Noncancer comparators in cancer survivorship studies

In their article on new directions in cancer and aging, Kobayashi et al discuss the important issue of control selection in cancer survivorship studies. As in all areas of epidemiology and health services research, the scientific question should drive the choice of comparison groups. We believe that it is helpful to consider the comparators needed to address 3 distinct types of survivorship questions

Pharmacoepidemiology and Drug Safety's special issue on validation studies

Administrative claims and other routinely collected data provide the foundation for many drug utilization, safety, and effectiveness studies. These databases provide a rich source of timely health care information on large, well‐defined populations. Yet information contained in these databases is generally captured using standardized systems, summarizing complex medical histories, clinical diagnoses, and services and therapies provided to patients. Thus, carefully designed validation studies that evaluate the accuracy of coded algorithms to identify health‐related exposures, outcomes, and covariates against a reference standard are an essential component for demonstrating the validity of their use for research purposes

Young-Onset Colorectal Cancer: Earlier Diagnoses or Increasing Disease Burden?

Colorectal cancer (CRC) incidence and mortality in the United States have changed strikingly in recent decades. Overall, CRC incidence decreased by >30% from 1975 (59.5 per 100,000) to 2013 (37.9 per 100,000). CRC mortality similarly declined from 28.1 per 100,000 in 1975 to 14.5 per 100,000 in 2013—nearly a 50% decrease.1 Screen-eligible populations, particularly those over age 65, have experienced the largest declines in incidence and mortality

Considering the totality of evidence: Combining real-world data with clinical trial results to better inform decision-making

Clinical trials are the key mechanism for testing efficacy of cancer therapy. While results from clinical trials have high internal validity, generalizability is limited due to strict criteria for inclusion and exclusion (i.e., eligibility criteria). Indeed, eligibility criteria are designed to protect the safety of trial participants by excluding those expected to have low efficacy or high toxicity from the treatment under investigation. However, if overly restrictive, eligibility criteria can also result in narrow populations that do not reflect the general population treated in routine practice. Recent analyses of cancer clinical trial data have shown that eligibility criteria have become increasingly restrictive, ranging from 16 to 32 exclusion criteria per trial, over time. Therefore, it is not surprising that <5% of US adult patients with cancer participate in clinical trials, and those who do are often younger and healthier than patients seen in clinical practice. These differences raise serious concern that the “efficacy” of cancer therapies reported in published clinical trials provides incomplete evidence of their “effectiveness” when administered to patients in routine care

Initiator Types and the Causal Question of the Prevalent New-User Design: A Simulation Study

New-user designs restricting to treatment initiators have become the preferred design for studying drug comparative safety and effectiveness using nonexperimental data. This design reduces confounding by indication and healthy-adherer bias at the cost of smaller study sizes and reduced external validity, particularly when assessing a newly approved treatment compared with standard treatment. The prevalent new-user design includes adopters of a new treatment who switched from or previously used standard treatment (i.e., the comparator), expanding study sample size and potentially broadening the study population for inference. Previous work has suggested the use of time-conditional propensity-score matching to mitigate prevalent user bias. In this study, we describe 3 "types"of initiators of a treatment: new users, direct switchers, and delayed switchers. Using these initiator types, we articulate the causal questions answered by the prevalent new-user design and compare them with those answered by the new-user design. We then show, using simulation, how conditioning on time since initiating the comparator (rather than full treatment history) can still result in a biased estimate of the treatment effect. When implemented properly, the prevalent new-user design estimates new and important causal effects distinct from the new-user design

Predictors of prevalent statin use among older adults identified as statin initiators based on Medicare claims data

