Treatment Policy Research Articles

Threshold-awareness in adaptive cancer therapy.

Although adaptive cancer therapy shows promise in integrating evolutionary dynamics into treatment scheduling, the stochastic nature of cancer evolution has seldom been taken into account. Various sources of random perturbations can impact the evolution of heterogeneous tumors, making performance metrics of any treatment policy random as well. In this paper, we propose an efficient method for selecting optimal adaptive treatment policies under randomly evolving tumor dynamics. The goal is to improve the cumulative "cost" of treatment, a combination of the total amount of drugs used and the total treatment time. As this cost also becomes random in any stochastic setting, we maximize the probability of reaching the treatment goals (tumor stabilization or eradication) without exceeding a pre-specified cost threshold (or a "budget"). We use a novel Stochastic Optimal Control formulation and Dynamic Programming to find such "threshold-aware" optimal treatment policies. Our approach enables an efficient algorithm to compute these policies for a range of threshold values simultaneously. Compared to treatment plans shown to be optimal in a deterministic setting, the new "threshold-aware" policies significantly improve the chances of the therapy succeeding under the budget, which is correlated with a lower general drug usage. We illustrate this method using two specific examples, but our approach is far more general and provides a new tool for optimizing adaptive therapies based on a broad range of stochastic cancer models.

Screening for antifolate and artemisinin resistance in Plasmodium falciparum dried-blood spots from three hospitals of Eritrea

Background Antimalarial drug resistance is a major challenge hampering malaria control and elimination. About three-quarters of Eritrea’s population resides in the malaria-endemic western lowlands of the country. Plasmodium falciparum, the leading causative parasite species, has developed resistance to basically all antimalarials. Continued surveillance of drug resistance using genetic markers provides important molecular data for treatment policies which complements clinical studies, and strengthens control efforts. This study sought to genotype point mutations associated with P. falciparum resistance to sulfadoxine-pyrimethamine and artemisinin, in dried-blood spots from three hospitals in the western lowlands of Eritrea. Methods Dried-blood spot samples were collected from patients visiting Adi Quala, Keren and Gash Barka Hospitals, between July and October, 2014. The patients were followed up after treatment with first line artesunate-amodiaquine, and dried-blood spots were collected on day three after treatment. Nested polymerase chain reaction and Sanger sequencing techniques were employed to genotype point mutations in the Pfdhfr (PF3D7_0417200), Pfdhps (PF3D7_0810800) and PfK13 (PF3D7_1343700) partial gene regions. Results Sequence data analyses of PCR-positive isolates found wild-type artemisinin haplotypes associated with resistance (Y493Y, R539R, I543I) in three isolates, whereas four mutant antifolate haplotypes associated with resistance were observed in six isolates. These included the triple-mutant Pfdhfr (S108N, C59R, N51I) haplotype, the double-mutant Pfdhfr (N51I, S108N) haplotype, the single-mutant Pfdhfr (K540E) haplotype, and the mixed-mutant Pfdhfr-Pfdhps (S108N, N51I + K540E) haplotype. Other findings observed were, a rare non-synonymous Pfdhfr V45A mutation in four isolates, and a synonymous Pfdhps R449R in one isolate. Conclusions The mutant antifolate haplotypes observed indicate a likely existence of full SP resistance. Further studies can be carried out to estimate the prevalence of SP resistance. The wild-type artemisinin haplotypes observed suggest artemisinin is still an effective treatment. Continuous monitoring of point mutations associated with delayed parasite clearance in ART clinical studies is recommended.

