An experimental design for the development of adaptive treatment strategies

In adaptive treatment strategies, the treatment level and type is repeatedly adjusted according to ongoing individual response. Since past treatment may have delayed effects, the development of these treatment strategies is challenging. This paper advocates the use of sequential multiple assignment randomized trials in the development of adaptive treatment strategies. Both a simple ad hoc method for ascertaining sample sizes and simple analysis methods are provided.     

Up-front versus sequential randomizations for inference on adaptive treatment strategies

Adaptive treatment strategies are useful in the treatment of chronic diseases such as AIDS and cancer because they allow tailoring the treatment to a patient's need and disease status. We consider two randomization schemes for clinical trials that are commonly used to design studies comparing adaptive treatment strategies, namely, up-front randomization and sequential randomization. Up-front randomization is the classical method of randomization where patients are randomized at the beginning of the study to pre-specified treatment strategies. In sequentially randomized trials, patients are randomized sequentially to available treatment options over the duration of the therapy as they become eligible to receive subsequent treatments. We compare the efficiency and the power of the traditional up-front randomized trials with that of sequentially randomized trials designed for comparing adaptive treatment strategies based on a continuous outcome. The analytical and simulation results indicate that, when properly analyzed, sequentially randomized trials are more efficient and powerful than up-front randomized trials.     

The Use of Anecdotal Information in a Hypothetical Lung Cancer Treatment Decision

This mixed-methods study examined variables associated with use of experience-based (i.e., anecdotal) decisional strategies among 85 undergraduate students presented with 2 hypothetical lung cancer scenarios. Participants were asked to think aloud while they made their treatment choice. Eleven decisional strategies were identified and grouped into either data or experience-based strategies. Approximately, 25% of participants used experience-based strategies. Use of experience-based strategies was more likely if the participant reported involvement in the life of someone going through cancer treatment, and if they rated print-based media sources as less important. Use of experience-based strategies was associated with choosing surgery instead of radiation for lung cancer treatment.     

Economic evaluation of strategies for the control and management of influenza in Europe

We compared the cost-effectiveness of different strategies for the control and management of influenza for the elderly populations in three European countries (England and Wales, France, Germany). A "no intervention" scenario was compared with six control strategies: opportunistic vaccination (passive recruitment), comprehensive vaccination programmes (active recruitment), 4 weeks chemoprophylaxis course using neuraminidase inhibitors (NIs), 4 weeks chemoprophylaxis course using ion-channel inhibitors (ICIs), early treatment with NIs, and early treatment with ICIs. Vaccination strategies were the most cost-effective. Chemoprophylaxis strategies were highly expensive even under assumptions of optimal timing. Early treatment strategies with antivirals substantially increased demand for GP services and were more expensive than prevention through vaccination.     

Double robust estimation of optimal partially adaptive treatment strategies: An application to breast cancer treatment using hormonal therapy

Precision medicine aims to tailor treatment decisions according to patients' characteristics. G-estimation and dynamic weighted ordinary least squares are double robust methods to identify optimal adaptive treatment strategies. It is underappreciated that they require modeling all existing treatment-confounder interactions to be consistent. Identifying optimal partially adaptive treatment strategies that tailor treatments according to only a few covariates, ignoring some interactions, may be preferable in practice. Building on G-estimation and dWOLS, we propose estimators of such partially adaptive strategies and demonstrate their double robustness. We investigate these estimators in a simulation study. Using data maintained by the Centre des Maladies du Sein, we estimate a partially adaptive treatment strategy for tailoring hormonal therapy use in breast cancer patients. R software implementing our estimators is provided.     

Cost-effectiveness of competing diagnostic-therapeutic strategies for visceral leishmaniasis.

