Use of Bayesian decision analysis to maximize value in patient-centered randomized clinical trials in Parkinson's disease.

A fixed one-sided significance level of 5% is commonly used to interpret the statistical significance of randomized clinical trial (RCT) outcomes. While it is necessary to reduce the false positive rate, the threshold used could be chosen quantitatively and transparently to specifically reflect patient preferences regarding benefit-risk tradeoffs as well as other considerations. How can patient preferences be explicitly incorporated into RCTs in Parkinson's disease (PD), and what is the impact on statistical thresholds for device approval? In this analysis, we apply Bayesian decision analysis (BDA) to PD patient preference scores elicited from survey data. BDA allows us to choose a sample size (n) and significance level (α) that maximizes the overall expected value to patients of a balanced two-arm fixed-sample RCT, where the expected value is computed under both null and alternative hypotheses. For PD patients who had previously received deep brain stimulation (DBS) treatment, the BDA-optimal significance levels fell between 4.0% and 10.0%, similar to or greater than the traditional value of 5%. Conversely, for patients who had never received DBS, the optimal significance level ranged from 0.2% to 4.4%. In both of these populations, the optimal significance level increased with the severity of the patients' cognitive and motor function symptoms. By explicitly incorporating patient preferences into clinical trial designs and the regulatory decision-making process, BDA provides a quantitative and transparent approach to combine clinical and statistical significance. For PD patients who have never received DBS treatment, a 5% significance threshold may not be conservative enough to reflect their risk-aversion level. However, this study shows that patients who previously received DBS treatment present a higher tolerance to accept therapeutic risks in exchange for improved efficacy which is reflected in a higher statistical threshold.

Patient-Centered Identification of Meaningful Regulatory Endpoints for Medical Devices to Treat Parkinson's Disease.

Introduction. A growing literature has developed on identifying outcomes that matter to patients. This study demonstrates an approach involving patient and regulatory perspectives to identify outcomes that are meaningful in the context of medical devices for Parkinson's disease (PD). Methods. A systematic process was used for specifying relevant regulatory endpoints by synthesizing inputs of various sources and stakeholders. First, a literature review was conducted to identify important benefits, risks, and other considerations for medical devices to treat PD; patient discussion groups (n = 6) were conducted to refine the list of considerations, followed by a survey (n = 29) to prioritize them; and patient and Food and Drug Administration (FDA) reviewers informed specification of the final endpoints. Two FDA clinicians gave clinical and regulatory perspectives at each step. Results. Movement symptoms were ranked as most important (ranked 1 or 2 by 72% of participants) and psychological and cognitive symptoms as the next most important (ranked 1 or 2 by 52% of participants). Within movement symptoms, falls, impaired movement, bradykinesia, resting tremor, stiffness, and rigidity were ranked highly. Overall, nine attributes were identified and prioritized as patient-centric for use in clinical trial design and quantitative patient preference studies. These attributes were benefits and risks related to therapeutics for PD as well as other considerations, including time until a medical device is available for patient use. Discussion. This prospective approach identified meaningful and relevant benefits, risks, and other considerations that may be used for clinical trial design and quantitative patient preference studies. Although PD was the focus of this study, the approach can be used to study patient perspectives about other disease or treatment areas.

Parkinson's Patients' Tolerance for Risk and Willingness to Wait for Potential Benefits of Novel Neurostimulation Devices: A Patient-Centered Threshold Technique Study.

Background. Parkinson's disease (PD) is neurodegenerative, causing motor, cognitive, psychological, somatic, and autonomic symptoms. Understanding PD patients' preferences for novel neurostimulation devices may help ensure that devices are delivered in a timely manner with the appropriate level of evidence. Our objective was to elicit preferences and willingness-to-wait for novel neurostimulation devices among PD patients to inform a model of optimal trial design. Methods. We developed and administered a survey to PD patients to quantify the maximum levels of risks that patients would accept to achieve potential benefits of a neurostimulation device. Threshold technique was used to quantify patients' risk thresholds for new or worsening depression or anxiety, brain bleed, or death in exchange for improvements in "on-time," motor symptoms, pain, cognition, and pill burden. The survey elicited patients' willingness to wait to receive treatment benefit. Patients were recruited through Fox Insight, an online PD observational study. Results. A total of 2740 patients were included and a majority were White (94.6%) and had a 4-year college degree (69.8%). Risk thresholds increased as benefits increased. Threshold for depression or anxiety was substantially higher than threshold for brain bleed or death. Patient age, ambulation, and prior neurostimulation experience influenced risk tolerance. Patients were willing to wait an average of 4 to 13 years for devices that provide different levels of benefit. Conclusions. PD patients are willing to accept substantial risks to improve symptoms. Preferences are heterogeneous and depend on treatment benefit and patient characteristics. The results of this study may be useful in informing review of device applications and other regulatory decisions and will be input into a model of optimal trial design for neurostimulation devices.

