Achieving Benchmarks for National Quality Indicators Reduces Recurrence and Progression in Non-muscle-invasive Bladder Cancer.

BACKGROUND: Noncompliance with evidence-based interventions and guidelines contributes to significant and variable recurrence and progression in patients with non-muscle-invasive bladder cancer (NMIBC). The implementation of a quality performance indicator (QPI) programme in Scotland's National Health Service (NHS) aimed to improve cancer outcomes and reduce nationwide variance. OBJECTIVE: To evaluate the effect of hospitals achieving benchmarks for two specific QPIs on time to recurrence and progression in NMIBC. DESIGN, SETTING, AND PARTICIPANTS: QPIs for bladder cancer (BC) were enforced nationally in April 2014. NHS health boards collected prospective data on all new BC patients. Prospectively recorded surveillance data were pooled from 12 collaborating centres. INTERVENTION: QPIs of interest were (1) hospitals achieving detrusor muscle (DM) sampling target at initial transurethral resection of bladder tumour (TURBT) and (2) use of single instillation of mitomycin C after TURBT (SI-MMC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary and secondary endpoints were time to recurrence and progression, respectively. Kaplan-Meier and Cox multivariable regression analyses were performed. KEY FINDINGS AND LIMITATIONS: Between April 1, 2014 and March 31, 2017, we diagnosed 3899 patients with new BC, of which 2688 were NMIBC . With a median follow up of 60.3 mo, hospitals achieving the DM sampling target had a 5.4% lower recurrence rate at 5 yr than hospitals not achieving this target (442/1136 [38.9%] vs 677/1528 [44.3%], 95% confidence interval [CI] = 1.6-9.2, p = 0.005). SI-MMC was associated with a 20.4% lower recurrence rate (634/1791 [35.4%] vs 469/840 [55.8%], 95% CI = 16.4-24.5, p < 0.001). On Cox multivariable regression, meeting the DM target and SI-MMC were associated with significant improvement in recurrence (hazard ratio [HR] 0.81, 95% CI = 0.73-0.91, p = 0.0002 and HR 0.66, 95% CI = 0.59-0.74, p < 0.004, respectively) as well as progression-free survival (HR 0.62, 95% CI = 0.45-0.84, p = 0.002 and HR 0.65, 95% CI = 0.49-0.87, p = 0.004, respectively). We did not have a national multicentre pre-QPI control. CONCLUSIONS: Within a national QPI programme, meeting targets for sampling DM and SI-MMC in the real world were independently associated with delays to recurrence and progression in NMIBC patients. PATIENT SUMMARY: Following the first 3 yr of implementing a novel quality performance indicator programme in Scotland, we evaluated compliance and outcomes in non-muscle-invasive bladder cancer. In 2688 patients followed up for 5 yr, we found that achieving targets for sampling detrusor muscle and the single instillation of mitomycin C during and after transurethral resection of bladder tumour, respectively, were associated with delays in cancer recurrence and progression.

Precision oncology medicines and the need for real world evidence acceptance in health technology assessment: Importance of patient involvement in sustainable healthcare.

Precision oncology has made remarkable strides in improving clinical outcomes, offering hope to patients with historically difficult-to-treat, as well as rare or neglected cancers. However, despite rapid advancement, precision oncology has reached a critical juncture, where patient access to these life-saving medicines may be hampered by strict requirements by Health Technology Assessment (HTA) bodies for randomised controlled trials (RCTs) for assessing new medicines against appropriate comparator. The very nature of precision oncology-matching a tumour's unique molecular alterations to targeted therapies predicted to elicit response-can make the use of RCTs very difficult, as only a very small number of patients might qualify for a given therapy within a traditional clinical trial setting. Real-world evidence (RWE) has been accepted for regulatory decision-making but has yet to reach widespread acceptance by HTA bodies. As the oncology treatment landscape has evolved towards favouring the concept of precision oncology, there is a growing need for flexibility in the way HTA bodies evaluate new medicines. We must acknowledge that current assessment methodologies can limit access to life-changing medicines for many patients who have no alternative options and that a growing number of precision oncology medicines with proven clinical benefits in rare tumours cannot be reasonably evaluated using traditional methodologies. The objectives of this paper are to advocate a change in mindset regarding best practices in drug assessment models and to propose alternative approaches when considering indications for which RWE is the most compelling data source available.

