Predictive accuracy of risk prediction models for recurrence, metastasis and survival for early-stage cutaneous melanoma: a systematic review.

OBJECTIVES: To identify prognostic models for melanoma survival, recurrence and metastasis among American Joint Committee on Cancer stage I and II patients postsurgery; and evaluate model performance, including overall survival (OS) prediction. DESIGN: Systematic review and narrative synthesis. DATA SOURCES: Searched MEDLINE, Embase, CINAHL, Cochrane Library, Science Citation Index and grey literature sources including cancer and guideline websites from 2000 to September 2021. ELIGIBILITY CRITERIA: Included studies on risk prediction models for stage I and II melanoma in adults ≥18 years. Outcomes included OS, recurrence, metastases and model performance. No language or country of publication restrictions were applied. DATA EXTRACTION AND SYNTHESIS: Two pairs of reviewers independently screened studies, extracted data and assessed the risk of bias using the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies checklist and the Prediction study Risk of Bias Assessment Tool. Heterogeneous predictors prevented statistical synthesis. RESULTS: From 28 967 records, 15 studies reporting 20 models were included; 8 (stage I), 2 (stage II), 7 (stages I-II) and 7 (stages not reported), but were clearly applicable to early stages. Clinicopathological predictors per model ranged from 3-10. The most common were: ulceration, Breslow thickness/depth, sociodemographic status and site. Where reported, discriminatory values were ≥0.7. Calibration measures showed good matches between predicted and observed rates. None of the studies assessed clinical usefulness of the models. Risk of bias was high in eight models, unclear in nine and low in three. Seven models were internally and externally cross-validated, six models were externally validated and eight models were internally validated. CONCLUSIONS: All models are effective in their predictive performance, however the low quality of the evidence raises concern as to whether current follow-up recommendations following surgical treatment is adequate. Future models should incorporate biomarkers for improved accuracy. PROSPERO REGISTRATION NUMBER: CRD42018086784.

Optimal surveillance strategies for patients with stage 1 cutaneous melanoma post primary tumour excision: three systematic reviews and an economic model.

BACKGROUND: Malignant melanoma is the fifth most common cancer in the UK, with rates continuing to rise, resulting in considerable burden to patients and the NHS. OBJECTIVES: The objectives were to evaluate the effectiveness and cost-effectiveness of current and alternative follow-up strategies for stage IA and IB melanoma. REVIEW METHODS: Three systematic reviews were conducted. (1) The effectiveness of surveillance strategies. Outcomes were detection of new primaries, recurrences, metastases and survival. Risk of bias was assessed using the Cochrane Collaboration's Risk-of-Bias 2.0 tool. (2) Prediction models to stratify by risk of recurrence, metastases and survival. Model performance was assessed by study-reported measures of discrimination (e.g. D-statistic, Harrel's c-statistic), calibration (e.g. the Hosmer-Lemeshow 'goodness-of-fit' test) or overall performance (e.g. Brier score, R2). Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). (3) Diagnostic test accuracy of fine-needle biopsy and ultrasonography. Outcomes were detection of new primaries, recurrences, metastases and overall survival. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Review data and data from elsewhere were used to model the cost-effectiveness of alternative surveillance strategies and the value of further research. RESULTS: (1) The surveillance review included one randomised controlled trial. There was no evidence of a difference in new primary or recurrence detected (risk ratio 0.75, 95% confidence interval 0.43 to 1.31). Risk of bias was considered to be of some concern. Certainty of the evidence was low. (2) Eleven risk prediction models were identified. Discrimination measures were reported for six models, with the area under the operating curve ranging from 0.59 to 0.88. Three models reported calibration measures, with coefficients of ≥ 0.88. Overall performance was reported by two models. In one, the Brier score was slightly better than the American Joint Committee on Cancer scheme score. The other reported an R2 of 0.47 (95% confidence interval 0.45 to 0.49). All studies were judged to have a high risk of bias. (3) The diagnostic test accuracy review identified two studies. One study considered fine-needle biopsy and the other considered ultrasonography. The sensitivity and specificity for fine-needle biopsy were 0.94 (95% confidence interval 0.90 to 0.97) and 0.95 (95% confidence interval 0.90 to 0.97), respectively. For ultrasonography, sensitivity and specificity were 1.00 (95% confidence interval 0.03 to 1.00) and 0.99 (95% confidence interval 0.96 to 0.99), respectively. For the reference standards and flow and timing domains, the risk of bias was rated as being high for both studies. The cost-effectiveness results suggest that, over a lifetime, less intensive surveillance than recommended by the National Institute for Health and Care Excellence might be worthwhile. There was considerable uncertainty. Improving the diagnostic performance of cancer nurse specialists and introducing a risk prediction tool could be promising. Further research on transition probabilities between different stages of melanoma and on improving diagnostic accuracy would be of most value. LIMITATIONS: Overall, few data of limited quality were available, and these related to earlier versions of the American Joint Committee on Cancer staging. Consequently, there was considerable uncertainty in the economic evaluation. CONCLUSIONS: Despite adoption of rigorous methods, too few data are available to justify changes to the National Institute for Health and Care Excellence recommendations on surveillance. However, alternative strategies warrant further research, specifically on improving estimates of incidence, progression of recurrent disease; diagnostic accuracy and health-related quality of life; developing and evaluating risk stratification tools; and understanding patient preferences. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018086784. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol 25, No. 64. See the NIHR Journals Library website for further project information.

