Decisional capacity of depressed elderly to consent to electroconvulsive therapy

The purpose of this article is to determine the abilities of severely depressed elderly to consent to electroconvulsive therapy (ECT) and to investigate the impact of educational intervention on their capacity. Forty severely depressed adults referred for ECT, with Mini-Mental State Examination scores greater than 20, were recruited. Using the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), decisional capacities were assessed at baseline and reassessed after education. Between the 2 assessments, all subjects received standard education, and half of the group was subsequently randomized to receive further education. At baseline, the geriatric group scored lower on understanding, reasoning, and choice and higher on appreciation. After education, all MacCAT-T scores increased for both age groups. Depressed elderly in the sample, as a group, had adequate decisional capacities to consent to ECT. They showed greater improvement in decisional capacity with education. The findings highlight the importance of providing education to the elderly to optimize their ability to give informed consent.     

Decisional capacity for informed consent in schizophrenia research

BACKGROUND: The adequacy of subjects' informed consent to research is the focus of an important public and professional debate. The potential impairment of decisional capacity in persons with schizophrenia is central to the discussions. This study ascertains the decisional capacity for informed consent in schizophrenic research subjects, to determine if reduced capacity relates to specific aspects of psychopathologic features and to test the hypothesis that reduced capacity can be remediated with an educational informed consent process. METHODS: Decisional capacity was assessed for 30 research subjects with schizophrenia and 24 nonill (normal) comparison subjects. Measures of psychopathologic features and cognition were obtained for the subjects with schizophrenia. Subjects who performed poorly on the decisional capacity measure received an educational intervention designed to improve their ability to provide informed consent and were then retested. RESULTS: The patient group did not perform as well as the controls on initial decisional capacity assessment. Poor performance was modestly related to the extent of symptoms but robustly related to cognitive impairments. Following the educational intervention, the performance of subjects with schizophrenia was equal to that of the nonill comparison group. CONCLUSIONS: Many persons with schizophrenia may be challenged by the cognitive demands of an informed consent process for research participation. In many cases, their reduced capacity can be compensated by a more intensive educational intervention as part of the informed consent process.     

Using a brief intervention to improve decisional capacity in schizophrenia research

Studies have shown that individuals with psychiatric or general medical illness can benefit from interventions designed to enhance decisional capacity for research informed consent. In some cases, interventions have been rather lengthy or complex. The current study was designed to determine whether a brief intervention could improve decisional capacity in people with schizophrenia. Thirty individuals with schizophrenia and 30 healthy comparison participants were presented with a hypothetical research scenario. Decisional capacity was assessed with the MacArthur Competence Assessment Tool-Clinical Research version. Those with schizophrenia received a brief intervention aimed at improving understanding of the research protocol, after which decisional capacity was reassessed. A neuropsychological battery and symptom rating scales were also administered. At baseline, the schizophrenia group earned significantly lower scores than the comparison group on 2 aspects of decisional capacity (understanding, appreciation). At follow-up, the schizophrenia group had improved significantly on understanding and was no longer significantly different from the comparison group on any of the 4 dimensions of decisional capacity. Follow-up analyses also showed a significant effect of the intervention on a subset of the schizophrenia group who had performed most poorly at baseline. Participants with schizophrenia earned significantly lower scores than those in the comparison group across multiple neuropsychological domains. These findings add to the existing literature indicating that brief interventions can improve decisional capacity in individuals with schizophrenia, despite the fact that the illness typically causes significant cognitive dysfunction. The use of such interventions will enable a larger number of people with schizophrenia to make informed decisions regarding research participation.     

Capacity to provide informed consent for participation in schizophrenia and HIV research

OBJECTIVE: The degree to which people with psychiatric symptoms and cognitive dysfunction can provide informed consent to participate in research is a controversial issue. This study was designed to examine the capacity of subjects with schizophrenia and subjects with HIV to provide informed consent for research participation and to determine the relationships among cognitive dysfunction, psychiatric symptoms, and decisional capacity. METHOD: Twenty-five men and women with a DSM-IV diagnosis of schizophrenia and 25 men and women with HIV were recruited. The groups were compared in terms of neuropsychological functioning, psychiatric symptoms, and ability to provide informed consent to a hypothetical drug trial. RESULTS: Eighty percent of the subjects with schizophrenia and 96% of the HIV-positive subjects demonstrated adequate capacity to consent to the hypothetical drug trial, but subjects in the schizophrenia group had significantly lower scores on two of the four aspects of decisional capacity. For the subjects with schizophrenia, neuropsychological functioning and psychiatric symptoms (e.g., apathy and avolition), but not psychotic symptoms (e.g., hallucinations and delusions), were significantly associated with decisional capacity. CONCLUSIONS: The majority of subjects who are recruited and willing to participate in schizophrenia or HIV research will have adequate capacity to provide consent. Cognitive dysfunction and the symptoms shown to be associated with impaired decisional capacity are not unique to schizophrenia and may occur with many other forms of illness. These findings underscore the importance of considering how decisional capacity will be assessed in all types of research, regardless of the specific condition being studied.     