A Framework for Incorporating Patient Preferences Regarding Benefits and Risks into Regulatory Assessment of Medical Technologies.

BACKGROUND: In response to 2012 guidance in which the US Food and Drug Administration's (FDA) Center for Devices and Radiological Health (CDRH) stated the importance of patient-centric measures in regulatory benefit-risk assessments, the Medical Device Innovation Consortium (MDIC) initiated a project. The project was used to develop a framework to help the Food and Drug Administration (FDA) and industry sponsors understand how patient preferences regarding benefit and risk might be integrated into the review of innovative medical devices. METHODS: A public-private partnership of experts from medical device industry, government, academia and non-profits collaborated on development of the MDIC patient centered benefit-risk framework. RESULTS: The MDIC Framework examines what patient preference information is and the potential use and value of patient preference information in the regulatory process and across the product development life cycle. The MDIC Framework also includes a catalog of patient preference assessment methods and an agenda for future research to advance the field. CONCLUSIONS: This article discusses key concepts in patient preference assessment of particular importance for regulators and researchers that are addressed in the MDIC Framework for patient centered benefit-risk assessment as well as the unique public-private collaboration that led its development.

Improving the quality of physician communication with rapid-throughput analysis and report cards.

OBJECTIVE: Problems with clinician-patient communication negatively impact newborn screening, genetics, and all of healthcare. Training programs teach communication, but educational methods are not feasible for entire populations of clinicians. To address this healthcare quality gap, we developed a Communication Quality Assurance intervention. METHODS: Child health providers volunteered for a randomized controlled trial of assessment and a report card. Participants provided telephone counseling to a standardized parent regarding a newborn screening result showing heterozygous status for cystic fibrosis or sickle cell disease. Our rapid-throughput timeline allows individualized feedback within a week. Two encounters were recorded (baseline and after a random sample received the report card) and abstracted for four groups of communication quality indicators. RESULTS: 92 participants finished both counseling encounters within our rapid-throughput time limits. Participants randomized to receive the report card improved communication behaviors more than controls, including request for teach-back (p<0.01), opening behaviors (p=0.01), anticipate/validate emotion (p<0.001) and the ratio of explained to unexplained jargon words (p<0.03). CONCLUSION: The rapid-throughput report card is effective at improving specific communication behaviors. PRACTICE IMPLICATIONS: Communication can be taught, but this project shows how healthcare organizations can assure communication quality everywhere. Further implementation could improve newborn screening, genetics, and healthcare in general.

Frequency of high-quality communication behaviors used by primary care providers of heterozygous infants after newborn screening.

OBJECTIVE: To examine the quality of communication likely to be experienced by parents when being first informed about how newborn screening identified heterozygous "carrier" status for cystic fibrosis or sickle cell disease. METHODS: Primary care providers (PCPs) of infants found to have carrier status were telephoned over a 48-month period, and asked to rehearse with a standardized patient how they would inform the infants' parent(s). 214 rehearsal transcripts were abstracted using explicit criteria methods to measure the frequency of five categories of high-quality communication behaviors. RESULTS: Overall, PCPs used large amounts of jargon and failed to use high quality communication behaviors. On average, PCPs used 18.6 total jargon words (8.7 unique words), but explained 2.4 jargon words. The most frequent assessment of understanding was the close-ended version, although it was only seen in 129 of 214 transcripts. The most common organizing behavior was importance emphasis (121/214). Precautionary empathy was rare; the most frequent behavior was "instruction about emotion" (33/214). CONCLUSION: The limited use of high-quality communication behaviors in rehearsals raises concern about parental understanding, decision-making, and psychosocial outcomes after newborn screening. PRACTICE IMPLICATIONS: Measurement of specific behaviors may help PCPs to improve communication, and thereby improve the patient experience.

Use of social support during communication about sickle cell carrier status.