Malignant melanoma is the deadliest of skin cancers; in the UK, > 2500 people die from it every year. Initially, the cancer is removed surgically, which cures it for most people, but, for some, the cancer returns. For this reason, after a melanoma is removed, patients are followed up to see if the melanoma reoccurs or if new melanomas have developed. It is felt that early cancer detection improves the chance of future treatment working. A key question is how best to follow up patients after initial melanoma surgery. This study concentrates on the earliest stage of melanoma (American Joint Committee on Cancer stage I), which accounts for more than 7 out of 10 of all melanoma diagnoses. The study also investigates if new ways of follow-up could be at least as good as current practice and a better use of NHS money. We systematically reviewed studies comparing different ways of organising follow-up, and then methods to identify those patients at high risk of developing a further melanoma and how good different tests are at detecting this cancer. We then compared different possible follow-up strategies. For each strategy, we considered its impact on quality and length of life, and how well it used NHS resources. We found little evidence to support a change in how follow-up should be organised currently. There were some ways of organising follow-up that might be better than current care, but further research is needed. We found that new research on whether or not follow-up should be performed by a cancer nurse specialist, rather than a dermatologist or surgeon, would be worthwhile. We also found that more research could be worthwhile on how frequently melanoma recurs and spreads, as well as how accurately a diagnosis of further cancer is made and how to identify those most at risk of further melanoma spread.

Axillary treatment for operable primary breast cancer.