Informed consent in medication-free schizophrenia research

OBJECTIVE: The authors' goal was to determine whether people with schizophrenia experience changes in decisional capacity when their antipsychotic regimens are discontinued for research purposes. METHOD: Capacity for informed consent for research, neuropsychological performance, and psychiatric symptoms were assessed before and after discontinuation of antipsychotic medication in 10 individuals with schizophrenia. RESULTS: Overall, participants showed minimal change on most measures during the medication-free interval, although their reasoning ability declined significantly. All participants who demonstrated adequate understanding of study procedures at enrollment retained this capacity throughout the study. CONCLUSIONS: Participants in medication-free schizophrenia research do not show a major decline in decisional capacity. However, the apparent decline in reasoning ability found in this study is of concern and underscores the need for both additional research on this topic and the development of remediational interventions aimed at enhancing this aspect of decisional capacity.     

Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: preliminary results of a randomized trial.

BACKGROUND: Many severely depressed patients do not benefit from or tolerate existing treatments. Repetitive transcranial magnetic stimulation (rTMS) has been reported to benefit depression. We compared rTMS to electroconvulsive therapy (ECT) in severely ill, depressed patients. METHODS: Twenty-five patients with a major depression (unipolar or bipolar) deemed clinically appropriate for ECT were randomly assigned to rTMS (10-20 treatments, 10 Hz, 110% motor threshold applied to the left dorsolateral prefrontal cortex for a total of 10,000-20,000 stimulations) or a course of bitemporal ECT (4-12 treatments). The primary outcome measure was the 24-item Hamilton Depression Rating Scale (HDRS). The Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale (YMS), and Clinical Global Impression scale (CGI) were secondary measures. Minimal rescue medications were utilized. RESULTS: Mean percent improvement on the baseline HDRS score did not significantly differ between the two treatments (i.e., 55% for the rTMS group vs. 64% for the ECT group [p = ns]). With response defined as a 50% reduction from baseline and a final score < or = 8 on the HDRS, there was also no significant difference between the two groups. We did not observe any differences between groups on the secondary measures. CONCLUSIONS: A 2-4 week randomized, prospective trial comparing rTMS to ECT produced comparable therapeutic effects in severely depressed patients.     

Understanding of placebo controls among older people with schizophrenia

Research protocols frequently necessitate procedures or design elements that differ from those used in routine clinical care. An example is the inclusion of a placebo arm in many randomized clinical trials. Because there are risks to taking a placebo when one has a chronic disorder such as schizophrenia, ascertaining how well people with severe mental illness understand placebos is an important task for empirical research ethics. We investigated whether schizophrenia patients' understanding of placebo controls could be improved with a brief educational intervention. We randomized 49 middle-aged and older patients with schizophrenia or schizoaffective disorder to receive either (1) a routine explanation of placebos in the context of consent for a hypothetical double-blind placebo-controlled clinical trial, or (2) the consent for the hypothetical trial plus a brief educational module explaining placebos in more depth. Understanding of placebos was assessed with a 12-item questionnaire, and we examined demographic, clinical, neurocognitive, and decision-making correlates of understanding of placebos. Those participants who received the intervention obtained higher scores on the placebo post-test compared to those who received the standard information alone. Performance on the placebo post-test was positively correlated with measures of decisional capacity and neurocognitive abilities and negatively correlated with severity of negative symptoms, but it showed no relationship with positive or general symptoms. Some participants interpreted the common phrase "sugar pill" as relating somehow to diabetes. We conclude that the level of understanding of important research design-related information is not static but may be influenced by how investigators approach the consent process.     