Redefining Cancer Research Priorities in Low- and Middle-Income Countries in the Post-COVID-19 Global Context: A Modified Delphi Consensus Process.

PURPOSE: The post-COVID-19 funding landscape for cancer research globally has become increasingly challenging, particularly in resource-challenged regions (RCRs) lacking strong research ecosystems. We aimed to produce a list of priority areas for cancer research in countries with limited resources, informed by researchers and patients. METHODS: Cancer experts in lower-resource health care systems (as defined by the World Bank as low- and middle-income countries; N = 151) were contacted to participate in a modified consensus-seeking Delphi survey, comprising two rounds. In round 1, participants (n = 69) rated predetermined areas of potential research priority (ARPs) for importance and suggested missing ARPs. In round 2, the same participants (n = 49) rated an integrated list of predetermined and suggested ARPs from round 1, then undertook a forced choice priority ranking exercise. Composite voting scores (T-scores) were used to rank the ARPs. Importance ratings were summarized descriptively. Findings were discussed with international patient advocacy organization representatives. RESULTS: The top ARP was research into strategies adapting guidelines or treatment strategies in line with available resources (particularly systemic therapy) (T = 83). Others included cancer registries (T = 62); prevention (T = 52); end-of-life care (T = 53); and value-based and affordable care (T = 51). The top COVID-19/cancer ARP was strategies to incorporate what has been learned during the pandemic that can be maintained posteriorly (T = 36). Others included treatment schedule interruption (T = 24); cost-effective reduction of COVID-19 morbidity/mortality (T = 19); and pandemic preparedness (T = 18). CONCLUSION: Areas of strategic priority favored by cancer researchers in RCRs are related to adaptive treatment guidelines; sustainable implementation of cancer registries; prevention strategies; value-based and affordable cancer care; investments in research capacity building; epidemiologic work on local risk factors for cancer; and combatting inequities of prevention and care access.

Strategic career building during your PhD: a timeline for maximizing your opportunities.

PhD training can be incredibly versatile, leading to many downstream careers. There is potential to gain training to help you enter any of these careers after graduation. However, it is often only in retrospect that the options and optimal strategies become clear. Here we provide a strategic framework to empower PhD researchers to build and expand their career options in a method compatible with tomorrow's career ecosystem. The strategic framework encourages early career researchers to take a self-directed approach to establish flexible career goals, diversify exposures and build professional networks. Researchers increase their chances of success by building early markers of multiple career pathways into their PhD program. The framework emphasizes self-direction, adaptability and resilience, enabling early career researchers to embrace new opportunities and to navigate uncertainties. This structured approach empowers PhD researchers to maximize their opportunities, positioning them for long-term success in the various career options within and beyond academia.

Diagnosis, treatment and survival from bladder, upper urinary tract, and urethral cancers: real-world findings from NHS England between 2013 and 2019.

OBJECTIVE: We report NHS England data for patients with bladder cancer (BC), upper tract urothelial cancer (UTUC: renal pelvic and ureteric), and urethral cancers from 2013 to 2019. MATERIALS AND METHODS: Hospital episode statistics, waiting times, and cancer registrations were extracted from NHS Digital. RESULTS: Registrations included 128 823 individuals with BC, 16 018 with UTUC, and 2533 with urethral cancer. In 2019, 150 816 persons were living with a diagnosis of BC, of whom 113 067 (75.0%) were men, 85 117 (56.5%) were aged >75 years, and 95 553 (91.7%) were Caucasian. Incidence rates were stable (32.7-34.3 for BC, 3.9-4.2 for UTUC and 0.6-0.7 for urethral cancer per 100 000 population). Most patients 52 097 (mean [range] 41.3% [40.7-42.0%]) were referred outside the 2-week-wait pathway and 15 340 (mean [range] 12.2% [11.7-12.6%]) presented as emergencies. Surgery, radiotherapy, chemotherapy, or multimodal treatment use varied with disease stage, patient factors and Cancer Alliance. Between 27% and 29% (n = 6616) of muscle-invasive BCs did not receive radical treatment. Survival rates reflected stage, grade, location, and tumour histology. Overall survival rates did not improve over time (relative change: 0.97, 95% confidence interval 0.97-0.97) at 2 years in contrast to other cancers. CONCLUSION: The diagnostic pathway for BC needs improvement. Increases in survival might be delivered through greater use of radical treatment. NHS Digital data offers a population-wide picture of this disease but does not allow individual outcomes to be matched with disease or patient features and key parameters can be missing or incomplete.