Reported are the results of a formal decision analysis which facilitated the choice of the most appropriate test-treatment strategy for visceral leishmaniasis in areas where the disease is endemic. The following strategies were compared: treatment of all suspects (strategy A); testing by means of parasitological investigation followed by treatment of positives (strategy B); two-step testing by means of the direct agglutination test (DAT) followed by treatment of patients with high titres as well as those with parasitologically confirmed borderline titres (strategy C); and DAT followed by treatment of positives (strategy D). The results for each strategy were expressed as costs in US$ per death averted. The effectiveness of strategies C and D was close to that of strategy A and far better than that of strategy B. The cost-effectiveness ratio for strategies C and D (US$ 465 per death averted) was not substantially higher than that of testing by means of parasitological investigation followed by treatment of positives (strategy B), which was the most cost-effective strategy at US$448 per death averted. At current prices of antimonial drugs, the cost of test-treatment strategies depends more on the cost of treatment than on that of testing. The use of a sensitive serological test such as the DAT is recommended as the basis of test-treatment strategies for visceral leishmaniasis in areas where the disease is endemic.     

Barriers to Treatment Adherence for Pediatric Patients With Sickle Cell Disease and Their Families

This study systematically identified adherence barriers and strategies in 31 adolescents with sickle cell disease (SCD) and 71 caregivers. Qualitative data indicated that forgetting was the primary barrier and caregiver reminders were the primary strategies identified by both caregivers and adolescents. However, adolescents reported significantly more barriers for pain management (p < .01) than their caregivers. Caregivers and adolescents seem to experience similar as well as a few unique barriers and strategies across multiple components of the SCD treatment regimen. Multidisciplinary treatment teams have the opportunity to facilitate dialogue with patients and their families about adherence barriers and strategies.     

Comparison of two azithromycin distribution strategies for controlling trachoma in Nepal

OBJECTIVE: The study compares the effectiveness of two strategies for distributing azithromycin in an area with mild-to-moderate active trachoma in Nepal. METHODS: The two strategies investigated were the use of azithromycin for 1) mass treatment of all children, or 2) targeted treatment of only those children who were found to be clinically active, as well as all members of their household. FINDINGS: Mass treatment of children was slightly more effective in terms of decreasing the prevalence of clinically active trachoma (estimated by clinical examination) and of chlamydial infection (estimated by DNA amplification tests), although neither result was statistically significant. CONCLUSION: Both strategies appeared to be effective in reducing the prevalence of clinically active trachoma and infection six months after the treatment. Antibiotic treatment reduced the prevalence of chlamydial infection more than it did the level of clinically active trachoma.     

Measurement in public health: what pulmonary tuberculosis management has taught us

Pulmonary tuberculosis rates are increasing worldwide, including in Spain. One of the main challenges when treating this disease is achieving treatment completion, since studies have shown that approximately 30-35% of all patients do not take their medications as intended. The present article explores a continuum of evaluation strategies and performance measures for assessing the effectiveness of community-based programs designed to enhance treatment completion in patients with active pulmonary tuberculosis. Four traditional evaluation strategies (case studies, retrospective and case-control studies, forecasting/modeling, and cost effectiveness analysis) and 2 emerging and promising approaches (quality of life assessment and indicators of the continuum of care) are presented. Several of the evaluation strategies reviewed indicate that treatment programs using directly observed therapy (DOT) that are comprehensive, community-based and patient-centered achieve the highest treatment completion rates. Combinations of these strategies are recommended to create a body of evidence capturing the impact and nuances of community-based public health interventions in improving health outcomes, in this case for patients with pulmonary tuberculosis.     

Selective testing for streptococcal pharyngitis in adults

Some physicians test for group A streptococcal pharyngitis in all patients who have a sore throat, while others use a variety of clinical strategies to select patients to be tested. Using published data on the accuracy of a clinical decision rule, this benefit-cost analysis compares the calculated outcomes of 21 different management strategies applied to 1,000 hypothetical adults with pharyngitis. Strategies that best accomplish one physician's treatment goals may perform poorly when evaluated in a different practice setting or using different goals. The best strategies are identified for different treatment objectives and for different assumptions about the benefits of treatment so each physician can choose a strategy consistent with his or her preferences.     