A preliminary study of interactive questioning methods to assess and improve understanding of informed consent among patients with schizophrenia

Growing recognition of the inadequacy of traditional methods of providing informed consent, especially for individuals vulnerable to impaired decisional capacity, has spurred recent interest in how to assess and improve components of consent-related decision making. In this preliminary study, we aimed to compare different methods of interactive questioning during presentation of research consent information among patients with schizophrenia. Patients were randomized to receive either standard administration (SA) of a consent form or one of two interactive questioning methods: Corrective Feedback (CF), in which the correct answer was provided following the participant's response, or Errorless Learning (EL), in which correct answers were provided just prior to the question. The MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) was used to measure understanding, appreciation, reasoning, and expression of a choice following presentation of the consent form. There was no significant effect of condition (SA vs. EL vs. CF) on any of the components of decisional capacity. Understanding scores measured during the consent process were higher than those measured afterward, but the two scores were highly correlated. Thus, the results of this randomized study suggest that interactive questioning neither helped nor harmed understanding, appreciation, or reasoning among patients with schizophrenia. Other considerations, however, may favor use of such methods in the consenting process.     

Effects of stimulus intensity on the efficacy and safety of twice‐weekly,bilateral electroconvulsive therapy (ECT) combined with antipsychotics in acute mania: a randomised controlled trial

Objectives: To examine differences in speed of improvement and remission in people with mania undergoing bilateral, brief‐pulse, twice‐weekly electroconvulsive therapy (ECT) at stimulus intensities administered just above and 2.5 times their individually titrated seizure threshold. Methods: Consecutive, eligible subjects with mania, prescribed ECT, were randomised to receive treatments at stimulus doses either just above or 2.5 times their individually titrated seizure thresholds. Main outcomes were the speed of improvement and remission as measured by the Young Mania Rating Scale (YMRS) and the Clinical Global Impressions—Improvement scale (CGI‐I) and cognitive side effects assessed by the Mini‐Mental State Exam, the Wechsler Memory Scale, and a scale for autobiographical memory. Results: A total of 24/26 subjects (92.3%) given threshold ECT and 22/24 subjects (91.7%) given suprathreshold ECT were significantly improved [CGI = 2; odds ratio (OR) = 1.1, 95% confidence interval (CI): 0.1–8.4; p = 1.0] at the end of ECT. A total of 88% of the sample had remitted [YMRS < 10; threshold 23/26 (88.5%) versus suprathreshold 21/24 (87.5%)], with no significant differences between interventions (OR = 1.1, 95% CI: 0.2– 6.0; p = 1.0). The interventions did not differ significantly in the time or number of ECT treatments required for improvement or remission. Both interventions were equally safe. Conclusions: Bilateral, twice‐weekly ECT delivered at stimulus intensities just above individually titrated seizure threshold was as effective and safe as ECT administered at stimulus intensities 2.5 times seizure threshold in rapidly resolving the symptoms of acute mania.     

Achieving Equity in Informed Consent: A Culturally-Informed Perspective for the Consideration and Consent of Minority Patients for Electroconvulsive Therapy

Electroconvulsive therapy (ECT) is highly efficacious to treat severe depression in older adults. Yet, patients of ethnic and racial minorities are consistently underrepresented amongst those who receive ECT across all age groups. One strong hypothesis to explain this disparity is that minority patients are less likely to trust medical professionals and are therefore less likely to consent for ECT. Increasing participation of depressed, elderly, minority patients is uniquely challenging. Senior minority individuals have survived decades of medical and social injustices that no other demographic, specifically younger minorities or clinically-matched Caucasian peers, can truly comprehend from a first-hand perspective. This article provides a perspective based in cultural translational science to conversations of informed consent for ECT that removes our self-imposed stigma against discussing past and ongoing injustices with minority patients. Reducing disparities to geriatric minorities through equity of informed consent means that clinicians must validate the unique minority experience in medicine as it pertains to agreeing to a treatment modality as emotionally, socially, and historically laden as ECT.     

Reducing psychiatric stigma and discrimination

BACKGROUND: Across the world there are programmes challenging negative stereotypes of people with mental health problems and associated discriminatory behaviours, but the evidence base describing what works in practice is still underdeveloped. This paper evaluates the effectiveness of a mental health training intervention with the police force in England. METHOD: A total of 109 police officers attended training workshops and completed pre- and post-questionnaires detailing knowledge, attitudes and behavioural interventions. RESULTS: Mean attitude scores fell from 2.4 at baseline to 2.3 at follow-up (p < 0.0001) using a 5-point Likert scale. Five key message statements were assessed - 70 % of cases successfully reported more messages at follow-up as compared to baseline; however, the stereotype linking people with mental health problems with violent behaviour overall was not successfully challenged. Positive impacts on police work, particularly improvements in communication between officers and subjects, were reported by a third of cases. CONCLUSIONS: Short educational interventions can produce changes in participants' reported attitudes towards people with mental health problems, and can leave police officers feeling more informed and more confident to support people in mental distress.     