Disparities in Access to Novel Systemic Therapies in Patients With Urinary Tract Cancer: Propagating Access, Policies and Resources Uniformly.

After several decades of therapeutic stagnation, the treatment of patients with urothelial carcinoma has met a revolutionary wave, anticipated by the advent of immune-checkpoint inhibitors (ICI) and followed by newer therapeutic options in the post-ICI setting. These achievements were made in a very short time-frame, thus making the treatment of this disease particularly susceptible to geographical health disparity due to the differences in healthcare systems and approval processes of the regulatory authorities. Furthermore, additional barriers to access innovative care are represented by a limited coverage of clinical trials availability, that is consistent in focusing on selected geographical areas, across trials and clinical settings. Here, we present the current picture of new drug approvals in urothelial carcinoma worldwide, and we also focus our considerations onto the spectrum of ongoing trial inclusion possibilities, trying to understand what are the current gaps in clinical research and routine practice, identifying a way to move forward.

Providing a Framework for Meaningful Patient Involvement in Clinical Practice Guideline Development and Implementation.

The importance of patient involvement in guideline development is internationally recognised, yet there is a lack of clear methodology for integrating patient preferences and values in guidelines and a need to identify the optimum stages for involving patients in guideline production. European Association of Urology (EAU) guidelines have international reach, a rigorous guideline production process, an established patient information section, and existing links with European cancer patient organisations. This makes the EAU the ideal setting to test a framework for patient involvement in guideline development for genitourinary cancers. The EVOLVE study is a unique collaboration involving a professional society, guideline panels, researchers, clinicians, and patient organisations with the aim of designing a framework for meaningful patient involvement in guideline production. Stages for considering patient preferences and values were identified via systematic review and interviews with key stakeholders, then prioritised by patients and clinicians via an international Delphi study. The final EVOLVE framework will be tested within EAU guideline panels and a strategy to assess the impact of patient involvement in guidelines will be developed. PATIENT SUMMARY: There is increasing awareness of the need to include patient values and preferences when developing guidelines for medical practice. The EVOLVE study is designing a framework for patient involvement in guideline development. TAKE HOME MESSAGE: A framework for meaningful patient involvement in guideline development and implementation has been developed. The EVOLVE framework can help guideline developers to involve patients at the optimum stages of guideline production, which may improve the quality and relevance of guidelines.

Designing a Pragmatic Intervention to Help Improve the Bladder Cancer Patient Experience.

Bladder cancer (BC) is the 10th most common malignancy worldwide and the patient experience is found to be worse than that for patients diagnosed with other cancer types. We aimed to develop a wellbeing intervention to help improve the bladder cancer patient experience by ameliorating their health-related Quality of Life (HRQoL). We followed the 3 phases of the modified Medical Research Council (MRC) Framework for development of complex interventions. Following a systematic review of the literature on mental, sexual, and physical wellbeing, we conducted discussion groups with patients and healthcare professionals on these 3 themes. A consultation phase was then conducted with all relevant stakeholders to co-design a wellbeing intervention as part of a feasibility study. A pragmatic wellbeing feasibility trial was designed based on the hypothesis that a wellbeing program will increase patient awareness and attendance to services available to them and will better support their needs to improve HRQoL. The primary feasibility endpoints are patient attendance to the services offered and changes in HRQoL. The principle of patient centered care has strengthened the commitment to provide a holistic approach to support BC patients. In this study, we developed a wellbeing intervention in collaboration with patients and healthcare professionals to meet an unmet need in terms of the BC patient experience.

Precision oncology: a clinical and patient perspective.

