Richard D Neal

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.

Variation in number of general practitioner consultations before hospital referral for cancer: findings from the 2010 National Cancer Patient Experience Survey in England

BACKGROUND Information from patient surveys can help to identify patient groups and cancers with the greatest potential for improvement in the experience and timeliness of cancer diagnosis. We aimed to examine variation in the number of pre-referral consultations with a general practitioner between patients with different cancers and sociodemographic characteristics. METHODS We analysed data from 41,299 patients with 24 different cancers who took part in the 2010 National Cancer Patient Experience Survey in England. We examined variation in the number of general practitioner consultations with cancer symptoms before hospital referral to diagnose cancer. Logistic regression was used to identify independent predictors of three or more pre-referral consultations, adjusting for cancer type, age, sex, deprivation quintile, and ethnic group. FINDINGS We identified wide variation between cancer types in the proportion of patients who had visited their general practitioner three or more times before hospital referral (7·4% [625 of 8408] for breast cancer and 10·1% [113 of 1124] for melanoma; 41·3% [193 of 467] for pancreatic cancer and 50·6% [939 of 1854] for multiple myeloma). In multivariable analysis, with patients with rectal cancer as the reference group, those with subsequent diagnosis of multiple myeloma (odds ratio [OR] 3·42, 95% CI 3·01-3·90), pancreatic cancer (2·35, 1·91-2·88), stomach cancer (1·96, 1·65-2·34), and lung cancer (1·68, 1·48-1·90) were more likely to have had three or more pre-referral consultations; conversely patients with subsequent diagnosis of breast cancer (0·19; 0·17-0·22), melanoma (0·34, 0·27-0·43), testicular cancer (0·47, 0·33-0·67), and endometrial cancer (0·59, 0·49-0·71) were more likely to have been referred to hospital after only one or two consultations. The probability of three or more pre-referral consultations was greater in young patients (OR for patients aged 16-24 years vs 65-74 years 2·12, 95% CI 1·63-2·75; p<0·0001), those from ethnic minorities (OR for Asian vs white 1·73, 1·45-2·08; p<0·0001; OR for black vs white 1·83, 1·51-2·23; p<0·0001), and women (OR for women vs men 1·28, 1·21-1·36; p<0·0001). We identified strong evidence of interactions between cancer type and age group and sex (p<0·0001 for both), and between age and ethnicity (p=0·0013). The model including these interactions showed a particularly strong sex effect for bladder cancer (OR for women vs men 2·31, 95% CI 1·98-2·69) and no apparent ethnic group differences in young patients aged 16-24 years, whilst the only cancers without an apparent age gradient were testicular cancer and mesothelioma. INTERPRETATION Our findings could help to prioritise and stratify early diagnosis initiatives and research, focusing on patients with cancers and sociodemographic characteristics with the largest potential for improvement. FUNDING None.

Evidence based general practice: a retrospective study of interventions in one training practice

Abstract Objectives: To estimate the proportion of interventions in general practice that are based on evidence from clinical trials and to assess the appropriateness of such an evaluation. Design: Retrospective review of case notes. Setting: One suburban training general practice. Subjects: 122 consecutive doctor-patient consultations over two days. Main outcome measures: Proportions of interventions based on randomised controlled trials (from literature search with Medline, pharmaceutical databases, and standard textbooks), on convincing non-experimental evidence, and without substantial evidence. Results: 21 of the 122 consultations recorded were excluded due to insufficient data; 31 of the interventions were based on randomised controlled trial evidence and 51 based on convincing non-experimental evidence. Hence 82/101 (81%) of interventions were based on evidence meeting our criteria. Conclusions: Most interventions within general practice are based on evidence from clinical trials, but the methods used in such trials may not be the most appropriate to apply to this setting. Key messages Key messages 81% of general practice can be described as evidence based using this method of assessment Evidence derived from different methodologies may be important for the assessment of the evidence base of general practice

Delays in the diagnosis of six cancers: analysis of data from the National Survey of NHS Patients: Cancer

The aim of this paper is to describe and compare components of diagnostic delay (patient, primary care, referral, secondary care) for six cancers (breast, colorectal, lung, ovarian, prostate and non-Hodgkins lymphoma), and to compare delays in patients who saw their GP prior to diagnosis with those who did not. Secondary data analysis of The National Survey of NHS Patients: Cancer was undertaken (65 192 patients). Breast cancer patients experienced the shortest total delays (mean 55.2 days), followed by lung (88.5), ovarian (90.3), non-Hodgkins lymphoma (102.8), colorectal (125.7) and prostate (148.5). Trends were similar for all components of delay. Compared with patient and primary care delays, referral delays and secondary care delays were much shorter. Patients who saw their GP prior to diagnosis experienced considerably longer total diagnostic delays than those who did not. There were significant differences in all components of delay between the six cancers. Reducing diagnostic delays with the intention of increasing the proportion of early stage cancers may improve cancer survival in the UK, which is poorer than most other European countries. Interventions aimed at reducing patient and primary care delays need to be developed and their effect on diagnostic stage and psychological distress evaluated.

