The efficacy‐effectiveness (EE) gap describes the differences in survival seen in clinical trials and routine clinical practice, where patients in real‐world practice often have inferior outcomes ...compared to trial populations. However, EE gaps may exist beyond survival outcomes, including gaps in quality of life, toxicity, cost‐effectiveness, and patient time, and these EE gaps should also influence patient and clinician treatment decisions. Failure to clearly acknowledge these EE gaps may cause patients, clinicians, and health care systems to have unrealistic expectations of the benefits of therapy across a range of important clinical and economic domains. In this commentary, the authors review the evidence supporting the existence of EE gaps in quality of life, time toxicity, cost and toxicities, and urge for further research into this important topic.
Efficacy‐effectiveness (EE) gaps are typically associated with survival outcomes. In this commentary, the authors review potential EE gaps in quality of life, toxicity, cost‐effectiveness, and patient time and how these EE gaps may cause patients, clinicians, and health care systems to have unrealistic expectations of the benefits of therapy across a range of clinical and economic domains.
Lower socioeconomic status (SES) is associated with worsened cancer survival. The authors evaluate the impact of SES on stage of cancer at diagnosis and survival in Ontario, Canada.
All incident ...cases of breast, colon, rectal, nonsmall cell lung, cervical, and laryngeal cancer diagnosed in Ontario during the years 2003-2007 were identified by using the Ontario Cancer Registry. Stage information is captured routinely for patients seen at Ontario's 8 Regional Cancer Centers (RCCs). The Ontario population was divided into quintiles (Q1-Q5) based on community median household income reported in the 2001 census; Q1 represents the poorest communities. Overall survival (OS) and cancer-specific survival (CSS) were determined with Kaplan-Meier methodology. A Cox model was used to evaluate the association between survival and SES, stage, and age.
Stage at diagnosis was available for 38,431 of 44,802 (85%) of cases seen at RCCs. The authors observed only very small differences in stage distribution by SES. Across all cases in Ontario, the authors found substantial gradients in 5-year OS and 3-year CSS across Q1 and Q5 for breast (7% absolute difference in OS, P < .001; 4% CSS, P < .001), colon (8% OS, P < .001; 3% CSS, P = .002), rectal (9% OS, P < .001; 4% CSS, P = .096), nonsmall cell lung (3% OS, P = .002; 2% CSS, P = .317), cervical (16% OS, P < .001; 10% CSS, P = .118), and laryngeal cancers (1% OS, P = .045; 3% CSS, P = .011). Adjustments for stage and age slightly diminished the survival gradient only among patients with breast cancer.
Despite universal healthcare, SES remains associated with survival among patients with cancer in Ontario, Canada. Disparities in outcome were not explained by differences in stage of cancer at time of diagnosis.
Introduction
Palliative chemotherapy (PC) is associated with a modest survival benefit in patients with incurable esophageal and gastric cancer; however, changes in symptom profile during treatment ...are not well described. Understanding the trajectory of symptoms during treatment may lead to improved care and facilitate shared decision making. In this study, we address this knowledge gap among all patients receiving PC in the Canadian province of Ontario.
Methods
Patients diagnosed with incurable esophageal and gastric cancer who received PC from 2012 to 2017 were identified from the Ontario Cancer Registry. Patients with one or more recorded Edmonton Symptom Assessment System (ESAS) scores in the 12 months following cancer diagnosis were included. The ESAS includes scores from 0 to 10 in nine domains (anxiety, depression, drowsiness, lack of appetite, nausea, pain, shortness of breath, tiredness, and lack of well-being). Symptom severity is categorized as none–mild (≤ 3), moderate (4–6), or severe (7–10). We focused on potentially modifiable symptoms, i.e. nausea, pain, and anxiety/depression. Logistic regression was used to identify factors associated with moderate–severe ESAS scores in these domains. Among those patients with serial ESAS scores (at 8 ± 2 and 12 ± 2 weeks) receiving chemotherapy, we describe changes during treatment (decrease by ≥ 1 = improved; − 1 > 0 > 1 = unchanged; increase by ≥ 1 = deteriorated).
