost-effectiveness of different management strategies for sciatica. Data sources Major electronic databases (e.g. MEDLINE, EMBASE and NHS Economic Evaluation Database) and several internet sites including trial registries were searched up to December 2009. Review methods Systematic reviews were undertaken of the clinical effectiveness and cost-effectiveness of different treatment strategies for sciatica. Effectiveness data were synthesised using both conventional meta-analyses and mixed treatment comparison (MTC) methods. An economic model was then developed to estimate costs per quality-adjusted life-year gained for each treatment strategy. Results The searches identified 33,590 references, of which 270 studies met the inclusion criteria and 12 included a full economic evaluation. A further 42 ongoing studies and 93 publications that could not be translated were identified. The interventions were grouped into 18 treatment categories. A larger number of studies evaluated invasive interventions and non-opioids than other non-invasive interventions. The proportion of good-quality studies for each treatment category ranged from 0% to 50%. Compared with studies of less invasive interventions, studies of invasive treatments were more likely to confirm disc herniation by imaging, to limit patients included to those with acute sciatica (< 3 months’ duration) and to include patients who had received previous treatment. The MTC analyses gave an indication of relative therapeutic effect. The statistically significant odds ratios of global effect compared with inactive control were as follows: disc surgery 2.8, epidural injection 3.1, chemonucleolysis 2.0 and non-opioids 2.6. Disc surgery and epidural injections were associated with more adverse effects than the inactive control. There was some evidence for the effectiveness of biological agents and acupuncture. Opioid medication and activity restriction were found to be less effective than the comparator interventions and opioids were associated with more adverse effects than the inactive control. The full economic evaluations were of reasonable to good quality, but were not able to fully address our research question. Although individual studies raised a number of important issues, it was difficult to draw meaningful conclusions across studies because of their heterogeneity. The economic model demonstrated that stepped-care approaches to patient management were likely to be cost-effective, relative to strategies that involved direct referral to disc surgery. Limitations The limited number of studies for some comparisons, the high level of heterogeneity (within treatment comparisons) and the potential inconsistency (between treatment comparisons) weaken the interpretation of the MTC analyses. Conclusions These findings provide support for the effectiveness of currently used therapies for sciatica such as non-opioid medication, epidural corticosteroid injections and disc surgery, but also for chemonucleolysis, which is no longer used in the UK NHS. These findings do not provide support for the effectiveness of opioid analgesia, which is widely used in this patient group, or activity restriction. They also suggest that less frequently used treatments, such as acupuncture, and experimental treatments, such as anti-inflammatory biological agents, may be effective. Stepped-care approaches to treatment for patients with sciatica are cost-effective relative to direct referral for surgery. Future research should include randomised controlled trials with concurrent economic evaluation of biological agents and acupuncture compared with placebo or with currently used treatments. Development of alternative economic modelling approaches to assess relative cost-effectiveness of treatment regimes, based on the above trial data, would also be beneficial. Funding The National Institute for Health Research Health Technology Assessment programme.

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.

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

BackgroundThe 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.MethodsIn 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.ResultsAfter 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%).ConclusionsWe 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.Trial registrationISRCTN04475865

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

Summary A model‐based economic evaluation demonstrates that stepped approaches based on initial treatment with nonopioids are most likely to represent the most cost‐effective regimens for sciatica. ABSTRACT 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.

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.

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 ‘fast 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 ‘shock 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.

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.