Prevalence of Neisseria gonorrhoeae, Chlamydia trachomatis, Ureaplasma urealyticum among outpatients in central China: A retrospective study

Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Ureaplasma urealyticum (UU) are the common sexually transmitted pathogens and lead to genital diseases, highly prevalent all around the world. The objective of this study was to analyze the prevalence of NG, CT and UU among outpatients in central China. A total of 2186 urogenital swabs were collected from the patients and the NG, CT and UU pathogens were testing with RT-PCR method, meanwhile the medical records were obtained from the hospital information system. The overall infection rates of NG, CT and UU were 4.57 %, 6.63 % and 48.81 % respectively, showed the prevalence of UU was higher than NG and CT. The younger people had the highest infection rate of NG (10.81 %), CT (20.54 %) and UU (54.59 %). Single infection (89.09 %) was significant higher than co-infection (10.91 %), and the CT-UU co-infection was the prominent pattern (66.41 %). There were an obvious sex difference, the prevalence of NG and CT were significant higher in male, whereas UU was higher in female. Our study could contributed a better understanding of the prevalence of NG, CT and UU, facilitating to the development of effective screening, prevention and treatment policies.

Forecasting the Economic Burden of Cardiovascular Disease and Stroke in the United States Through 2050: A Presidential Advisory From the American Heart Association.

Quantifying the economic burden of cardiovascular disease and stroke over the coming decades may inform policy, health system, and community-level interventions for prevention and treatment. We used nationally representative health, economic, and demographic data to project health care costs attributable to key cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia) and conditions (coronary heart disease, stroke, heart failure, atrial fibrillation) through 2050. The human capital approach was used to estimate productivity losses from morbidity and premature mortality due to cardiovascular conditions. One in 3 US adults received care for a cardiovascular risk factor or condition in 2020. Annual inflation-adjusted (2022 US dollars) health care costs of cardiovascular risk factors are projected to triple between 2020 and 2050, from $400 billion to $1344 billion. For cardiovascular conditions, annual health care costs are projected to almost quadruple, from $393 billion to $1490 billion, and productivity losses are projected to increase by 54%, from $234 billion to $361 billion. Stroke is projected to account for the largest absolute increase in costs. Large relative increases among the Asian American population (497%) and Hispanic American population (489%) reflect the projected increases in the size of these populations. The economic burden of cardiovascular risk factors and overt cardiovascular disease in the United States is projected to increase substantially in the coming decades. Development and deployment of cost-effective programs and policies to promote cardiovascular health are urgently needed to rein in costs and to equitably enhance population health.

Análise da atuação dos Centros Judiciários de Solução de Conflitos à luz da Agenda 2030

The National Judicial Policy for the Adequate Treatment of Conflicts of Interest (PJNTACI), developed by the National Council of Justice (CNJ), aims to disseminate the use of alternative methods of conciliation, mediation and conflict resolution, in order to make effective qualified access to justice, through the propagation of the culture of social pacification, which in turn, it is aligned with the basic principles set out by the Sustainable Development Goals (SDGs) pointed out by the UN. In this context, this paper seeks to analyze the alignment between the performance of the Judicial Centers for Conflict Resolution and Citizenship (Cejuscs) with SDG 16 which deals with "Peace, Justice and Effective Institutions" and SDG 10 which deals with "Reduction of inequalities". For this analysis, bibliographic research was carried out, with consultation of books, scientific articles, dissertations, theses and legislation. Based on the results pointed out by the analyses carried out, it is concluded that the Judicial Centers for Conflict Resolution act in accordance with the SDGs of the UN 2030 Agenda, since it provides for the resolution of legal issues between the interested parties, in a less conflictual way, in addition to exercising, free of charge, the technical services necessary for the processes of the assisted parties in question.

Cancer is not a risk factor for severe COVID-19 in children, except in patients with recent allogeneic hematopoietic stem cell transplantation or comorbidities.

The EPICO (Spanish general registry of COVID-19 in children)-SEHOP (Spanish Society of Pediatric Hematology and Oncology) platform gathers data from children with SARS-CoV-2 in Spain, allowing comparison between children with cancer or allogeneic hematopoietic stem cell transplantation (alloHSCT) and those without. The infection is milder in the cancer/alloHSCT group than in children without comorbidities (7.1% vs. 14.7%), except in children with recent alloHSCT (less than 300days), of which 35.7% experienced severe COVID-19. These data have been shared with the SEHOP members to support treatment and isolation policies akin to those for children without cancer, except for those with recent alloHSCT or additional comorbidities. This highlights the collaborative registries potential in managing pandemic emergencies.

