An investigation of routes to cancer diagnosis in 10 international jurisdictions, as part of the International Cancer Benchmarking Partnership: survey development and implementation

Objectives This paper describes the methods used in the International Cancer Benchmarking Partnership Module 4 Survey (ICBPM4) which examines time intervals and routes to cancer diagnosis in 10 jurisdictions. We present the study design with defining and measuring time intervals, identifying patients with cancer, questionnaire development, data management and analyses.
Design and setting Recruitment of participants to the ICBPM4 survey is based on cancer registries in each jurisdiction. Questionnaires draw on previous instruments and have been through a process of cognitive testing and piloting in three jurisdictions followed by standardised translation and adaptation. Data analysis focuses on comparing differences in time intervals and routes to diagnosis in the jurisdictions.
Participants Our target is 200 patients with symptomatic breast, lung, colorectal and ovarian cancer in each jurisdiction. Patients are approached directly or via their primary care physician (PCP). Patients’ PCPs and cancer treatment specialists (CTSs) are surveyed, and ‘data rules’ are applied to combine and reconcile conflicting information. Where CTS information is unavailable, audit information is sought from treatment records and databases.
Main outcomes Reliability testing of the patient questionnaire showed that agreement was complete (κ=1) in four items and substantial (κ=0.8, 95% CI 0.333 to 1) in one item. The identification of eligible patients is sufficient to meet the targets for breast, lung and colorectal cancer. Initial patient and PCP survey response rates from the UK and Sweden are comparable with similar published surveys. Data collection was completed in early 2016 for all cancer types.
Conclusion An international questionnaire-based survey of patients with cancer, PCPs and CTSs has been developed and launched in 10 jurisdictions. ICBPM4 will help to further understand international differences in cancer survival by comparing time intervals and routes to cancer diagnosis.

Naming the pain in requirements engineering: Contemporary problems, causes, and effects in practice

Requirements Engineering (RE) has received much attention in research and practice due to its importance to software project success. Its inter-disciplinary nature, the dependency to the customer, and its inherent uncertainty still render the discipline diffcult to investigate. This results in a lack of empirical data. These are necessary, however, to demonstrate which practically relevant RE problems exist and to what extent they matter. Motivated by this situation, we initiated the Naming the Pain in Requirements Engineering (NaPiRE) initiative which constitutes a globally distributed, bi-yearly replicated family of surveys on the status quo and problems in practical RE.

In this article, we report on the analysis of data obtained from 228 companies in 10 countries. We apply Grounded Theory to the data obtained from NaPiRE and reveal which contemporary problems practitioners encounter. To this end, we analyse 21 problems derived from the literature with respect to their relevance and criticality in dependency to their context, and we complement this picture with a cause-effect analysis showing the causes and effects surrounding the most critical problems.

Our results give us a better understanding of which problems exist and how they manifest themselves in practical environments. Thus, we provide a rst step to ground contributions to RE on empirical observations which, by now, were dominated by conventional wisdom only.

Respecting and fulfilling the right of post-primary pupils to consent to participate in trials and evaluative research: A discussion paper

This paper provides an introduction to issues surrounding the participation rights of young people in research and the implications of their growing involvement in research as well as providing a discourse on the ethical implications related to consent. The unique contribution of this paper is that it considers children’s rights in respect to the increasing opportunities for young people to take part in evaluation research. The aim of this paper, therefore, is to acknowledge the growing involvement for young people in research and the implications of ensuring that their rights of participation are respected. Secondly we will consider the children’s rights legislation and our obligations as researchers to implement this. Finally we will explore consent as an issue in its own right as well as the practicalities of accessing participants. This paper will postulate that any research about young people should involve and prioritise at all stages of the research process; including participation in decision-making. We conclude by identifying five key principles, which we believe can help to facilitate the fulfilment of post-primary pupils’ ability to consent to participate in trials and evaluative research.

Variation in pre-PCR processing of FFPE samples leads to discrepancies in BRAF and EGFR mutation detection: a diagnostic RING trial.

AIMS: Mutation detection accuracy has been described extensively; however, it is surprising that pre-PCR processing of formalin-fixed paraffin-embedded (FFPE) samples has not been systematically assessed in clinical context. We designed a RING trial to (i) investigate pre-PCR variability, (ii) correlate pre-PCR variation with EGFR/BRAF mutation testing accuracy and (iii) investigate causes for observed variation. METHODS: 13 molecular pathology laboratories were recruited. 104 blinded FFPE curls including engineered FFPE curls, cell-negative FFPE curls and control FFPE tissue samples were distributed to participants for pre-PCR processing and mutation detection. Follow-up analysis was performed to assess sample purity, DNA integrity and DNA quantitation. RESULTS: Rate of mutation detection failure was 11.9%. Of these failures, 80% were attributed to pre-PCR error. Significant differences in DNA yields across all samples were seen using analysis of variance (p

Cost-effectiveness of zoledronic acid and strontium-89 as bone protecting treatments in addition to chemotherapy in patients with metastatic castrate-refractory prostate cancer: results from the TRAPEZE trial (ISRCTN 12808747)

OBJECTIVE: To evaluate the cost-effectiveness of adding zoledronic acid or strontium-89 to standard docetaxel chemotherapy for patients with castrate-refractory prostate cancer (CRPC).

PATIENTS AND METHODS: Data on resource use and quality of life for 707 patients collected prospectively in the TRAPEZE 2 × 2 factorial randomised trial (ISRCTN 12808747) were used to assess the cost-effectiveness of i) zoledronic acid versus no zoledronic acid (ZA vs. no ZA), and ii) strontium-89 versus no strontium-89 (Sr89 vs. no Sr89). Costs were estimated from the perspective of the National Health Service in the UK and included expenditures for trial treatments, concomitant medications, and use of related hospital and primary care services. Quality-adjusted life-years (QALYs) were calculated according to patients' responses to the generic EuroQol EQ-5D-3L instrument, which evaluates health status. Results are expressed as incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves.

RESULTS: The per-patient cost for ZA was £12 667, £251 higher than the equivalent cost in the no ZA group. Patients in the ZA group had on average 0.03 QALYs more than their counterparts in no ZA group. The ICER for this comparison was £8 005. Sr89 was associated with a cost of £13 230, £1365 higher than no Sr89, and a gain of 0.08 QALYs compared to no Sr89. The ICER for Sr89 was £16 884. The probabilities of ZA and Sr89 being cost-effective were 0.64 and 0.60, respectively.

CONCLUSIONS: The addition of bone-targeting treatments to standard chemotherapy led to a small improvement in QALYs for a modest increase in cost (or cost-savings). ZA and Sr89 resulted in ICERs below conventional willingness-to-pay per QALY thresholds, suggesting that their addition to chemotherapy may represent a cost-effective use of resources.

The EU Referendum and the UK Environment: An Expert Review:How has EU membership affected the UK and what might change in the event of a vote to Remain or Leave

This expert review provides a detailed review of the academic evidence on how EU membership has influenced UK policies, systems of decision making and environmental quality. Containing 14 chapters and over 60,000 words, it documents how the EU has affected UK environmental policy and how, in turn, the UK has worked through the EU to shape wider, international thinking. It has been authored by 14 international experts, who have drawn on the findings of over 700 publications to offer an impartial and authoritative assessment of the evidence.