C. Daniel Mullins

Recommendations for Incorporating Patient-Reported Outcomes Into Clinical Comparative Effectiveness Research in Adult Oncology

Examining the patients subjective experience in prospective clinical comparative effectiveness research (CER) of oncology treatments or process interventions is essential for informing decision making. Patient-reported outcome (PRO) measures are the standard tools for directly eliciting the patient experience. There are currently no widely accepted standards for developing or implementing PRO measures in CER. Recommendations for the design and implementation of PRO measures in CER were developed via a standardized process including multistakeholder interviews, a technical working group, and public comments. Key recommendations are to include assessment of patient-reported symptoms as well as health-related quality of life in all prospective clinical CER studies in adult oncology; to identify symptoms relevant to a particular study population and context based on literature review and/or qualitative and quantitative methods; to assure that PRO measures used are valid, reliable, and sensitive in a comparable population (measures particularly recommended include EORTC QLQ-C30, FACT, MDASI, PRO-CTCAE, and PROMIS); to collect PRO data electronically whenever possible; to employ methods that minimize missing patient reports and include a plan for analyzing and reporting missing PRO data; to report the proportion of responders and cumulative distribution of responses in addition to mean changes in scores; and to publish results of PRO analyses simultaneously with other clinical outcomes. Twelve core symptoms are recommended for consideration in studies in advanced or metastatic cancers. Adherence to methodologic standards for the selection, implementation, and analysis/reporting of PRO measures will lead to an understanding of the patient experience that informs better decisions by patients, providers, regulators, and payers.

Cost-of-illness studies : a review of current methods.

The number of cost-of-illness (COI) studies has expanded considerably over time. One outcome of this growth is that the reported COI estimates are inconsistent across studies, thereby raising concerns over the validity of the estimates and methods. Several factors have been identified in the literature as reasons for the observed variation in COI estimates. To date, the variation in the methods used to calculate costs has not been examined in great detail even though the variations in methods are a major driver of variation in COI estimates. The objective of this review was to document the variation in the methodologies employed in COI studies and to highlight the benefits and limitations of these methods.The review of COI studies was implemented following a four-step procedure: (i) a structured literature search of MEDLINE, JSTOR and EconLit; (ii) a review of abstracts using pre-defined inclusion and exclusion criteria; (iii) a full-text review using pre-defined inclusion and exclusion criteria; and (iv) classification of articles according to the methods used to calculate costs. This review identified four COI estimation methods (Sum_All Medical, Sum_Diagnosis Specific, Matched Control and Regression) that were used in categorising articles. Also, six components of direct medical costs and five components of indirect/non-medical costs were identified and used in categorising articles.365 full-length articles were reflected in the current review following the structured literature search. The top five cost components were emergency room/inpatient hospital costs, outpatient physician costs, drug costs, productivity losses and laboratory costs. The dominant method, Sum_Diagnosis Specific, was a total costing approach that restricted the summation of medical expenditures to those related to a diagnosis of the disease of interest.There was considerable variation in the methods used within disease subcategories. In several disease subcategories (e.g. asthma, dementia, diabetes mellitus), all four estimation methods were represented, and in other cases (e.g. HIV/AIDS, obesity, stroke, urinary incontinence, schizophrenia), three of the four estimation methods were represented. There was also evidence to suggest that the strengths and weaknesses of each method were considered when applying a method to a specific illness. Comparisons and assessments of COI estimates should consider the method used to estimate costs both as an important source of variation in the reported COI estimates and as a marker of the reliability of the COI estimate.

Concordance between administrative claims and registry data for identifying metastasis to the bone: an exploratory analysis in prostate cancer

BackgroundTo assess concordance between Medicare claims and Surveillance, Epidemiology, and End Results (SEER) reports of incident BM among prostate cancer (PCa) patients. The prevalence and consequences of bone metastases (BM) have been examined across tumor sites using healthcare claims data however the reliability of these claims-based BM measures has not been investigated.MethodsThis retrospective cohort study utilized linked registry and claims (SEER-Medicare) data on men diagnosed with incident stage IV M1 PCa between 2005 and 2007. The SEER-based measure of incident BM was cross-tabulated with three separate Medicare claims approaches to assess concordance. Sensitivity, specificity and positive predictive value (PPV) were calculated to assess the concordance between registry- and claims-based measures.ResultsBased on 2,708 PCa patients in SEER-Medicare, there is low to moderate concordance between the SEER- and claims-based measures of incident BM. Across the three approaches, sensitivity ranged from 0.48 (0.456 – 0.504) to 0.598 (0.574 - 0.621), specificity ranged from 0.538 (0.507 - 0.569) to 0.620 (0.590 - 0.650) and PPV ranged from 0.679 (0.651 - 0.705) to 0.690 (0.665 - 0.715). A comparison of utilization patterns between SEER-based and claims-based measures suggested avenues for improving sensitivity.ConclusionClaims-based measures using BM ICD 9 coding may be insufficient to identify patients with incident BM diagnosis and should be validated against chart data to maximize their potential for population-based analyses.