Molecular characterization of tumors has shifted cancer treatment strategies away from nonspecific cytotoxic treatment of histology-specific tumors toward targeting of actionable mutations that can be found across multiple cancer types. The development of high-throughput technologies such as next-generation sequencing, combined with decision support applications and availability of patient databases, has provided tools that optimize disease management. Precision oncology has proven success in improving outcomes and quality of life, as well as identifying and overcoming mechanisms of drug resistance and relapse. Addressing challenges that impede its use will improve matching of therapies to patients. Here we review the current status of precision oncology medicine, emphasizing its impact on patients - what they understand about precision oncology medicine and their hopes for the future.

Lay abstract Precision oncology offers individualized treatment of cancer on a per-patient basis, based on the unique DNA fingerprint of a patient's cancer. New, advanced technologies for DNA sequencing have led to rapid advancement in developing novel therapies. Decision-making tools have followed pace, leading to improved matching of therapy to patient, ultimately improving outcomes (including quality of life), building trust between patient and physician, and increasing hope for the future.

The call for a strategic framework to improve cancer literacy in Europe.

BACKGROUND: Health literacy is increasingly being recognized as a widespread public health challenge in Europe. This commentary explores the importance of health literacy amongst cancer patients (ie, cancer literacy) and examines how cancer literacy can be improved through the practical application of health literacy principles within the context of providing timely, patient-centered, value-based care in Europe. MAIN BODY: Despite implementation of evidence-based cancer prevention programs and increased cancer survival rates, low cancer literacy may impact the personal capacity to manage risks and adversely impact behavior and outcomes. Cancer literacy poses a unique set of challenges compared to other types of health literacy, as patient decisions regarding screening, treatment, and side effect management are often complex, and timely decision-making is more critical. Accordingly, European health policies increasingly recognize the importance of health literacy. The European Patients Forum, European Cancer Patient Coalition, and the Association of European Cancer Leagues supported a joint statement, "Europe Let's Do More for Health," which emphasizes the need to empower citizens and patients by addressing health literacy, self-management, and shared decision-making. Implementation of comprehensive programs and strategies will be important to improve health literacy. Cancer literacy can be improved through application of health literacy principles in the communication and cooperation with professionals, patients and caregivers for providing timely, patient-centered, value-based care. Recommendations are made for further action to improve cancer literacy in Europe through coordinated efforts among providers, organizations, patients, and research. A policy paper developed by the European Joint Action on Cancer Control provides practical recommendations that Member States can take to reduce social inequalities in cancer care and defines focus areas that are closely connected with the need to improve cancer literacy. CONCLUSION: Improved personal cancer literacy combined with health literate organizations and systems can potentially improve the quality of care and health outcomes among patients with cancer. National Cancer Control Plans and Europe's Beating Cancer Plan can strengthen cancer literacy.

Achieving equal and timely access to innovative anticancer drugs in the European Union (EU): summary of a multidisciplinary CECOG-driven roundtable discussion with a focus on Eastern and South-Eastern EU countries.

The Central European Cooperative Oncology Group (CECOG) and 'ESMO Open-Cancer Horizons' roundtable discussion brought together stakeholders from several European Union (EU) countries involved in drug development, drug authorisation and reimbursement or otherwise affected by delayed and unequal access to innovative anticancer drugs. The approval process of drugs is well established and access delays can be caused directly or indirectly by national or regional decision-making processes on reimbursement. The two key aspects for those involved in reimbursement decisions are first the level of evidence required to decide and second pricing, which can be challenging for some innovative oncology compounds, especially in Eastern and South-Eastern European countries. Other important factors include: available healthcare budget; the structure and sophistication of healthcare authorities and health technology assessment processes; societal context and political will. From the point of view of the pharmaceutical industry, better alignment between stakeholders in the process and adaptive pathway initiatives is desirable. Key aspects for patients are improved access to clinical trials, preapproval availability and reports on real-world evidence. Restricted access limits oncologists' daily work in Eastern and South-Eastern EU countries. The roundtable discussion suggested considering the sequencing of regulatory approval and reimbursement decisions together with more flexible contracting as a possible way forward. The panel concluded that early and regular dialogue between all stakeholders including regulators, payers, patient stakeholders and industry is required to improve the situation.

IDF Diabetes Atlas estimates of 2014 global health expenditures on diabetes.