BACKGROUND: Axillary surgery is an established part of the management of primary breast cancer. It provides staging information to guide adjuvant therapy and potentially local control of axillary disease. Several alternative approaches to axillary surgery are available, most of which aim to spare a proportion of women the morbidity of complete axillary dissection. OBJECTIVES: To assess the benefits and harms of alternative approaches to axillary surgery (including omitting such surgery altogether) in terms of overall survival; local, regional and distant recurrences; and adverse events. SEARCH METHODS: We searched the Cochrane Breast Cancer Group Specialised Register, MEDLINE, Pre-MEDLINE, Embase, CENTRAL, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov on 12 March 2015 without language restrictions. We also contacted study authors and checked reference lists. SELECTION CRITERIA: Randomised controlled trials (RCTs) including women with clinically defined operable primary breast cancer conducted to compare axillary lymph node dissection (ALND) with no axillary surgery, axillary sampling or sentinel lymph node biopsy (SLNB); RCTs comparing axillary sampling with SLNB or no axillary surgery; RCTs comparing SLNB with no axillary surgery; and RCTs comparing ALND with or without radiotherapy (RT) versus RT alone. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed each potentially relevant trial for inclusion. We independently extracted outcome data, risk of bias information and study characteristics from all included trials. We pooled data according to trial interventions, and we used hazard ratios (HRs) for time-to-event outcomes and odds ratios (OR) for binary outcomes. MAIN RESULTS: We included 26 RCTs in this review. Studies were at low or unclear risk of selection bias. Blinding was not done, but this was only considered a source of bias for outcomes with potential for subjectivity in measurements. We found no RCTs of axillary sampling versus SLNB, axillary sampling versus no axillary surgery or SLNB versus no axillary surgery. No axillary surgery versus ALND Ten trials involving 3849 participants compared no axillary surgery versus ALND. Moderate quality evidence showed no important differences between overall survival of women in the two groups (HR 1.06, 95% confidence interval (CI) 0.96 to 1.17; 3849 participants; 10 studies) although no axillary surgery increased the risk of locoregional recurrence (HR ranging from 1.10 to 3.06; 20,863 person-years of follow-up; four studies). It was uncertain whether no surgery increased the risk of distant metastasis compared with ALND (HR 1.06, 95% CI 0.87 to 1.30; 946 participants; two studies). Low-quality evidence indicated no axillary surgery decreased the risk of lymphoedema compared with ALND (OR 0.31, 95% CI 0.23 to 0.43; 1714 participants; four studies). Axillary sampling versus ALND Six trials involving 1559 participants compared axillary sampling versus ALND. Low-quality evidence indicated similar effectiveness of axillary sampling compared with ALND in terms of overall survival (HR 0.94, 95% CI 0.73 to 1.21; 967 participants; three studies) but it was unclear whether axillary sampling led to increased risk of local recurrence compared with ALND (HR 1.41, 95% CI 0.94 to 2.12; 1404 participants; three studies). The relative effectiveness of axillary sampling and ALND for locoregional recurrence (HR 0.74, 95% CI 0.46 to 1.20; 406 participants; one study) and distant metastasis was uncertain (HR 1.05, 95% CI 0.74 to 1.49; 406 participants; one study). Lymphoedema was less likely after axillary sampling than after ALND (OR 0.32, 95% CI 0.13 to 0.81; 80 participants; one study). SLNB versus ALND Seven trials involving 9426 participants compared SLNB with ALND. Moderate-quality evidence showed similar overall survival following SLNB compared with ALND (HR 1.05, 95% CI 0.89 to 1.25; 6352 participants; three studies; moderate-quality evidence). Differences in local recurrence (HR 0.94, 95% CI 0.24 to 3.77; 516 participants; one study), locoregional recurrence (HR 0.96, 95% CI 0.74 to 1.24; 5611 participants; one study) and distant metastasis (HR 0.80, 95% CI 0.42 to 1.53; 516 participants; one study) were uncertain. However, studies showed little absolute difference in the aforementioned outcomes. Lymphoedema was less likely after SLNB than ALND (OR ranged from 0.04 to 0.60; three studies; 1965 participants; low-quality evidence). Three studies including 1755 participants reported quality of life: Investigators in two studies found quality of life better after SLNB than ALND, and in the other study observed no difference. RT versus ALND Four trials involving 2585 participants compared RT alone with ALND (with or without RT). High-quality evidence indicated that overall survival was reduced among women treated with radiotherapy alone compared with those treated with ALND (HR 1.10, 95% CI 1.00 to 1.21; 2469 participants; four studies), and local recurrence was less likely in women treated with radiotherapy than in those treated with ALND (HR 0.80, 95% CI 0.64 to 0.99; 22,256 person-years of follow-up; four studies). Risk of distant metastasis was similar for radiotherapy alone as for ALND (HR 1.07, 95% CI 0.93 to 1.25; 1313 participants; one study), and whether lymphoedema was less likely after RT alone than ALND remained uncertain (OR 0.47, 95% CI 0.16 to 1.44; 200 participants; one study). Less surgery versus ALND When combining results from all trials, treatment involving less surgery was associated with reduced overall survival compared with ALND (HR 1.08, 95% CI 1.01 to 1.17; 6478 participants; 18 studies). Whether local recurrence was reduced with less axillary surgery when compared with ALND was uncertain (HR 0.90, 95% CI 0.75 to 1.09; 24,176 participant-years of follow up; eight studies). Locoregional recurrence was more likely with less surgery than with ALND (HR 1.53, 95% CI 1.31 to 1.78; 26,880 participant-years of follow-up; seven studies). Whether risk of distant metastasis was increased after less axillary surgery compared with ALND was uncertain (HR 1.07, 95% CI 0.95 to 1.20; 2665 participants; five studies). Lymphoedema was less likely after less axillary surgery than with ALND (OR 0.37, 95% CI 0.29 to 0.46; 3964 participants; nine studies).No studies reported on disease control in the axilla. AUTHORS' CONCLUSIONS: This review confirms the benefit of SLNB and axillary sampling as alternatives to ALND for axillary staging, supporting the view that ALND of the clinically and radiologically uninvolved axilla is no longer acceptable practice in people with breast cancer.