The Relationship Between Giving Pilis (Rice, Turmeric, Sand Ginger, Ginger, Lime) and Postpartum Maternal Health

The use of traditional herbs is intended for postpartum health care and recovery. To see the benefits of using these ingredients, it is necessary to study the relationship between the provision of traditional ingredients and the health impacts on postpartum mothers who use them. This study aims to determine the relationship between giving pilis (rice, turmeric, sand ginger, ginger, lime) and the health of post-partum mothers. This type of quantitative research uses a correlational analytical research design using a cross-sectional approach. The sample in this study was 43 postpartum mothers in the ten public health centers of the Bangkalan Madura district. The data collection technique uses an observation sheet instrument. Sampling used simple random sampling nonparametric statistical analysis with analysis tests using Chi-Square. The research results showed a relationship between giving pilis (rice, turmeric, sand ginger, ginger, lime) and the health of post-partum mothers, as evidenced by a p-value of 0.000 less than 0.05. In conclusion, giving pilis to postpartum mothers continues to be maintained because of its perceived health benefits, which are in line with the expectations of the Bangkalan community. Suggestion: The development of traditional medicine from a pharmacological perspective must be carried out so that people can use traditional medicine according to standards. After development by pharmacologists, a postpartum mother treatment policy based on local, family, and community wisdom can be formulated.

#2766 Impact of CKD screening in high-risk populations and guideline-directed therapy on CV event occurrence and costs in Europe: an IMPACT CKD analysis

Abstract Background and Aims Chronic kidney disease (CKD) is a growing health problem in Europe exacerbated by aging and the rise of comorbidities such as diabetes mellitus (DM) and hypertension (HTN). Patients with CKD are often multi-morbid and commonly present with cardiovascular (CV) complications. While CV events including myocardial infarction (MI), stroke, and hospitalization for heart failure (HHF) occur more often in patients with advanced CKD, patients with early-stage CKD are also at increased risk. Patients with CKD also experience an increased risk of CV-related mortality, with many patients dying from CV events prior to kidney failure and renal replacement therapy. CV events also present a significant burden to clinicians and healthcare systems due to the high costs and resource use required to manage and treat them. Despite this multidimensional burden, CKD is currently underdiagnosed in Europe, and CKD screening and treatment are rarely included in public health strategies to improve mortality and health outcomes. This study aims to explore the impact of targeted CKD screening followed by guideline-directed therapy in high-risk populations on CV event occurrence and associated treatment costs across Europe. Method The IMPACT CKD microsimulation model simulates CKD progression, CV events, and comorbidities. CKD status is assigned based on estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio levels (UACR), and CKD progression is predicted by an annual eGFR decline rate. The model was used to compare two scenarios in four country populations (Germany, Netherlands, Spain, United Kingdom [UK]): 1) targeted screening for people with DM and/or HTN followed by optimal compliance to guideline-directed therapy and 2) current practice (no screening, underdiagnosis, low treatment rates). Annual targeted screening assumed both eGFR and UACR testing. Treatment initiation for people diagnosed with CKD was based on Kidney Disease Improving Global Outcomes guidelines with a 90% compliance assumed to approximate maximum clinical benefit. Therapies were assumed to have a multiplicative treatment effect on eGFR decline and CV events. Current practice assumed observed diagnosis rates without screening and observed treatment rates in each country. For both scenarios, the model projected incidence of CV events and associated management costs in year 10 (2032) and cumulatively over the 10 simulated years (2023-2032). Results Results compare the targeted screening followed by guideline-directed treatment scenario to continuation of current practices for Germany, Netherlands, Spain, and UK (Table 1). The timely diagnosis of patients with CKD and effective treatment was associated with a reduction of 46.7-53.3%, 38.9-41.6%, and 42.1-50.5% in the number of MI, stroke, and HHF events, respectively in 2032 across the four countries. These decreases in the number of CV events were accompanied by proportional reductions in costs to treat the events. Additionally, this policy approach resulted in declines in the cumulative 10-year CV event development and associated healthcare costs, with MI having the largest reductions (40.6-47.2%), followed by HHF (37.4-43.0%), and stroke (29.8-36.1%) across the four countries. Conclusion This study illustrated that early identification of high-risk patients with CKD coupled with guideline-directed treatment would yield substantial clinical and economic benefits from reducing CV events across all four European countries. Fewer MI, stroke, and HHF events were projected in patients with CKD in both 2032 and cumulatively from 2023 to 2032 due to delayed disease progression following effective interventions. Driven by the reduced clinical burden, lower healthcare costs for CV event management were also predicted. These findings support the need for the adoption of policies for early diagnosis and treatment of CKD to slow disease progression and mitigate the growing CV disease burden among patients with CKD and for health systems. Future studies should explore the costs associated with targeted CKD screening and the guideline-directed pharmacological therapies for CKD.