Purpose: Few studies have evaluated the degree to which prescription drug initiators are correctly identified using claims data. We examine the prevalence and predictors of recent statin possession in statin initiators identified using claims data. Methods: Among Medicare Current Beneficiary Survey (MCBS) respondents, we used Medicare Part D claims from 2006 to 2011 to identify statin initiators using a 12-month baseline period of no prior statin claims. Using MCBS interview data, we identified those with self-reported statins obtained during the baseline period. We used log-binomial regression to estimate adjusted prevalence ratios (adjPR) and 95% confidence intervals (CI) for predictors of recent statin possession. Results: Among 766 statin initiators identified in prescription claims, 155 (20%) reported recent statin possession during baseline. Beneficiaries with no Part D claims in the past 30 days (adjPR = 1.49, 95%CI: 1.13, 1.96), those with no inpatient, outpatient or physician visits in the past 30 days (adjPR = 1.50, 95%CI: 1.11, 2.03), those with a brand name statin index claim (adjPR = 1.55, 95%CI: 1.19, 2.02), and those with an index claim in January or February (adjPR = 1.50, 95%CI: 1.00, 2.26) had an increased probability of recent statin possession. Conclusions: In a cohort of statin initiators identified using prescription claims, 20% had evidence of statin possession during the baseline period. Pharmacoepidemiologic new user studies may benefit from including sensitivity analyses within subgroups less likely to include prevalent users to assess the robustness of key findings to misidentification of the time of treatment initiation

Evaluating the Strength of the Association Between Industry Payments and Prescribing Practices in Oncology

Background: Financial relationships between physicians and the pharmaceutical industry are common, but factors that may determine whether such relationships result in physician practice changes are unknown. Materials and Methods: We evaluated physician use of orally administered cancer drugs for four cancers: prostate (abiraterone, enzalutamide), renal cell (axitinib, everolimus, pazopanib, sorafenib, sunitinib), lung (afatinib, erlotinib), and chronic myeloid leukemia (CML; dasatinib, imatinib, nilotinib). Separate physician cohorts were defined for each cancer type by prescribing history. The primary exposure was the number of calendar years during 2013–2015 in which a physician received payments from the manufacturer of one of the studied drugs; the outcome was relative prescribing of that drug in 2015, compared with the other drugs for that cancer. We evaluated whether practice setting at a National Cancer Institute (NCI)-designated Comprehensive Cancer Center, receipt of payments for purposes other than education or research (compensation payments), maximum annual dollar value received, and institutional conflict-of-interest policies were associated with the strength of the payment-prescribing association. We used modified Poisson regression to control confounding by other physician characteristics. Results: Physicians who received payments for a drug in all 3 years had increased prescribing of that drug (compared with 0 years), for renal cell (relative risk [RR] 1.81, 95% confidence interval [CI] 1.58–2.07), CML (RR 1.22, 95% CI 1.08–1.39), and lung (RR 1.69, 95% CI 1.58–1.82), but not prostate (RR 0.97, 95% CI 0.93–1.02). Physicians who received compensation payments or >$100 annually had increased prescribing compared with those who did not, but NCI setting and institutional conflict-of-interest policies were not consistently associated with the direction of prescribing change. Conclusion: The association between industry payments and cancer drug prescribing was greatest among physicians who received payments consistently (within each calendar year). Receipt of payments for compensation purposes, such as for consulting or travel, and higher dollar value of payments were also associated with increased prescribing. Implications for Practice: Financial payments from pharmaceutical companies are common among oncologists. It is known from prior work that oncologists tend to prescribe more of the drugs made by companies that have given them money. By combining records of industry gifts with prescribing records, this study identifies the consistency of payments over time, the dollar value of payments, and payments for compensation as factors that may strengthen the association between receiving payments and increased prescribing of that company's drug

No Increase in Risk of Acute Myocardial Infarction in Privately Insured Adults Prescribed Proton Pump Inhibitors vs Histamine-2 Receptor Antagonists (2002–2014)

