A recycling framework for the construction of Bonferroni‐based multiple tests

In this paper we describe Bonferroni‐based multiple testing procedures (MTPs) as strategies to split and recycle test mass. Here, ‘test mass’ refers to (parts of) the nominal level α at which the family‐wise error rate is controlled. Briefly, test mass is split between different null hypotheses, and whenever a null hypothesis is rejected, the part of α allocated to it may be recycled to the testing of other hypotheses. These recycling MTPs are closed testing procedures based on raw p‐values associated with testing the individual null hypotheses, and the class of such MTPs includes, for example, serial and parallel gatekeeping, fallback and Holm procedures. Graphical displays and a concise algebraic notation are provided for such MTPs. This recycling approach has pedagogical advantages and may facilitate the tailoring of MTPs for different purposes. Copyright © 2009 John Wiley & Sons, Ltd.     

Mixture-based gatekeeping procedures in adaptive clinical trials

ABSTRACT

Clinical trials with data-driven decision rules often pursue multiple clinical objectives such as the evaluation of several endpoints or several doses of an experimental treatment. These complex analysis strategies give rise to “multivariate” multiplicity problems with several components or sources of multiplicity. A general framework for defining gatekeeping procedures in clinical trials with adaptive multistage designs is proposed in this paper. The mixture method is applied to build a gatekeeping procedure at each stage and inferences at each decision point (interim or final analysis) are performed using the combination function approach. An advantage of utilizing the mixture method is that it enables powerful gatekeeping procedures applicable to a broad class of settings with complex logical relationships among the hypotheses of interest. Further, the combination function approach supports flexible data-driven decisions such as a decision to increase the sample size or remove a treatment arm. The paper concludes with a clinical trial example that illustrates the methodology by applying it to develop an adaptive two-stage design with a mixture-based gatekeeping procedure.     

Advanced multiplicity adjustment methods in clinical trials

During the last decade, many novel approaches for addressing multiplicity problems arising in clinical trials have been introduced in the literature. These approaches provide great flexibility in addressing given clinical trial objectives and yet maintain strong control of the familywise error rate. In this tutorial article, we review multiple testing strategies that are related to the following: (a) recycling local significance levels to test hierarchically ordered hypotheses; (b) adapting the significance level for testing a hypothesis to the findings of testing previous hypotheses within a given test sequence, also in view of certain consistency requirements; (c) grouping hypotheses into hierarchical families of hypotheses along with recycling the significance level between those families; and (d) graphical methods that permit repeated recycling of the significance level. These four different methodologies are related to each other, and we point out some connections as we describe and illustrate them. By contrasting the main features of these approaches, our objective is to help practicing statisticians to select an appropriate method for their applications. In this regard, we discuss how to apply some of these strategies to clinical trial settings and provide algorithms to calculate critical values and adjusted p‐values for their use in practice. The methods are illustrated with several numerical examples. Copyright © 2013 John Wiley & Sons, Ltd.     

Adverse Outcomes of Managed Care Gatekeeping

Objectives : To determine whether telephone preauthorization for reimbursement of ED care (medical “gate-keeping”) by managed care organizations (MCOs) is associated with adverse outcomes. Methods : A structured review was performed of case reports solicited during 1994 and 1995 with possible adverse outcomes related to managed care gatekeeping. Gatekeeping was defined as the requirement imposed by an MCO that ED staff contact on-call gatekeepers (i.e., clinical or nonclinical MCO personnel) to request preauthorization for ED treatment (a requirement that such MCOs enforce by refusing payment for the ED care unless preauthorization is obtained). Cases in which gatekeeper denial of preauthorization occurred were sought. Two physicians agreed on patient eligibility and classification criteria, then independently, retrospectively classified case reports identified as MCO ED payment denials into 1 of 4 categories: 1) adverse outcome; 2) patient placed at increased risk of death or disability; 3) “near miss” (emergency physicians prevented adverse outcome by caring for patient despite denial); and 4) none of the above. Results : Of the 143 cases reviewed, 29 reports represented MCO ED payment denial. Of these 29 eligible cases, there were 4 (14%) patients with adverse outcomes, 4 (14%) patients placed at increased risk, and 21 (72%) near misses. All of the 29 cases came from different EDs, representing 9 different states, with the majority from California. Adverse outcomes included respiratory failure from fulminant meningococcemia, hypovolemic syncope from ruptured ectopic pregnancy, hypovolemic arrest from vascular fibroid hemorrhage necessitating emergency hysterectomy, and prolonged postoperative course following ruptured duodenal ulcer. Patients placed at increased risk were diagnosed as having epiglottitis, myocardial infarction, ruptured ectopic pregnancy, and delayed treatment of hip septic arthritis. Near misses included diagnoses of ectopic pregnancy (n = 2), pneumothorax (n = 2), alcohol withdrawal seizures and pancreatitis necessitating intensive care unit admission, appendicitis, bacterial meningitis, cerebrovascular accident, cryptococcal meningitis in immuno-compromised host, endocarditis, incarcerated inguinal hernia, meningococcemia, meningococcal meningitis, peritonsillar abscess, pneumococcal meningitis, ruptured abdominal aortic aneurysm, shock from gastrointestinal bleeding, small bowel obstruction, schizophrenic crisis resulting in psychiatric hospitalization, suicidal depression resulting in psychiatric hospitalization, and unstable angina. Conclusion : Adverse outcomes occur with MCO gatekeeping. Although the present study cannot ascertain whether this is a frequent event or a rare one, the safety of MCO gatekeeping deserves further study.     