Endoscopically diagnosed hookworm infestation in an adult with chronic iron deficiency anaemia

Despite advances in hookworm control and prevention campaigns, the prevalence remains high in sub-Saharan Africa. Iron deficiency anaemia is a major complication in those with prolonged infection, a high hookworm burden, and undernutrition, though most infected people are asymptomatic. While infected patients are commonly diagnosed by the presence of ova or cysts in the stool, gastrointestinal (GI) endoscopy is required for those with negative stool tests and chronic iron deficiency anaemia. A 48-year-old female with symptoms of anaemia for nearly two years presented to Mbarara Regional Referral Hospital with worsening palpitations, easy fatigability, and dizziness over a period of one month. She was given blood transfusions on two occasions. She lives near the lake where she also gets water for drinking and domestic use. We advise GI endoscopy for all patients with chronic iron deficiency anaemia of unexplained aetiology on standard non-invasive testing. Hookworm’s mass empirical treatment policy in endemic areas should be further emphasised.

Markov models for clinical decision-making in radiation oncology: A systematic review.

The intrinsic stochasticity of patients' response to treatment is a major consideration for clinical decision-making in radiation therapy. Markov models are powerful tools to capture this stochasticity and render effective treatment decisions. This paper provides an overview of the Markov models for clinical decision analysis in radiation oncology. A comprehensive literature search was conducted within MEDLINE using PubMed, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only studies published from 2000 to 2023 were considered. Selected publications were summarized in two categories: (i) studies that compare two (or more) fixed treatment policies using Monte Carlo simulation and (ii) studies that seek an optimal treatment policy through Markov Decision Processes (MDPs). Relevant to the scope of this study, 61 publications were selected for detailed review. The majority of these publications (n = 56) focused on comparative analysis of two or more fixed treatment policies using Monte Carlo simulation. Classifications based on cancer site, utility measures and the type of sensitivity analysis are presented. Five publications considered MDPs with the aim of computing an optimal treatment policy; a detailed statement of the analysis and results is provided for each work. As an extension of Markov model-based simulation analysis, MDP offers a flexible framework to identify an optimal treatment policy among a possibly large set of treatment policies. However, the applications of MDPs to oncological decision-making have been understudied, and the full capacity of this framework to render complex optimal treatment decisions warrants further consideration.

A comprehensive review on human health hazards due to groundwater contamination: A global perspective

Over the past few decades, the state of groundwater has become a pressing concern, significantly impacting human health. Groundwater contamination from various pollutants poses substantial risks to communities worldwide, particularly in areas with limited access to clean water. Addressing these challenges necessitates a comprehensive approach, including source control, water quality monitoring, advanced treatment technologies, policy formulation, education, and community engagement. This review paper aims to raise awareness of the diverse factors contributing to water contamination. Examining studies on water pollution from human activities reveals that pesticides, fertilizers, industrial operations, and mining activities are major sources of contamination. Nitrate, harmful substances, and radioactive elements negatively affect the quality of both surface and groundwater, posing significant health risks, especially to vulnerable populations like children and women. Microplastic contamination, primarily from sewage discharge into oceans, poses additional concerns. Geological sources contribute to groundwater contamination through geochemical processes, with fluoride, nitrate, arsenic, uranium, manganese, and various trace elements identified as contaminants. Pharmaceutical ingredients have also been detected in drinking water and fish, albeit in minimal quantities with negligible health risks. Nonetheless, the cumulative impact of pollution sources on individual well-being and quality of life is considerable. Safeguarding groundwater quality is crucial for protecting public health and requires a combination of regulatory measures, technological advancements, community involvement, and sustainable practices. Consistent monitoring of groundwater quality is recommended to identify pollutant sources and develop effective remedial strategies, ensuring healthier and safer environments for current and future generations.