Estimation of the treatment effect in the presence of non‐compliance and missing data

Treatment non‐compliance and missing data are common problems in clinical trials. Non‐compliance is a broad term including any kind of deviation from the assigned treatment protocol, such as dose modification, treatment discontinuation or switch, often resulting in missing values. Missing values and treatment non‐compliance may bias study results. Follow‐up of all patients until the planned end of treatment period irrespective of their protocol adherence may provide useful information on the effectiveness of a study drug, taking the actual compliance into account. In this paper, we consider non‐compliance as discontinuation of treatment and assume that the endpoint of interest is recorded for some non‐complying patients after treatment discontinuation. As a result, the patient's longitudinal profile is dividable into on‐ and off‐treatment observations. Within the framework of depression trials, which usually show a considerably high amount of dropouts, we compare different analysis strategies including both on‐ and off‐treatment observations to gain insight into how the additional use of off‐treatment data may affect the trial's outcome. We compare naïve strategies, which simply ignore off‐treatment data or treat on‐ and off‐treatment data in the same way, with more complex strategies based on piecewise linear mixed models, which assume different treatment effects for on‐ and off‐treatment data. We show that naïve strategies may considerably overestimate treatment effects. Therefore, it is worthwhile to follow up as many patients as possible until the end of their planned treatment period irrespective of compliance, including all available data in an analysis that accounts for the different treatment conditions. Copyright © 2013 John Wiley & Sons, Ltd.     

Coping strategies of cancer patients in Ukraine

This case study explores the coping strategies of oncology patients and their family members in Ukraine. These coping strategies are seen as an individual‐level response to the organizational and financial failures of the Ukrainian health care system. Based on semistructured interviews with medical doctors, patients, representatives of charitable foundations, and policy makers, we identify a variety of coping strategies, including personal connections and informal payments. Unequal access to diagnostic and treatment services is observed: coping strategies are developed by patients and their families taking into account the available financial and social capital. Importantly, we could not identify a typical path for cancer patients as cancer patients act in an environment of great uncertainty—in terms of their prognosis and in terms of the cost of treatment. With a weak state and financial uncertainty, patients and physicians perceive coping strategies rather positively as it may contribute to the chance of life.     

Evaluation of argon laser treatment of diabetic retinopathy and its diffusion in The Netherlands

Argon laser treatment of diabetic retinopathy (DR) is the best evaluated case in the field of minimally invasive therapy. A well-organized randomized controlled trial was followed by formal cost-analyses and cost-effectiveness analyses. Laser treatment of DR proved to be cost-effective in a situation where there was no satisfactory treatment previously. Subsequently, screening strategies for retinopathy were developed. Systematic screening for DR in diabetic populations would be cost-saving from a societal perspective. The availability of effective and cost-effective therapy and cost-saving screening strategies for DR warrants active policy making to stimulate the implementation of strategies to control retinopathy in diabetic populations. Such strategies would ideally include both guided diffusion of argon lasers and the organization of screening programs. Data from the Netherlands are used to illustrate the diffusion of argon lasers in health care. After a slow start, argon lasers have diffused widely in the Dutch health care system. This development is complemented by recommendations for screening of the European diabetic population, which were issued in 1991. More active cooperation of all parties involved would benefit in preventing blindness from DR.     

乙肝疫苗免疫策略对乙型肝炎发病和流行的影响

目的为了探索乙肝疫苗免疫策略对乙型肝炎发病和流行的影响,进一步探索防治策略,控制乙肝的流行态势。方法采用流行病学对比分析的方法,分析国家将乙肝疫苗纳入免疫规划后不同的免疫策略对安定区乙型肝炎流行趋势的影响。结果将乙肝疫苗纳入免疫规划,特别是开展新生儿乙肝疫苗及时接种免疫策略后,安定区乙型肝炎发病率呈明显下降趋势,5岁以下儿童的乙肝感染率及发病率得到有效的控制。结论重点做好新生儿乙肝疫苗及时接种工作是控制乙肝流行最有效的途径;同时也提出了进一步加强成人乙肝疫苗免疫的问题。     

A search for strategies to engage women in substance abuse treatment

Retention is a well-documented predictor of favorable outcome of substance abuse treatment. In order to remain in treatment, clients must initially engage in the treatment process. This issue is a particular challenge for clinicians who continually seek motivational strategies that will draw each individual into the treatment process. Few engagement strategies have been specifically tested to determine their efficacy. The results of this study indicate that outpatient clients who received engagement services during the intake period showed increased use of these services, relative to a comparison group, throughout the treatment process. In addition, tangible engagement services provided to women during the intake period for outpatient substance abuse treatment had no significant effect on the rates of admission, discharge, and service utilization.     