Economic efficiency of gate-keeping compared with fee for service plans: a Swiss example

STUDY OBJECTIVE: The impact of isolated gate-keeping on health care costs remains unclear. The aim of this study was to assess to what extent lower costs in a gate-keeping plan compared with a fee for service plan were attributable to more efficient resource management, or explained by risk selection. DESIGN: Year 2000 costs to the Swiss statutory sick funds and potentially relevant covariates were assessed retrospectively from beneficiaries participating in an observational study, their primary care physicians, and insurance companies. To adjust for case mix, two-part regression models of health care costs were fitted, consisting of logistic models of any costs occurring, and of generalised linear models of the amount of costs in persons with non-zero costs. Complementary data sources were used to identify selection effects. SETTING: A gate-keeping plan introduced in 1997 and a fee for service plan, in Aarau, Switzerland. PARTICIPANTS: Of each plan, 905 randomly selected adult beneficiaries were invited. The overall participation rate was 39%, but was unevenly distributed between plans. MAIN RESULTS: The characteristics of gate-keeping and fee for service beneficiaries were largely similar. Unadjusted total costs per person were Sw fr 231 (8%) lower in the gate-keeping group. After multivariate adjustment, the estimated cost savings achieved by replacing fee for service based health insurance with gate-keeping in the source population amounted to Sw fr 403-517 (15%-19%) per person. Some selection effects were detected but did not substantially influence this result. An impact of non-detected selection effects cannot be ruled out. CONCLUSIONS: This study hints at substantial cost savings through gate-keeping that are not attributable to mere risk selection.     

“On the doctor's orders”: A pilot study of the effects of website marketing for medical specialist providers under gatekeeping arrangements

ABSTRACT

Websites from medical specialist providers are becoming increasingly marketing oriented, but there exists a paucity of empirical research on the effects. This experimental study explored effects of exposure to real websites from medical specialist providers among Dutch adults under physician gatekeeper arrangements. Exposure led to a stronger intention to seek treatment from the specialist provider and motivation to rely on the providers’ claims. Weaker to absent effects were found for intention to question the physician gatekeeper’s referral and this was chiefly motivated by the belief that “the doctor knows best.” Implications for specialist provider marketing under gatekeeping arrangements are discussed.     

Changing Mental Health Gatekeeping: Effects on Performance Indicators

This study evaluated how a change in gatekeeping model at a health maintenance organization affected performance indicators for specialty outpatient mental health care. Gatekeeping in one division changed from in-person evaluations to a call center with routine authorization for the first eight visits. Using 1996–1999 claims data (including 2 years pre- and 2 years postintervention), the study compared performance indicator results in the affected division and another where the model did not change. Subjects included 122,751 continuously enrolled persons. Dependent variables were mental health emergency room use, treatment initiation, treatment engagement, and family treatment for child patients. After controlling for secular trends at the other division and enrollee characteristics, the division that changed gatekeeping experienced no significant impact on most indicators and an increase in family treatment for children. The move to call-center gatekeeping did not appear to have a negative impact on treatment process as reflected in these indicators.