Efficient Nonparametric Estimation of Stochastic Policy Effects with Clustered Interference

Interference occurs when a unit’s treatment (or exposure) affects another unit’s outcome. In some settings, units may be grouped into clusters such that it is reasonable to assume that interference, if present, only occurs between individuals in the same cluster, that is, there is clustered interference. Various causal estimands have been proposed to quantify treatment effects under clustered interference from observational data, but these estimands either entail treatment policies lacking real-world relevance or are based on parametric propensity score models. Here, we propose new causal estimands based on modification of the propensity score distribution which may be more relevant in many contexts and are not based on parametric models. Nonparametric sample splitting estimators of the new estimands are constructed, which allow for flexible data-adaptive estimation of nuisance functions and are consistent, asymptotically normal, and efficient, converging at the usual parametric rate. Simulations show the finite sample performance of the proposed estimators. The proposed methods are applied to evaluate the effect of water, sanitation, and hygiene facilities on diarrhea among children in Senegal. Supplementary materials for this article are available online, including a standardized description of the materials available for reproducing the work.

Directors with foreign experience and employee protection

AbstractThis study investigates the impact of managerial foreign experience on corporate employee protection. Using 30,644 firm‐year observations from 3972 Chinese listed firms from 2008 to 2020, I find that compared with firms without returnee directors, firms with returnee directors pay more social insurance premiums and implement better employee treatment policies. The positive relationship is stronger when returnee directors acquire foreign work experience (as opposed to educational experience), gain experience in countries with strong labor protection, serve as a CEO or a chairperson in the Chinese firm, and have high media visibility. The cross‐sectional analysis shows the effect of directors with foreign experience on employee protection is greater in non‐state‐owned firms, and returnee directors improve employee protections more when the employees have relatively weak discourse power. Additional analysis finds that returnee directors improve employee training and occupational safety, and they help balance social insurance generosity and employment levels. The results are robust after addressing the potential endogeneity problems. My results suggest a potential way to transfer better labor protection practices from developed to emerging markets.

Case Report: Treatment policy for female adolescents in the grip of chronic suicidality

IntroductionWithin the Dutch clinical field of specialized mental health care for youth, an increasing subgroup of female adolescents with severe chronic suicidal behavior is recognized. This group was also identified in a Dutch psychological autopsy study among 35 relatives of adolescents (aged 10–19 years old) who died by suicide. There seems to be a lack of knowledge and consensus how to treat this severe chronic suicidal behavior, resulting in stagnation of care and growing demoralization among patients, parents, and mental health care providers. The aim of this paper is to describe characteristics of the suicidal process, to identify challenges experienced in providing mental health care for this subgroup, and to formulate preliminary recommendations.MethodA case description from the psychological autopsy study and a review of the relevant literature.ResultsThe persistent suicidal threat and the resulting despair of the patient and their parents are forcing the mental health care provider into an impasse: the primary focus of treatment slowly moves to guarantee the patient's safety, which leaves the treatment of underlying problems underexposed. Due to the chronicity of the suicidal ideation and behavior in a phase in which identity formation and developing cognitive and emotional regulation skills are important developmental tasks, we identify a risk of developing a suicidal identity.DiscussionBased on expert knowledge, we make recommendations on (1) treating suicidality as a transdiagnostic phenomenon with its own meaning and function, (2) implementing treatment considerations promoting the autonomy, (3) aiming at continuity of care and prevention of repeated patient referrals by creating a multidisciplinary network of care providers, and (4) making chronic suicidality tolerable for the care provider.ConclusionWe propose preliminary practical recommendations in our quest for optimal mental health care for chronically suicidal adolescents.