Background & Aims: Proton pump inhibitors (PPIs) are commonly used medications. Recent studies reported an increased risk of acute myocardial infarction (MI) in PPI users vs non-users. We evaluated MI risk associated with PPIs compared with histamine-2 receptor antagonists (H2RAs) in privately insured adults in the United States. Methods: Using administrative claims from commercial and Medicare Supplemental plans (2001–2014), we compared risk of MI in patients who started a new prescription for PPIs vs H2RAs. Enrollees were followed from their first prescription until MI, medication discontinuation, plan disenrollment, or December 31, 2014. MI was defined using hospital diagnosis codes. Risk differences (RD), risk ratios, and 95% confidence intervals (CIs) were estimated using Kaplan-Meier methods at 3, 12, and 36 months after treatment initiation. Standardized morbidity ratio weights were used to control measured confounding. Analyses were stratified by plan type (commercial vs Medicare Supplemental). Results: We identified more than 5 million new users of prescription PPIs and H2RAs. Median follow-up time was 60 days for patients with commercial insurance and 96 days in patients with Medicare Supplemental insurance. The 12-month weighted risk of MI was low overall (approximately 2 cases per 1000 among patients in commercial plans; 8 per 1000 among patients in Medicare Supplemental plans). In the RD analysis, we found no significant differences in MI risk between patients who started PPIs vs H2RAs for the first 12 months, either in the commercial population (weighted RD per 1000, –0.08; 95% CI, –0.51 to 0.36) or the Medicare Supplemental population (weighted RD per 1000, –0.45; 95% CI, –1.53 to 0.58). Conclusion: In an analysis of administrative claims from commercial and Medicare Supplemental plans, we found no evidence that prescription PPIs increase risk of MI compared with prescription H2RAs. Physicians and patients should not avoid starting a PPI because of concerns related to MI risk

Thermodynamic Bethe Ansatz of the Homogeneous Sine-Gordon models

We apply the thermodynamic Bethe Ansatz to investigate the high energy behaviour of a class of scattering matrices which have recently been proposed to describe the Homogeneous sine-Gordon models related to simply laced Lie algebras. A characteristic feature is that some elements of the suggested S-matrices are not parity invariant and contain resonance shifts which allow for the formation of unstable bound states. From the Lagrangian point of view these models may be viewed as integrable perturbations of WZNW-coset models and in our analysis we recover indeed in the deep ultraviolet regime the effective central charge related to these cosets, supporting therefore the S-matrix proposal. For the $SU(3)_k$-model we present a detailed numerical analysis of the scaling function which exhibits the well known staircase pattern for theories involving resonance parameters, indicating the energy scales of stable and unstable particles. We demonstrate that, as a consequence of the interplay between the mass scale and the resonance parameter, the ultraviolet limit of the HSG-model may be viewed alternatively as a massless ultraviolet-infrared-flow between different conformal cosets. For $k=2$ we recover as a subsystem the flow between the tricritical Ising and the Ising model.Comment: 30 pages Latex, two figure

Constraining the period of the ringed secondary companion to the young star J1407 with photographic plates

Context. The 16 Myr old star 1SWASP J140747.93-394542.6 (V1400 Cen) underwent a series of complex eclipses in May 2007, interpreted as the transit of a giant Hill sphere filling debris ring system around a secondary companion, J1407b. No other eclipses have since been detected, although other measurements have constrained but not uniquely determined the orbital period of J1407b. Finding another eclipse towards J1407 will help determine the orbital period of the system, the geometry of the proposed ring system and enable planning of further observations to characterize the material within these putative rings. Aims. We carry out a search for other eclipses in photometric data of J1407 with the aim of constraining the orbital period of J1407b. Methods. We present photometry from archival photographic plates from the Harvard DASCH survey, and Bamberg and Sonneberg Observatories, in order to place additional constraints on the orbital period of J1407b by searching for other dimming and eclipse events. Using a visual inspection of all 387 plates and a period-folding algorithm we performed a search for other eclipses in these data sets. Results. We find no other deep eclipses in the data spanning from 1890 to 1990, nor in recent time-series photometry from 2012-2018. Conclusions. We rule out a large fraction of putative orbital periods for J1407b from 5 to 20 years. These limits are still marginally consistent with a large Hill sphere filling ring system surrounding a brown dwarf companion in a bound elliptical orbit about J1407. Issues with the stability of any rings combined with the lack of detection of another eclipse, suggests that J1407b may not be bound to J1407.Comment: 8 pages, 3 tables, 4 figures, accepted for publication in A&A. LaTeX files of the paper, scripts for the figures, and a minimal working FPA can be found under https://github.com/robinmentel/Constraining-Period