OBJECTIVE: To examine the use of social support behaviors by primary care providers during delivery of positive newborn screening results for Sickle Cell Anemia carrier status. METHODS: Transcripts from 125 primary care providers who conveyed Sickle Cell Anemia carrier status to standardized parents were content analyzed using categories derived from Cutrona and Suhr's social support taxonomy. Frequencies and cross-tabulation matrices were calculated to study providers' social support utilization. RESULTS: Results showed most primary care providers (80%) incorporate social support behaviors into delivery of Sickle Cell Anemia carrier results and most frequently employed social network (61.6%) and informational support (38.4%) behaviors. Providers used tangible aid (8%), esteem (1.6%), and emotional support (9.6%) behaviors less frequently. CONCLUSION: Cutrona and Suhr's taxonomy may be a useful tool for assessing supportive communication during the delivery of Sickle Cell Anemia carrier status and could be incorporated into population scale assessments of communication quality assurance. PRACTICE IMPLICATIONS: Primary care providers may need training in how to adapt supportive behaviors to parents' needs during communication of Sickle Cell Anemia carrier status. They also may benefit from specific training about how to use esteem and emotional support.

Child health providers' precautionary discussion of emotions during communication about results of newborn genetic screening.

OBJECTIVE: To demonstrate a quantitative abstraction method for Communication Quality Assurance projects to assess physicians' communication about hidden emotions after newborn genetic screening. DESIGN: Communication quality indicator analysis. SETTING: Standardized parent encounters performed in practicing physicians' clinics or during educational workshops for residents. PARTICIPANTS: Fifty-nine pediatrics residents, 53 pediatricians, and 31 family physicians. INTERVENTION: Participants were asked to counsel standardized parents about a screening result; counseling was recorded, transcribed, and parsed into statements (each with 1 subject and 1 predicate). Pairs of abstractors independently compared statements with a data dictionary containing explicit-criteria definitions. OUTCOME MEASURES: Four groups of "precautionary empathy" behaviors (assessment of emotion, anticipation/validation of emotion, instruction about emotion, and caution about future emotion), with definitions developed for both "definite" and "partial" instances. RESULTS: Only 38 of 143 transcripts (26.6%) met definite criteria for at least 1 of the precautionary empathy behaviors. When partial criteria were counted, this number increased to 80 of 143 transcripts (55.9%). The most common type of precautionary empathy was the "instruction about emotion" behavior (eg, "don't be worried"), which may sometimes be leading or premature. CONCLUSIONS: Precautionary empathy behaviors were rare in this analysis. Further study is needed, but this study should raise concerns about the quality of communication services after newborn screening.

A qualitative secondary evaluation of statewide follow-up interviews for abnormal newborn screening results for cystic fibrosis and sickle cell hemoglobinopathy.

PURPOSE: The purpose of this qualitative analysis was to assess parental acceptability of large-scale, telephone follow-up regarding their infants' newborn screening (NBS) results, indicating carrier status for sickle cell hemoglobinopathy (SCH) and cystic fibrosis (CF). METHODS: Analysis of 195 interview transcripts focused on parents' responses to two open-ended questions: "What was your reaction to being called by me?" and "What do you think of the state NBS program having follow-up people calling parents like you?" Responses were coded using conventional content analysis procedures, and nonparametric tests were performed to analyze quantitative data. RESULTS: Most parents reported favorable opinions about the follow-up. Favorable opinions were associated with several emotional reactions to receiving follow-up (P <0.001) and three reasons why parents found the interview beneficial (P < 0.05): it provided information, clarified NBS results, and answered questions. Seventeen parents of SCH carriers reportedly had not been told their infant's NBS results and received them for the first time during the follow-up interview. CONCLUSION: Parents of CF and SCH carrier infants had favorable opinions and identified specific benefits to receiving follow-up contact. This analysis demonstrates an information deficit among carrier parents and illustrates the importance of NBS follow-up and need for comprehensive communication and counseling.

A method to assess the organizing behaviors used in physicians' counseling of standardized parents after newborn genetic screening.