Factors predicting self-care behavior of cardiovascular patients during the COVID-19 epidemic

BackgroundThe COVID-19 virus has had wide-ranging effects on all healthcare systems and a direct impact on all areas of human life in all countries around the world. Therefore, it is necessary to take preventive actions to reduce the prevalence and severity of the complications associated with this disease. The purpose of this study was to explain the dimensions of adopting general self-care behaviors (mask-wearing, social distancing, hand hygiene, and home quarantine) for preventing COVID-19 based on the theory of planned behavior (TPB) in cardiovascular patients.MethodsThis was a descriptive-analytical study conducted with the participation of 420 patients referring to health and treatment centers of Ahvaz, southwest of Iran, in 2022. Sampling was done using a non-random (convenience) method. The data collection tool was a questionnaire containing items addressing demographic characteristics, questions related to the TPB, and questions dealing with the adoption of everyday self-care behaviors against contracting COVID-19. Data were analyzed using descriptive and inferential statistical methods (prevalence, mean, standard deviation, Pearson’s correlation coefficient, and linear regression) in SPSS version 25.ResultsThe results of this study showed that the rate of adoption of self-care behaviors against COVID-19 among cardiovascular patients was moderate. The results also showed that among the constructs of the TPB, Perceived behavioral control, Subjective norms, and Perceived behavioral intention were the most important predictors of adopting self-care behaviors among cardiovascular patients with a change variance of 46%.ConclusionsThe results of the present study have implications for health and treatment policy makers as well as planners of educational and behavioral interventions aimed at promoting the adoption of self-care behaviors against COVID-19. In this respect, managing and institutionalizing desirable behaviors among cardiovascular patients could be beneficial from economic, social, and health-related aspects.

Learning optimal biomarker-guided treatment policy for chronic disorders.

Electroencephalogram (EEG) provides noninvasive measures of brain activity and is found to be valuable for the diagnosis of some chronic disorders. Specifically, pre-treatment EEG signals in the alpha and theta frequency bands have demonstrated some association with antidepressant response, which is well-known to have a low response rate. We aim to design an integrated pipeline that improves the response rate of patients with major depressive disorder by developing a treatment policy guided by the resting state pre-treatment EEG recordings and other treatment effects modifiers. First, we design an innovative automatic site-specific EEG preprocessing pipeline to extract features with stronger signals than raw data. We then estimate the conditional average treatment effect (CATE) using causal forests and use a doubly robust technique to improve efficiency in the estimation of the average treatment effect. We present evidence of heterogeneity in the treatment effect and the modifying power of the EEG features, as well as a significant average treatment effect, a result that cannot be obtained with conventional methods. Finally, we employ an efficient policy learning algorithm to learn an optimal depth-2 treatment assignment decision tree and compare its performance with Q-Learning and outcome-weighted learning via simulation studies and an application to a large multi-site, double-blind, randomized controlled clinical trial, EMBARC.

Screening for antifolate and artemisinin resistance in Plasmodium falciparumdried-blood spots from three hospitals of Eritrea.