Diagnostic value of symptoms of oesophagogastric cancers in primary care: a systematic review and meta-analysis.

BACKGROUND: Selection of primary care patients for investigation of potential oesophagogastric cancer is difficult, as the symptoms may represent benign conditions, which are also more common. AIM: To review systematically the presenting features of oesophagogastric cancers in primary care, including open-access endoscopy clinics. DESIGN AND SETTING: Systematic review and meta-analysis. METHOD: MEDLINE®, Embase, the Cochrane Library, and CINAHL were searched for studies of adults who were symptomatic and presented in primary care or open-access endoscopy clinics. Exclusions were being asymptomatic, screening, or recurrent cancers. Data were extracted to estimate the diagnostic performance of features of oesophagogastric cancers and summarised in a meta-analysis. RESULTS: Fourteen studies were identified. The strongest summary sensitivity and specificity estimates were for: dyspepsia 0.42 (95% confidence interval [CI] 0.29 to 0.56) and 0.48 (95% CI = 0.31 to 0.65); pain 0.41 (95% CI = 0.24 to 0.62) and 0.75 (95% CI = 0.51 to 0.89); and dysphagia 0.32 (95% CI = 0.17 to 0.52) and 0.92 (95% CI = 0.81 to 0.97). Summary positive likelihood ratios (LR+) and diagnostic odds ratios were: dyspepsia 0.79 (95% CI = 0.55 to 1.15) and 0.65 (95% CI = 0.32 to 1.33); pain 1.64 (95% CI = 1.20 to 2.24) and 2.09 (95% CI = 1.57 to 2.77); and dysphagia 4.32 (95% CI = 2.46 to 7.58) and 5.91 (95% CI = 3.56 to 9.82). Sensitivity was lower for: anaemia 0.12 [95% Cl = 0.08 to 0.19] with specificity 0.97 [95% Cl = 0.94 to 0.99]; nausea/vomiting/bloating 0.17 [95% Cl = 0.05 to 0.46] and 0.84 [95% Cl = 0.60 to 0.94] respectively; reflux 0.23 [95% Cl = 0.10 to 0.46] and 0.70 [95% Cl = 0.59 to 0.80]; weight loss 0.25 [95% Cl = 0.12 to 0.43] and 0.96 [95% Cl = 0.88 to 0.98]. [corrected]. Corresponding LR+ were: anaemia 4.32 (95% CI = 2.64 to 7.08); nausea/vomiting/bloating 1.07 (95% CI = 0.52 to 2.19); reflux 0.78 (95% CI = 0.47 to 1.78) and; weight loss 5.46 (95% CI = 3.47 to 8.60). CONCLUSION: Dysphagia, weight loss, and anaemia show the strongest association but with relatively low sensitivity and high specificity. The findings support the value of investigation of these symptoms, but also suggest that, in a population of patients who are low risk but not no-risk, investigation is not currently recommended.

The effectiveness of emergency obstetric referral interventions in developing country settings: a systematic review.