Sociodemographic factors and delays in the diagnosis of six cancers: analysis of data from the ‘ National Survey of NHS Patients: Cancer ’

This paper aims to explore the relationship between sociodemographic factors and the components of diagnostic delay (total, patient and primary care, referral, secondary care) for these six cancers (breast, colorectal, lung, ovarian, prostate, or non-Hodgkins lymphoma). Secondary analysis of patient-reported data from the ‘National Survey of NHS patients: Cancer’ was undertaken (65 192 patients). Data were analysed using univariate analysis and Generalised Linear Modelling. With regard to total delay, the findings from the GLM showed that for colorectal cancer, the significant factors were marital status and age, for lung and ovarian cancer none of the factors were significant, for prostate cancer the only significant factor was social class, for non-Hodgkins lymphoma the only significant factor was age, and for breast cancer the significant factors were marital status and ethnic group. Where associations between any of the component delays were found, the direction of the association was always in the same direction (female subjects had longer delays than male subjects, younger people had longer delays than older people, single and separated/divorced people had longer delays than married people, lower social class groups had longer delays than higher social class groups, and Black and south Asian people had longer delays than white people). These findings should influence the design of interventions aimed at reducing diagnostic delays with the aim of improving morbidity, mortality, and psychological outcomes through earlier stage diagnosis.

Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes? Systematic review

Background:It is unclear whether more timely cancer diagnosis brings favourable outcomes, with much of the previous evidence, in some cancers, being equivocal. We set out to determine whether there is an association between time to diagnosis, treatment and clinical outcomes, across all cancers for symptomatic presentations.Methods:Systematic review of the literature and narrative synthesis.Results:We included 177 articles reporting 209 studies. These studies varied in study design, the time intervals assessed and the outcomes reported. Study quality was variable, with a small number of higher-quality studies. Heterogeneity precluded definitive findings. The cancers with more reports of an association between shorter times to diagnosis and more favourable outcomes were breast, colorectal, head and neck, testicular and melanoma.Conclusions:This is the first review encompassing many cancer types, and we have demonstrated those cancers in which more evidence of an association between shorter times to diagnosis and more favourable outcomes exists, and where it is lacking. We believe that it is reasonable to assume that efforts to expedite the diagnosis of symptomatic cancer are likely to have benefits for patients in terms of improved survival, earlier-stage diagnosis and improved quality of life, although these benefits vary between cancers.

The diagnostic value of symptoms for colorectal cancer in primary care: a systematic review

BACKGROUND Over 37,000 new colorectal cancers are diagnosed in the UK each year. Most present symptomatically to primary care. AIM To conduct a systematic review of the diagnostic value of symptoms associated with colorectal cancer. DESIGN Systematic review. METHOD MEDLINE, Embase, Cochrane Library, and CINAHL were searched to February 2010, for diagnostic studies of symptomatic adult patients in primary care. Studies of asymptomatic patients, screening, referred populations, or patients with colorectal cancer recurrences, or with fewer than 100 participants were excluded. The target condition was colorectal cancer. Data were extracted to estimate the diagnostic performance of each symptom or pair of symptoms. Data were pooled in a meta-analysis. The quality of studies was assessed with the QUADAS tool. RESULTS Twenty-three studies were included. Positive predictive values (PPVs) for rectal bleeding from 13 papers ranged from 2.2% to 16%, with a pooled estimate of 8.1% (95% confidence interval [CI] = 6.0% to 11%) in those aged ≥ 50 years. Pooled PPV estimates for other symptoms were: abdominal pain (three studies) 3.3% (95% CI = 0.7% to 16%); and anaemia (four studies) 9.7% (95% CI = 3.5% to 27%). For rectal bleeding accompanied by weight loss or change in bowel habit, pooled positive likelihood ratios (PLRs) were 1.9 (95% CI = 1.3 to 2.8) and 1.8 (95% CI = 1.3 to 2.5) respectively, suggesting higher risk when both symptoms were present. Conversely, the PLR was one or less for abdominal pain, diarrhoea, or constipation accompanying rectal bleeding. CONCLUSION The findings suggest that investigation of rectal bleeding or anaemia in primary care patients is warranted, irrespective of whether other symptoms are present. The risks from other single symptoms are lower, though multiple symptoms also warrant investigation.

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.

The expanding role of primary care in cancer control

The nature of cancer control is changing, with an increasing emphasis, fuelled by public and political demand, on prevention, early diagnosis, and patient experience during and after treatment. At the same time, primary care is increasingly promoted, by governments and health funders worldwide, as the preferred setting for most health care for reasons of increasing need, to stabilise health-care costs, and to accommodate patient preference for care close to home. It is timely, then, to consider how this expanding role for primary care can work for cancer control, which has long been dominated by highly technical interventions centred on treatment, and in which the contribution of primary care has been largely perceived as marginal. In this Commission, expert opinion from primary care and public health professionals with academic and clinical cancer expertise—from epidemiologists, psychologists, policy makers, and cancer specialists—has contributed to a detailed consideration of the evidence for cancer control provided in primary care and community care settings. Ranging from primary prevention to end-of-life care, the scope for new models of care is explored, and the actions needed to effect change are outlined. The strengths of primary care—its continuous, coordinated, and comprehensive care for individuals and families—are particularly evident in prevention and diagnosis, in shared follow-up and survivorship care, and in end-of-life care. A strong theme of integration of care runs throughout, and its elements (clinical, vertical, and functional) and the tools needed for integrated working are described in detail. All of this change, as it evolves, will need to be underpinned by new research and by continuing and shared multiprofessional development.

Do diagnostic delays in cancer matter

Background:The United Kingdom has poorer cancer outcomes than many other countries due partly to delays in diagnosing symptomatic cancer, leading to more advanced stage at diagnosis. Delays can occur at the level of patients, primary care, systems and secondary care. There is considerable potential for interventions to minimise delays and lead to earlier-stage diagnosis.Methods:Scoping review of the published studies, with a focus on methodological issues.Results:Trial data in this area are lacking and observational studies often show no association or negative ones. This review offers methodological explanations for these counter-intuitive findings.Conclusion:While diagnostic delays do matter, their importance is uncertain and must be determined through more sophisticated methods.