Antimalarial drug resistance is a major challenge hampering malaria control and elimination. About three-quarters of Eritrea's population resides in the malaria-endemic western lowlands of the country. Plasmodium falciparum, the leading causative parasite species, has developed resistance to basically all antimalarials. Continued surveillance of drug resistance using genetic markers provides important molecular data for treatment policies which complements clinical studies, and strengthens control efforts. This study sought to genotype point mutations associated with P. falciparum resistance to sulfadoxine-pyrimethamine and artemisinin, in dried-blood spots from three hospitals in the western lowlands of Eritrea. Dried-blood spot samples were collected from patients visiting Adi Quala, Keren and Gash Barka Hospitals, between July and October, 2014. The patients were followed up after treatment with first line artesunate-amodiaquine, and dried-blood spots were collected on day three after treatment. Nested polymerase chain reaction and Sanger sequencing techniques were employed to genotype point mutations in the Pfdhfr (PF3D7_0417200), Pfdhps (PF3D7_0810800) and PfK13 (PF3D7_1343700) partial gene regions. Sequence data analyses of PCR-positive isolates found wild-type artemisinin haplotypes associated with resistance (Y493Y, R539R, I543I) in three isolates, whereas four mutant antifolate haplotypes associated with resistance were observed in six isolates. These included the triple-mutant Pfdhfr (S108N, C59R, N51I) haplotype, the double-mutant Pfdhfr (N51I, S108N) haplotype, the single-mutant Pfdhfr (K540E) haplotype, and the mixed-mutant Pfdhfr-Pfdhps (S108N, N51I + K540E) haplotype. Other findings observed were, a rare non-synonymous Pfdhfr V45A mutation in four isolates, and a synonymous Pfdhps R449R in one isolate. The mutant antifolate haplotypes observed indicate a likely existence of full SP resistance. Further studies can be carried out to estimate the prevalence of SP resistance. The wild-type artemisinin haplotypes observed suggest artemisinin is still an effective treatment. Continuous monitoring of point mutations associated with delayed parasite clearance in ART clinical studies is recommended.

Special issue PRO] A demonstration of estimands and sensitivity analyses for time-to-deterioration of patient reported outcomes

ABSTRACT In oncology trials, health-related quality of life (HRQoL), specifically patient-reported symptom burden and functional status, can support the interpretation of survival endpoints, such as progression-free survival. However, applying time-to-event endpoints to patient-reported outcomes (PRO) data is challenging. For example, in time-to-deterioration analyses clinical events such as disease progression are common in many settings and are often handled through censoring the patient at the time of occurrence; however, disease progression and HRQoL are often related leading to informative censoring. Special consideration to the definition of events and intercurrent events (ICEs) is necessary. In this work, we demonstrate time-to-deterioration of PRO estimands and sensitivity analyses to answer research questions using composite, hypothetical, and treatment policy strategies applied to a single endpoint of disease-related symptoms. Multiple imputation methods under both the missing-at-random and missing-not-at-random assumptions are used as sensitivity analyses of primary estimands. Hazard ratios ranged from 0.52 to 0.66 over all the estimands and sensitivity analyses modeling a robust treatment effect favoring the treatment in time to disease symptom deterioration or death. Differences in the estimands include how people who experience disease progression or discontinue the randomized treatment due to AEs are accounted for in the analysis. We use the estimand framework to define interpretable and principled approaches for different time-to-deterioration research questions and provide practical recommendations. Reporting the proportions of patient events and patient censoring by reason helps understand the mechanisms that drive the results, allowing for optimal interpretation.

Risk equations for prosthetic joint infections (PJIs) in UK: a retrospective study using the Clinical Practice Research Datalink (CPRD) AURUM and GOLD databases

BackgroundProsthetic joint infections (PJIs) are a serious negative outcome of arthroplasty with incidence of about 1%. Risk of PJI could depend on local treatment policies and guidelines; no UK-specific risk...

Does the Porter hypothesis hold in China? evidence from the “2+26” regional air pollution treatment policy

Abstract This study analyzed the impact of environmental regulation, specifically the “2+26” regional strategy for air quality improvement, on corporate research and development (R&D) investment in China. We developed a theoretical model based on the argument that R&D investment rises with regulation intensity. Using 2010–2019 data from China's listed companies located in the Beijing-Tianjin-Hebei region and its surrounding areas, we treated the $2+26$ policy as a quasi-natural experiment and adopted a difference-in-differences approach to explore its effect on firm R&D input. A positive association was observed between firm R&D intensity and the $2+26$ strategy's implementation in major polluting industries. Our results provide in-depth insights into the $2+26$ strategy's economic consequences, which are potentially of interest to both scholars and policymakers.