AIMS: To estimate health expenditures due to diabetes in 2014 for the world and its regions. METHODS: Diabetes-attributable health expenditures were estimated using an attributable fraction method. Data were sourced from International Diabetes Federation (IDF) estimates of diabetes prevalence, UN population projections, WHO annual health expenditure reports, and estimates of the cost ratio of people with and without diabetes. Health expenditures were calculated in both US dollars (USD) and international dollars (ID). RESULTS: The average health expenditure per person with diabetes worldwide in 2014 was estimated to range from USD 1583 (ID 1742) to USD 2842 (ID 3110). The estimated annual global health expenditure attributable to diabetes ranged from USD 612 billion (ID 673 billion) to USD 1099 billion (ID 1202 billion). Together, the North America and Caribbean Region and the Europe Region were responsible for over 69% of the costs, and less than 10% of the costs were from the Africa Region, South East Asia Region, and Middle East and North Africa Region combined. The North America and Caribbean Region had the highest annual spending per person with diabetes (USD 7984 [ID 8040.39]), while the South East Asia Region had the lowest annual spending per person with diabetes (USD 92 [ID 234]). CONCLUSIONS: Diabetes imposes a large economic burden on health care systems across the world, yet varies across world regions. Diabetes prevention and effective management of diabetes should be a public health priority to reduce the financial burden.

Compliance with pharmacotherapy and direct healthcare costs in patients with Parkinson's disease: a retrospective claims database analysis.

BACKGROUND: Parkinson's disease (PD) is a progressive neurological disorder for which, at present, there is no cure. Current therapy is largely based on the use of dopamine agonists and dopamine replacement therapy, designed to control the signs and symptoms of the disease. The majority of current treatments are administered in tablet form and can involve multiple daily doses, which may contribute to sub-optimal compliance. Previous studies with small groups of patients suggest that non-compliance with treatment can result in poor response to therapy and may ultimately increase direct and indirect healthcare costs. OBJECTIVE: To determine the extent of non-compliance within the general PD population in the USA as well as the patient characteristics and healthcare costs associated with compliance and non-compliance. METHODS: A retrospective analysis from a managed care perspective was conducted using data from the USA PharMetrics patient-centric claims database. PharMetrics claims data were complete from 31 December 2005 to 31 December 2009. Patients were included if they had at least two diagnoses for PD between 31 December 2005 and 31 December 2008, were older than 18 years of age, were continuously enrolled for at least 12 months after the date of the most recent PD diagnosis, and had no missing or invalid data. The follow-up period was the most recent 12-month block of continuous enrollment that occurred between 2006 and 2009. Patients were required to have at least one PD-related prescription within the follow-up period. The medication possession ratio (MPR) was used to categorise patients as compliant or non-compliant. Direct all-cause annual healthcare costs for patients with PD were estimated for each patient, and regression analyses were conducted to determine predictors for non-compliance. RESULTS: A total of 15,846 patients were included, of whom 46 % were considered to be non-compliant with their prescribed medication (MPR <0.8). Predictors of non-compliance included prescription of a medication administered in multiple daily doses (p < 0.0001), a period of <2 years since the initial PD diagnosis (p = 0.0002), a diagnosis of gastrointestinal disorder (p < 0.0001), and a diagnosis of depression (p < 0.0001). Non-compliance was also found to be related to age, with a lower odds of non-compliance in patients aged 41-80 years than in patients aged ≥81 years (p < 0.05). Although total drug mean costs were higher for compliant patients than non-compliant patients (driven mainly by the cost of PD-related medications), the mean costs associated with emergency room and inpatient visits were higher for patients non-compliant with their prescribed medication. Overall, the total all-cause annual healthcare mean cost was lower for compliant ($77,499) than for non-compliant patients ($84,949; p < 0.0001). CONCLUSION: Non-compliance is prevalent within the general USA PD population and is associated with a recent PD diagnosis, certain comorbidities, and multiple daily treatment dosing. Non-compliance may increase the burden on the healthcare system because of greater resource usage compared with the compliant population. Treatments that require fewer daily doses may have the potential to improve compliance, which in turn could reduce the economic burden associated with PD.