Results
The cohort included 1900 patients who received PC, of whom 79% (1497/1900) had one or more recorded ESAS scores. In multivariate analysis, younger patients were more likely to have moderate–severe scores in nausea (odds ratio OR 1.89, 95% confidence interval CI 1.23–2.90
p
< 0.01 in patients aged 41–50 years compared with patients aged ≥ 71 years) and pain (OR 1.88, 95% CI 1.36–2.60
p
< 0.01 in patients aged 51–60 years compared with patients aged ≥ 71 years). Compared with males, females were more likely to report moderate–severe scores in anxiety/depression (OR 1.58, 95% CI 1.21–2.08
p
< 0.01). At 8 ± 2 weeks from PC initiation, symptom scores were unchanged in 19–42% of patients, improved in 30–51% of patients, and deteriorated in 17–35% of patients. The greatest change in symptom burden was observed for appetite (51% improvement) and anxiety/depression (35% deterioration). Similar trends were observed at 12 ± 2 weeks.
Conclusions
In this large, population-based study, we observed that younger patients were more likely to report moderate–severe symptoms in pain and nausea, and females were more likely to report moderate–severe symptoms in anxiety/depression. Anxiety/depression symptoms become increasingly problematic for a substantial proportion of patients receiving PC. Supportive care efforts to mitigate these symptoms in routine practice are needed.
Background
Clinical practice guidelines (CPGs) are crucial to the practice of evidence‐based medicine. Declared author financial conflicts of interest (FCOIs) are common in CPGs and have been ...associated with endorsement of treatment. Less is known about undeclared FCOIs.
Methods
The American Society of Clinical Oncology (ASCO) website was searched to identify all CPGs for systemic therapy published between August 2013 and June 2018. Data on self‐reported author FCOIs and funding sources were extracted. The Open Payments database was then searched to identify compensation to CPG authors. Concordance between declared and undeclared but verified FCOIs was assessed with Cohen's κ.
Results
For 26 CPGs, 314 nonduplicate authors were identified; 184 of these authors (59%) disclosed FCOIs. Among the remaining 130 authors, data in Open Payments were unavailable for 71 authors (non‐US residents or authors affiliated with a nonprofit organization). Among the 59 authors who declared no FCOIs and for whom Open Payments data were available, 55 (93%) had received payment from industry. The κ value for agreement between disclosed and verified FCOIs was 0.092. Among the 243 authors with FCOIs verifiable via Open Payments, 239 (98%) received payment from industry. Thirty‐four authors (62%) received more than $1000 in nonresearch funding, and 19 (35%) received more than $5000. Among the 52 first and last authors, 44 (85%) received payment from industry; 14 of these payments (32%) were not declared.
Conclusions
FCOIs among authors of ASCO CPGs are common and are not disclosed by a substantial proportion of authors with Open Payments data. Improved transparency of FCOIs should become standard practice among CPG authors. Professional societies and journal editors need to create a mechanism to verify self‐reported FCOIs.
Results show that financial conflicts of interest among authors of American Society of Clinical Oncology guidelines are common and are not disclosed by a substantial proportion of these authors. It is concluded that improved transparency of financial conflicts of interest should become standard practice among authors of clinical practice guidelines and that professional societies and journal editors should create a mechanism to verify self‐reported conflicts.
Adjuvant chemotherapy (AC) improves survival among patients with resected colorectal cancer. However, the optimal timing from surgery to initiation of AC is unknown.
To determine the relationship ...between time to AC and survival outcomes via a systematic review and meta-analysis. data sources: MEDLINE (1975 through January 2011), EMBASE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched to identify studies that described the relationship between time to AC and survival.
Studies were only included if the relevant prognostic factors were adequately described and either comparative groups were balanced or results adjusted for these prognostic factors.
Hazard ratios (HRs) for overall survival and disease-free survival from each study were converted to a regression coefficient (β) and standard error corresponding to a continuous representation per 4 weeks of time to AC. The adjusted β from individual studies were combined using a fixed-effects model. Inverse variance (1/SE(2)) was used to weight individual studies. Publication bias was investigated using the trim and fill approach.
We identified 10 eligible studies involving 15,410 patients (7 published articles, 3 abstracts). Nine of the studies were cohort or population based and 1 was a secondary analysis from a randomized trial of chemotherapy. Six studies reported time to AC as a binary variable and 4 as 3 or more categories. Meta-analysis demonstrated that a 4-week increase in time to AC was associated with a significant decrease in both overall survival (HR, 1.14; 95% confidence interval CI, 1.10-1.17) and disease-free survival (HR, 1.14; 95% CI, 1.10-1.18). There was no significant heterogeneity among included studies. Results remained significant after adjustment for potential publication bias and when the analysis was repeated to exclude studies of largest weight.