BACKGROUND: Pregnancy complications can be unpredictable and many women in developing countries cannot access health facilities where life-saving care is available. This study assesses the effects of referral interventions that enable pregnant women to reach health facilities during an emergency, after the decision to seek care is made. METHODS AND FINDINGS: Selected bibliographic databases were searched with no date or language restrictions. Randomised controlled trials and quasi experimental study designs with a comparison group were included. Outcomes of interest included maternal and neonatal mortality and other intermediate measures such as service utilisation. Two reviewers independently selected, appraised, and extracted articles using predefined fields. Forest plots, tables, and qualitative summaries of study quality, size, and direction of effect were used for analysis. Nineteen studies were included. In South Asian settings, four studies of organisational interventions in communities that generated funds for transport reduced neonatal deaths, with the largest effect seen in India (odds ratio 0·48 95% CI 0·34-0·68). Three quasi experimental studies from sub-Saharan Africa reported reductions in stillbirths with maternity waiting home interventions, with one statistically significant result (OR 0.56 95% CI 0.32-0.96). Effects of interventions on maternal mortality were unclear. Referral interventions usually improved utilisation of health services but the opposite effect was also documented. The effects of multiple interventions in the studies could not be disentangled. Explanatory mechanisms through which the interventions worked could not be ascertained. CONCLUSIONS: Community mobilisation interventions may reduce neonatal mortality but the contribution of referral components cannot be ascertained. The reduction in stillbirth rates resulting from maternity waiting homes needs further study. Referral interventions can have unexpected adverse effects. To inform the implementation of effective referral interventions, improved monitoring and evaluation practices are necessary, along with studies that develop better understanding of how interventions work.

Is MRI better than CT for detecting a vascular component to dementia? A systematic review and meta-analysis.

BACKGROUND: Identification of causes of dementia soon after symptom onset is important, because appropriate treatment of some causes of dementia can slow or halt its progression or enable symptomatic treatment where appropriate. The accuracy of MRI and CT, and whether MRI is superior to CT, in detecting a vascular component to dementia in autopsy confirmed and clinical cohorts of patients with VaD, combined AD and VaD ("mixed dementia"), and AD remain unclear. We conducted a systematic review and meta-analysis to investigate this question. METHODS: We searched eight databases and screened reference lists to identify studies addressing the review question. We assessed study quality using QUADAS. We estimated summary diagnostic accuracy according to imaging finding, and ratios of diagnostic odds ratios (RDORs) for MRI versus CT and high versus low risk of bias. RESULTS: We included 7 autopsy and 31 non-autopsy studies. There was little evidence that selective patient enrolment and risk of incorporation bias impacted on diagnostic accuracy (p = 0.12 to 0.95). The most widely reported imaging finding was white matter hyperintensities. For CT (11 studies) summary sensitivity and specificity were 71% (95% CI 53%-85%) and 55% (44%-66%). Corresponding figures for MRI (6 studies) were 95% (87%-98%) and 26% (12%-50%). General infarcts was the most specific imaging finding on MRI (96%; 95% CI 94%-97%) and CT (96%; 93%-98%). However, sensitivity was low for both MRI (53%; 36%-70%) and CT (52%; 22% to 80%). No imaging finding had consistently high sensitivity. Based on non-autopsy studies, MRI was more accurate than CT for six of seven imaging findings, but confidence intervals were wide. CONCLUSION: There is insufficient evidence to suggest that MRI is superior to CT with respect to identifying cerebrovascular changes in autopsy-confirmed and clinical cohorts of VaD, AD, and 'mixed dementia'.

Reporting of factorial trials of complex interventions in community settings: a systematic review.

BACKGROUND: Standards for the reporting of factorial randomised trials remain to be established. We aimed to review the quality of reporting of methodological aspects of published factorial trials of complex interventions in community settings. METHODS: We searched MEDLINE, EMBASE, PsychInfo and the Cochrane Controlled Trials Register to identify factorial randomised trials of complex interventions in community settings from January 2000 to August 2009. We also conducted a citation search of two review papers published in 2003. Data were extracted by two reviewers on 22 items relating to study design, analysis and presentation. RESULTS: We identified 5941 unique titles, from which 116 full papers were obtained and 76 were included in the review. The included trials reflected a broad range of target conditions and types of intervention. The median sample size was 400 (interquartile range 191-1001). Most (88%) trials employed a 2 × 2 factorial design. Few trials (21%) explicitly stated the rationale for using a factorial design. Reporting of aspects of design, analysis or presentation specific to factorial trials was variable, but there was no evidence that reporting of these aspects was different for trials published before or after 2003. However, for CONSORT items that apply generally to the reporting of all trials, there was some evidence that later studies were more likely to report employing an intention-to-treat (ITT) approach (78% vs 52%), present appropriate between-group estimates of effect (88% vs 63%), and present standard errors or 95% confidence intervals for such estimates (78% vs 56%). Interactions between interventions and some measure of the precision associated with such effects were reported in only 14 (18%) trials. CONCLUSIONS: Reports of factorial trials of complex interventions in community settings vary in the amount of information they provide regarding important methodological aspects of design and analysis. This variability supports the extension of CONSORT guidelines to include the specific reporting of factorial trials.