Well-organized conversation can improve people's ability to comprehend and retain information. As part of a long-term effort to adapt Quality Improvement techniques for communication, we developed an explicit-criteria method to assess usage of three organizing behaviors (OBs): 'opening behaviors' to establish goals; 'structuring behaviors' to guide patients through conversation; and 'emphasizing behaviors' that signal a need for attention. Pairs of abstractors independently reviewed transcripts in a demonstration sample of conversations between physicians and standardized parents after newborn screening identifies carrier status for sickle cell disease. Criteria for at least one OB were identified in 50/84 transcripts (60%), including 27 with at least one opening behavior (32%), 5 with at least one structuring behavior (6%), and 38 with at least one emphasizing behavior (45%). The limited number of OBs raises concern about communication after newborn screening. Assessment and improvement of OB usage may improve understanding and allow parents to more actively participate in health care.

Effort required to contact primary care providers after newborn screening identifies sickle cell trait.

People with heterozygous status for sickle cell disease (also called sickle cell trait) are essentially healthy, but evidence of rare health problems has increased interest in screening adolescents and young adults prior to enlisting in athletics or military service. Ironically, almost everyone with sickle cell trait is already identified during routine newborn screening for sickle cell disease, but this identification may never reach the parents. As part of a larger statewide study of communication after newborn screening, we decided to document the amount of labor required to connect sickle cell trait screening results with primary care providers (PCPs). Case review methods examined records and call logs from the first 150 cases in a 42-month project. Our study procedures identified PCPs for 136 of 150 infants (90.6%); a total of 266 phone calls were needed. We identified 9 categories of experiences, ranging from incorrect baby names to restrictions on accepting Medicaid patients. Cases demonstrate that it is possible to connect with most PCPs after newborn screening despite warnings about difficulties with this population. Success was due to persistence, relationships with clinics and hospitals, and Internet search capabilities. If sickle cell trait identification is necessary to protect health, then only modest increases in effort will be needed to reduce disparities in service.

Improving communication between doctors and parents after newborn screening.

BACKGROUND: Newborn screening (NBS) enables early treatment, and some consider it a natural vehicle for genetic screening. Bioethicists argue for caution since families of infants with carrier status can develop psychosocial complications. This paper describes the methods and feasibility of Wisconsin's statewide project for quality improvement of communication and psychosocial outcomes after NBS. METHODS: When NBS identifies carrier status for cystic fibrosis or sickle cell, we contact primary care providers (PCPs), answer questions, and invite them to rehearse informing the parents. Three months later, we telephone the parents, assess knowledge and psychosocial outcomes, provide counseling, and assist with self-referral to further resources. Afterward, evaluation surveys are provided to the parents, to be returned anonymously. RESULTS: Birthing facilities provided accurate PCP names for 73% of 817 infants meeting inclusion criteria; we identified PCPs for 21% more. We reached 47.3% of PCPs in time to invite a rehearsal; 60% of these accepted. We successfully called 50.2% of eligible parents; 61% recalled a PCP explanation, and 48.5% evaluated the explanation favorably. Evaluations by parents with limited health literacy were less favorable. CONCLUSION: It is feasible to follow parents for psychosocial outcomes after NBS. Preliminary data about communication is mixed, but further data will describe psychosocial outcomes and investigate outcomes' associations with communication.

The relationship between nurses' religiosity and willingness to let patients control the conversation about end-of-life care.

OBJECTIVE: The study attempts to examine the relationship between nurses' religious beliefs and how nurses communicate with patients. METHOD: An online census survey was administered to graduate students in the School of Nursing at a Midwestern university. The survey was designed to measure: relational control, as measured by the subscales of dominance and task orientation in Burgoon and Hale's scale of relational communication; clinician empathy, as measured by the Jefferson scale of clinician empathy; and intrinsic and extrinsic religiosity, whether religious views are held for deep personal reasons or social reasons, as measured by the Maltby and Lewis scale. Data were analyzed using multiple regressions and one-way ANOVAs. RESULTS: Intrinsic religiosity and empathy were both associated with the willingness to relinquish relational control in certain, specific contexts, such as end-of-life care. CONCLUSION: Nurses who scored higher on a scale of intrinsic religious beliefs were more willing to let patients take control of conversations about end-of-life care. PRACTICE IMPLICATIONS: A nurse's religious beliefs can enhance the clinical experience without the nurse trying to impose his or her beliefs on the patient, as the nurse works to make sure the patient's religious beliefs are upheld.

A method to quantify and compare clinicians' assessments of patient understanding during counseling of standardized patients.