Continuous Patient Engagement in Comparative Effectiveness Research

THE GOAL OF COMPARATIVE EFFECTIVENESS RESEARCH (CER) is to provide patients, their advocates and caregivers, health care professionals, federal officials, policy makers, and payers with evidence-based information to make informed health care decisions. Previously, CER studies were designed by researchers and had relatively little input from patients. Patient engagement has rapidly gained acceptance as crucial to the successful translation of CER for all interested parties. Experiences with patient engagement in research, including community-based participatory research, suggest that success hinges on patients being interested and emotionally involved in the research question and understanding their role in the CER process. Evaluation of information from the Agency for Healthcare Research and Quality and the Patient-Centered Outcomes Research Institute suggests that CER may be enhanced through continuous patient engagement. The framework for doing so, as proposed in this Viewpoint, reflects pragmatic experiences and observations in which patient engagement has helped to shape and translate CER for patients and health care professionals; however, the framework needs to be tested empirically (FIGURE). This proposed 10-step process for CER describes how patient engagement might guide CER toward patient-centered outcomes research and offers suggestions for the process and purpose of patient engagement across the 10 steps. Each step has different purposes, advantages and disadvantages, and implications for time and resources. The proposed framework is intended to span the entire “life cycle” of a CER project. At the first step, patients could help identify understudied CER topics. By soliciting input from diverse patients, the process could generate a broad array of topics, from which a more narrow focus could be achieved by framing specific research questions. When designing a potential framework for a specific CER question, patients would provide a “reality check,” indicating the extent to which the proposed framework reflects their personal experiences. When CER involves primary data collection, patient input could help determine the best practices for data collection, provide input about the proposed content of the data collection tool, and participate in pilot testing survey items. Traditionally, patient feedback is infrequently used during the development of the analysis plan. However, this framework proposes that patients could assist in helping to define or categorize variables even if they do not have training in research methods. When reviewing and interpreting results, patients could reflect on whether results are plausible and believable, what other factors should be considered, and how results may vary across subgroups of patients. In the translation phase, patients could identify which results are easy or difficult to understand. If the results do not affect patients or are counterintuitive, CER findings will not be translated into medical practice. Patients could also offer suggestions for how best to explain study findings to other patients. Patients could help determine the best dissemination strategies, provide dissemination channels, and craft specific messages targeted to patients who will benefit most. Thoughtful consideration should be given to determining which approach would best elicit the patient’s perspective at each particular step. For example, during the early stages of research, it may be most beneficial to engage patients through patient forums or telephone conversations to solicit potential topics of importance. As research progresses to protocol development, involving patients in stakeholder meetings could provide an opportunity for robust discussion regarding which outcomes to assess, populations to include, and treatment options to compare. Input on the patient experience also could be obtained from indirect means of engagement. For example, using online patient forums in which groups of patients talk about their disease may be a source of valuable information provided the process adheres to ethical standards of protection of human research participants. When creating the conceptual framework, collecting data, and specifying the analysis plan, more in-depth information and patient input may be required. Methods of engagement such as in-person meetings, focus groups, and individual patient interviews could allow patients to give more detailed input. Patients could assist in framing the message, creating plain language summaries, targeting audi-

Persistence, Switching, and Discontinuation Rates Among Patients Receiving Sertraline, Paroxetine, and Citalopram

Study Objective. To compare persistence, switching, and discontinuation rates among patients taking brand‐name selective serotonin reuptake inhibitors (SSRIs).

Risk of discontinuation of atypical antipsychotic agents in the treatment of schizophrenia