Long-term effect of three different strategies for mass diethylcarbamazine administration in bancroftian filariasis: follow-up at 10 years after treatment

The long-term effect of three different strategies for mass diethylcarbamazine (DEC) administration in bancroftian filariasis was assessed 10 years after start of treatment in three endemic communities in Tanzania. The strategies were the standard 12 day treatment (strategy I); a semi-annual single-dose treatment (strategy II); and a monthly low-dose treatment (strategy III). Treatment was given only during the first year. Following reductions immediately after treatment, overall community microfilaraemia levels were approaching pre-treatment levels in all three communities, 10 years later. In individuals who were microfilaria-positive and treated at baseline, the treatment had a long-term effect on microfilarial intensities, with geometric mean intensities being only 11%, 13% and 2% of pre-treatment levels 10 years later for strategies I, II and III, respectively. This suppressive effect was most pronounced for strategy III, which also cleared microfilaraemia and circulating filarial antigenaemia in a larger proportion of treated individuals than the other strategies. Most of the follow-up individuals who developed microfilaraemia between 2 and 10 years after start of treatment had also been microfilaraemic before treatment, suggesting that reappearance of microfilaraemia may be due to surviving female worms and/or that previously microfilaraemic individuals have a higher chance of reinfection than previously amicrofilaraemic individuals.     

The role of epidemiology in challenging the HIV/AIDS pandemic

The HIV/AIDS pandemic has challenged the resourcefulness of epidemiology and epidemiologists. In response to the challenge, epidemiologists have used existing epidemiologic strategies, expanded existing strategies, and developed new strategies to answer key questions about the transmission of HIV, the natural history of HIV at the molecular, host, and community levels, for evaluation of treatment effectiveness and intervention strategies, and to inform public health policy. In responding to the challenge of the pandemic, epidemiologists have also increasingly collaborated with scientists from other disciplines, particularly immunology, virology, and the behavioral sciences. Examples of the application of these epidemiologic strategies are presented.     

Improving Quality of Care in Substance Abuse Treatment Using Five key Process Improvement Principles

Process and quality improvement techniques have been successfully applied in health care arenas, but efforts to institute these strategies in alcohol and drug treatment are underdeveloped. The Network for the Improvement of Addiction Treatment (NIATx) teaches participating substance abuse treatment agencies to use process improvement strategies to increase client access to, and retention in, treatment. NIATx recommends five principles to promote organizational change: (1) understand and involve the customer, (2) fix key problems, (3) pick a powerful change leader, (4) get ideas from outside the organization, and (5) use rapid cycle testing. Using case studies, supplemented with cross-agency analyses of interview data, this paper profiles participating NIATx treatment agencies that illustrate successful applications of each principle. Results suggest that organizations can successfully integrate and apply the five principles as they develop and test change strategies, improving access and retention in treatment, and agencies' financial status. Upcoming changes requiring increased provision of behavioral health care will result in greater demand for services. Treatment organizations, already struggling to meet demand and client needs, will need strategies that improve the quality of care they provide without significantly increasing costs. The five NIATx principles have potential for helping agencies achieve these goals.     

艾滋病免疫重建研究进展

越来越多的研究表明,HAART后艾滋病患者的免疫力可以恢复并能够对抗机会性感染.随着对艾滋病发病机制和免疫病理的深入研究,一些新的治疗策略和手段纷纷涌现.此文对艾滋病的主要免疫发病机制、HAART后的免疫重建、HAART面临的挑战和一些新的治疗策略进行了综述.