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.

Developing a sensitive search strategy in MEDLINE to retrieve studies on assessment of the diagnostic performance of imaging techniques.

PURPOSE: To prospectively develop a search strategy in MEDLINE for identifying studies on the diagnostic performance of any imaging modality, with maximized and minimized retrieval of relevant and irrelevant studies, respectively. MATERIALS AND METHODS: Predefined inclusion criteria were used to conduct a hand search of two sets of radiologic journal articles for studies on assessment of the diagnostic performance of imaging techniques. These two sets of articles formed independent derivation and validation record sets for developing and evaluating the search strategy. The sensitivity and positive predictive values (PPVs) of search terms from the derivation reference-standard set of records were used to select terms and develop two components of the search strategy. The first component was used to identify any study (from the imaging literature) in which diagnostic test performance was assessed. The second component was used to identify studies of any imaging modality. The two components were combined in the final search strategy. The sensitivity, specificity, and PPV of the search strategy in the derivation and validation record sets were calculated. RESULTS: The final search strategy had a sensitivity of 92.8%, a specificity of 58.5%, and a PPV of 25.1% for retrieval of the derivation set of records. Validation with an independent set of records gave a sensitivity of 91.9% (95% confidence interval [CI]: 87.1%, 95.1%), a specificity of 52.2% (95% CI: 49.2%, 55.2%), and a PPV of 25.1% (95% CI: 22.0%, 28.5%). Removal of irrelevant publication types further improved specificity and PPV in the validation set: to 77.6% (95% CI: 75.0%, 80.0%) and 40.9% (95% CI: 36.2%, 45.7%), respectively. The volume of imaging literature retrieved from MEDLINE by using the described search strategy has tripled since 1975. CONCLUSION: A sensitive search strategy to identify studies of the diagnostic performance of any imaging test was developed and validated. The retrieval estimates of this strategy in MEDLINE are adequate to develop a register of studies.

Factors associated with teenage pregnancy in the European Union countries: a systematic review.

BACKGROUND: As part of the REPROSTAT2 project, this systematic review aimed to identify factors associated with teenage pregnancy in 25 European Union countries. METHODS: The search strategy included electronic bibliographic databases (1995 to May 2005), bibliographies of selected articles and requests to all country representatives of the research team for relevant reports and publications. Primary outcome measure was conception. Inclusion criteria were quantitative studies of individual-level factors associated with teenage (13-19 years) pregnancy in EU countries. RESULTS: Of 4444 studies identified and screened, 20 met the inclusion criteria. Most of the included studies took place in UK and Nordic countries. The well-recognized factors of socioeconomic disadvantage, disrupted family structure and low educational level and aspiration appear consistently associated with teenage pregnancy. However, evidence that access to services in itself is a protective factor remains inconsistent. Although further associations with diverse risk-taking behaviours and lifestyle, sexual health knowledge, attitudes and behaviour are reported, the independent effects of these factors too remain unclear. CONCLUSIONS: Included studies varied widely in terms of methods and definitions used. This heterogeneity within the studies leaves two outstanding issues. First, we cannot synthesize or generalize key findings as to how all these factors interact with one another and which factors are the most significant. Second, it is not possible to examine potential variation between countries. Future research ensuring comparability and generalizability of results related to teenage sexual health outcomes will help gain insight into the international variation in observed pregnancy rates and better inform interventions.