OBJECTIVE: To introduce a method for quantifying clinicians' use of assessment of understanding (AU) questions, and to examine medicine residents' AU usage during counseling of standardized patients about prostate or breast cancer screening. METHODS: Explicit-criteria abstraction was done on 86 transcripts, using a data dictionary for 4 AU types. We also developed a procedure for estimating the "load" of informational content for which the clinician has not yet assessed understanding. RESULTS: Duplicate abstraction revealed reliability kappa=0.96. Definite criteria for at least one AU were found in 68/86 transcripts (79%). Of these, 2 transcripts contained a request for a teach-back ("what is your understanding of this?"), 2 contained an open-ended AU, 46 (54%) contained only a close-ended AU, and 18 (21%) only contained an "OK?" question. The load calculation identified long stretches of conversation without an AU. CONCLUSION: Many residents' transcripts lacked AUs, and included AUs were often ineffectively phrased or inefficiently timed. Many patients may not understand clinicians, and many clinicians may be unaware of patients' confusion. PRACTICE IMPLICATIONS: Effective AU usage is important enough to be encouraged by training programs and targeted by population-scale quality improvement programs. This quantitative method should be useful in population-scale measurement of AU usage.

Breaking the silence surrounding hepatitis C by promoting self-efficacy: hepatitis C public service announcements.

Hepatitis C virus (HCV) is the most common chronic bloodborne virus in the United States. Despite this fact, there is a startling lack of awareness about HCV among individuals who might have contracted the virus. In this study, grounded in self-efficacy theory, we analyze public service announcements for HCV. Using focus groups to contextualize the responses of individuals living with HCV, we conclude that stigma and structural barriers pose the greatest challenges for health communicators trying to reach at-risk populations. The findings suggest that expanded use of celebrity appeals, realistic drug-use portrayals, more extensive use of social networking in tandem with nontraditional media, tapping into veterans, and maximizing self-efficacy messages while minimizing fear tactics offer new hope for successful health communication strategies. With 3.9 million people in the United States infected with HCV, this study offers urgently needed communication strategies to address this silent epidemic.

Pediatric residents' use of jargon during counseling about newborn genetic screening results.

OBJECTIVE: The goal was to investigate pediatric residents' usage of jargon during discussions about positive newborn screening test results. METHODS: An explicit-criteria abstraction procedure was used to identify jargon usage and explanations in transcripts of encounters between residents and standardized parents of a fictitious infant found to carry cystic fibrosis or sickle cell hemoglobinopathy. Residents were recruited from a series of educational workshops on how to inform parents about positive newborn screening test results. The time lag from jargon words to explanations was measured by using "statements," each of which contained 1 subject and 1 predicate. RESULTS: Duplicate abstraction revealed reliability kappa of 0.92. The average number of unique jargon words per transcript was 20; the total jargon count was 72.3 words. There was an average of 7.5 jargon explanations per transcript, but the explained/total jargon ratio was only 0.17. When jargon was explained, the average time lag from the first usage to the explanation was 8.2 statements. CONCLUSION: The large number of jargon words and the small number of explanations suggest that physicians' counseling about newborn screening may be too complex for some parents.

A method to quantify residents' jargon use during counseling of standardized patients about cancer screening.

BACKGROUND: Jargon is a barrier to effective patient-physician communication, especially when health literacy is low or the topic is complicated. Jargon is addressed by medical schools and residency programs, but reducing jargon usage by the many physicians already in practice may require the population-scale methods used in Quality Improvement. OBJECTIVE: To assess the amount of jargon used and explained during discussions about prostate or breast cancer screening. Effective communication is recommended before screening for prostate or breast cancer because of the large number of false-positive results and the possible complications from evaluation or treatment. PARTICIPANTS: Primary care internal medicine residents. MEASUREMENTS: Transcripts of 86 conversations between residents and standardized patients were abstracted using an explicit-criteria data dictionary. Time lag from jargon words to explanations was measured using "statements," each of which contains one subject and one predicate. RESULTS: Duplicate abstraction revealed reliability kappa = 0.92. The average number of unique jargon words per transcript was 19.6 (SD = 6.1); the total jargon count was 53.6 (SD = 27.2). There was an average of 4.5 jargon-explanations per transcript (SD = 2.3). The ratio of explained to total jargon was 0.15. When jargon was explained, the average time lag from the first usage to the explanation was 8.4 statements (SD = 13.4). CONCLUSIONS: The large number of jargon words and low number of explanations suggest that many patients may not understand counseling about cancer screening tests. Educational programs and faculty development courses should continue to discourage jargon usage. The methods presented here may be useful for feedback and quality improvement efforts.