In a meta-analysis of the available literature on time to AC, longer time to AC was associated with worse survival among patients with resected colorectal cancer.
The phase 3 PROfound trial led to the recent approval of the PARP inhibitor olaparib for men with metastatic castration-resistant prostate cancer and mutations in homologous recombination repair ...genes. We raise methodological concerns about the trial, including: a suboptimal control arm, problematic use of crossover, use of radiographic progression-free survival as the primary endpoint, and ambiguous benefit for patients with mutations in homologous recombination repair genes other than BRCA1, BRCA2, and ATM.
In sub-Saharan Africa (SSA), urgent action is needed to curb a growing crisis in cancer incidence and mortality. Without rapid interventions, data estimates show a major increase in cancer mortality ...from 520 348 in 2020 to about 1 million deaths per year by 2030. Here, we detail the state of cancer in SSA, recommend key actions on the basis of analysis, and highlight case studies and successful models that can be emulated, adapted, or improved across the region to reduce the growing cancer crises. Recommended actions begin with the need to develop or update national cancer control plans in each country. Plans must include childhood cancer plans, managing comorbidities such as HIV and malnutrition, a reliable and predictable supply of medication, and the provision of psychosocial, supportive, and palliative care. Plans should also engage traditional, complementary, and alternative medical practices employed by more than 80% of SSA populations and pathways to reduce missed diagnoses and late referrals. More substantial investment is needed in developing cancer registries and cancer diagnostics for core cancer tests. We show that investments in, and increased adoption of, some approaches used during the COVID-19 pandemic, such as hypofractionated radiotherapy and telehealth, can substantially increase access to cancer care in Africa, accelerate cancer prevention and control efforts, increase survival, and save billions of US dollars over the next decade. The involvement of African First Ladies in cancer prevention efforts represents one practical approach that should be amplified across SSA. Moreover, investments in workforce training are crucial to prevent millions of avoidable deaths by 2030. We present a framework that can be used to strategically plan cancer research enhancement in SSA, with investments in research that can produce a return on investment and help drive policy and effective collaborations. Expansion of universal health coverage to incorporate cancer into essential benefits packages is also vital. Implementation of the recommended actions in this Commission will be crucial for reducing the growing cancer crises in SSA and achieving political commitments to the UN Sustainable Development Goals to reduce premature mortality from non-communicable diseases by a third by 2030.
The randomized clinical trial (RCT) in oncology has evolved since its widespread adoption in the 1970s. In recent years, concerns have emerged regarding the use of putative surrogate end points, such ...as progression-free survival (PFS), and marginal effect sizes.
To describe contemporary trends in oncology RCTs and compare these findings with earlier eras of RCT design and output.
Retrospective cohort study of systemic therapy RCTs in breast, colorectal, and non-small cell lung cancer published in 7 major journals between 2010 and 2020. This strategy replicates prior work and allows for comparison of trends with RCTs published between 1995 to 2004 and 2005 to 2009.
Data on RCT design, funding, results, and reporting were extracted from the published RCT report. Findings from the current period (2010-2020) were compared with data from RCTs published from 1995 to 2004 and 2005 to 2009. Descriptive and bivariate statistics were used to analyze temporal trends.
The cohort included 298 RCTs (132 44% breast, 111 37% non-small cell lung cancer, 55 19% colorectal cancer). Experimental treatment included molecular inhibitor (171 of 298 57%), cytotoxic (83 of 298 28%), hormone (15 of 298 5%), and immune (24 of 298 8%) therapies. Sixty-nine percent (206 of 298) of RCTs were of palliative intent. The most common primary end point is now PFS; this has increased substantially over time (from 0% 0 of 167 to 18% 25 of 137 to 42% 125 of 298; P < .001). Of 298 RCTs, 265 (89%) are now funded by industry (previously 95 of 167 57% and 107 of 137 78%; P < .001). Fifty-eight percent (173 of 298) of trials met their primary end point. Among positive trials, median improvement in overall survival and PFS was 3.4 and 2.9 months, respectively. More than one-third (117 of 298 39%) of reports used a professional medical writer; this increased substantially during the study period (from 3 of 27 11% in 2010 to 12 of 18 67% in 2020; P < .001).
This cohort study suggests that contemporary oncology RCTs now largely measure putative surrogate end points and are almost exclusively funded by the pharmaceutical industry. The increasing role of medical writers warrants attention. To demonstrate that new cancer treatments are high value, the oncology community needs to consider the extent to which study end points and target effect size provide meaningful benefit to patients.
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