OBJECTIVES To compare discontinuation rates of atypical antipsychotic agents in patients with schizophrenia. METHOD Adult Maryland Medicaid patients with schizophrenia were categorized based on initial atypical antipsychotic drug received: aripiprazole (n=446); olanzapine (n=1705); quetiapine (n=1467); risperidone (n=1580); and ziprasidone (n=700). Discontinuation was measured using refill patterns, allowing 14-day gaps between refill dates. Using olanzapine as the reference drug, the hazard of discontinuation within the first year of follow-up was compared across atypicals using Cox proportional hazard models adjusted for demographic and clinical covariates. Sensitivity analysis tested the robustness of results by using different definitions of the index date. RESULTS At one-year follow-up, most patients discontinued their antipsychotic medication (90.4% adjusted mean discontinuation). The hazard ratio (HR) for discontinuing therapy in patients starting treatment on aripiprazole, risperidone, or ziprasidone was not significantly different from olanzapine [HR 1.047, 0.973 and 0.990, respectively]. Quetiapine was associated with significantly higher hazard of discontinuation [HR 1.130] than olanzapine. Covariates associated with significantly lower discontinuation were being male [HR 0.899], older age [HR 0.997] and being on concurrent medication when initiating therapy [HR 0.225]; having a previous hospitalization was associated with significantly higher discontinuation hazard [HR 1.276]. Results were robust in the sensitivity analysis. CONCLUSIONS Discontinuation rates were high at one-year follow-up and did not differ significantly for patients on aripiprazole, olanzapine, risperidone, or ziprasidone. The higher hazard of discontinuation associated with quetiapine when compared to olanzapine is consistent with that observed in Phase I of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE).

Effect of Age on Survival Benefit of Adjuvant Chemotherapy in Elderly Patients with Stage III Colon Cancer

OBJECTIVES: To estimate the modifying effect of age on the survival benefit associated with adjuvant chemotherapy receipt in elderly patients with a diagnosis of Stage III colon cancer.

Practice management guidelines for prophylactic antibiotic use in penetrating abdominal trauma: the EAST Practice Management Guidelines Work Group.

Fullen et al. first described the role for antibiotics in patients sustaining penetrating abdominal injuries. They retrospectively reviewed 295 patients who underwent celiotomy after sustaining penetrating abdominal wounds and categorized patients according to the timing of their first antibiotic dose: preoperative, n 5 16; intraoperative, n 5 98; and postoperative, n 5 81. The reported rate of trauma-related infections (incisional and intra-abdominal abscess) were 7%, 33%, and 30%, respectively. Individuals with colon injuries had postoperative infection rates of 11%, 57%, and 70% for each group, respectively. These rates remained constant even when the data were analyzed for additional risk factors, including the number of associated intra-abdominal organs injured, frequency of shock, and need for transfusion of blood products. The average time from hospital admission to laparotomy was the same for all three groups. Regardless of whether the observed difference was caused by the intraoperative or postoperative groups having a longer interval between injury and antibiotic administration or that the preoperative group had antibiotics circulating at the time of incision, this was the first study to suggest that the timing of antibiotic administration can impact the development of injury-related infections in patients with penetrating abdominal injuries. The importance of broad-spectrum antibiotic coverage for these patients was demonstrated by Thadepalli et al. in 1973. This study was a prospective, randomly assigned comparison of kanamycin and cephalothin to kanamycin and clindamycin. Both antibiotic combinations were administered preoperatively. The clindamycin group had a significantly lower rate of infection in the postoperative period compared with the cephalothin group (10% vs. 27%). They further demonstrated that the difference was caused by significantly more anaerobic infections in the cephalothin group (21%) compared with the clindamycin group (2%). These two studies demonstrated a significantly lower rate of infection when antibiotics providing aerobic and anaerobic coverage are administered before operative treatment. Prophylactic antibiotics for patients sustaining penetrating abdominal injuries with intestinal contamination have a role for reducing the rate of incisional wound infection subjected to gastrointestinal soiling. A single dose providing sufficient concentration within the wound during the vulnerable period is optimal. The other aspect of prophylactic antibiotic administration in trauma is the potential therapeutic role. The problem is to define the time period when contamination of the abdominal cavity becomes an established infection. At celiotomy, the intestinal wound is closed, eliminating further contamination and soiling of the peritoneal cavity. Thus, no further antibiotic should be necessary. Surgeons have concluded that “prophylactic antibiotics” in penetrating abdominal trauma can reduce the incidence of postoperative infectious complications. Since the mid-1970s, no study has included a placebo control group because of the high incidence of infectious complications after intestinal injury. However, many studies in the past 2 decades have compared various antibiotic regimens to evaluate single agents versus combination regimens, duration of administration, and, more recently, the pharmacokinetics and cost implications of single versus combination therapy.

Healthcare Rationing by Proxy

The application of cost-effectiveness analysis in healthcare has become commonplace in the US, but the validity of this approach is in jeopardy unless the proverbial

Cost-Effectiveness of Cytochrome P450 2C19 Genotype Screening for Selection of Antiplatelet Therapy with Clopidogrel or Prasugrel

US50 000 per QALY benchmark for determining value for money is updated for the 21st century.While the initial aim of this articlewas to review the arguments for abandoning the