Coercion and informed consent in research involving prisoners

Prison-based research has been limited due to concern that prisoners may represent a vulnerable population secondary to possible coercion and limited capacity for voluntary informed consent. This study was designed to assess decisional capacity and susceptibility to coercion in prison research subjects. Subjects were 30 mentally ill prisoners and 30 healthy controls. The groups were compared on ability to provide informed consent to a hypothetical drug trial, susceptibility to possible coercion, neuropsychological functioning, and psychiatric symptoms. Results indicated that all controls and all but one of the prisoners demonstrated adequate capacity to consent to the hypothetical drug trial. However, when decisional capacity was measured quantitatively, prisoners performed significantly worse regarding two aspects of this ability. Regarding possible coercion, prisoners' main reasons for participating in research included avoiding boredom, meeting someone new, appearing cooperative in hopes of being treated better, and helping society. Neuropsychological functioning was strongly positively correlated with decisional capacity and negatively correlated with susceptibility to possible coercion, whereas psychiatric symptoms were only weakly correlated with these variables. In conclusion, a very high percentage of particularly vulnerable, mentally ill prisoners demonstrated adequate capacity to consent to research. Lower scores on a quantitative measure of decisional capacity suggest that extra care should be taken during the consent process when working with these subjects. The reasons prisoners gave for participating in our research indicated that the prison setting may have influenced their decision to participate, but that they were not actually coerced into doing so. Despite serious past incidents, ethicists will need to consider the possibility that prisoners have become an overprotected population.     

Improving understanding of research consent in middle-aged and elderly patients with psychotic disorders.

Individuals with schizophrenia may show impaired capacity to make decisions about participating in research, yet these patients also show considerable heterogeneity in decisional abilities. Problems with procedures contribute to patients' difficulties in understanding consent forms. Few studies have focused on improving comprehension of research consent in older patients with psychotic disorders. In this study, 80 middle-aged and elderly outpatients with schizophrenia or related psychotic disorders and 19 normal comparison subjects were randomized to receive a routine consent (RC) or enhanced consent (EC) procedure. The EC procedure consisted of a computerized slide show incorporating more structure and review of important information. A comprehension test was administered after the consent procedure; subjects were given up to three trials of the post-test to answer all of the questions correctly. Overall, the normal comparison subjects obtained a higher score on the post-consent comprehension test than the patients. Within each of these two groups, those who received EC had better comprehension than those who received RC. Interestingly, EC patients did not differ significantly from RC normal comparison subjects in their post-test scores. Among the patients, comprehension test scores correlated with level of education and cognitive performance.     

A new brief instrument for assessing decisional capacity for clinical research

CONTEXT: There is a critical need for practical measures for screening and documenting decisional capacity in people participating in different types of clinical research. However, there are few reliable and validated brief tools that could be used routinely to evaluate individuals' capacity to consent to a research protocol. OBJECTIVE: To describe the development, testing, and proposed use of a new practical instrument to assess decision-making capacity: the University of California, San Diego Brief Assessment of Capacity to Consent (UBACC). The UBACC is intended to help investigators identify research participants who warrant more thorough decisional capacity assessment and/or remediation efforts prior to enrollment. DESIGN, SETTING, AND PARTICIPANTS: We developed the UBACC as a 10-item scale that included questions focusing on understanding and appreciation of the information concerning a research protocol. It was developed and tested among middle-aged and older outpatients with schizophrenia and healthy comparison subjects participating in research on informed consent. In an investigation of reliability and validity, we studied 127 outpatients with schizophrenia or schizoaffective disorder and 30 healthy comparison subjects who received information about a simulated clinical drug trial. Internal consistency, interrater reliability, and concurrent (criterion) validity (including correlations with an established instrument as well as sensitivity and specificity relative to 2 potential "gold standard" criteria) were measured. MAIN OUTCOME MEASURES: Reliability and validity of the UBACC. RESULTS: The UBACC was found to have good internal consistency, interrater reliability, concurrent validity, high sensitivity, and acceptable specificity. It typically took less than 5 minutes to administer, was easy to use and reliably score, and could be used to identify subjects with questionable capacity to consent to the specific research project. CONCLUSION: The UBACC is a potentially useful instrument for screening large numbers of subjects to identify those needing more comprehensive decisional capacity assessment and/or remediation efforts.     

Influence of mood state on capacity to consent to research in patients with bipolar disorder

OBJECTIVES: Experts have debated the ability of patients with bipolar illness to consent to research participation when manic. We compared 25 euthymic bipolar and 26 manic bipolar patients in their understanding of three hypothetical studies of varying complexity. METHODS: Hypothetical studies were presented as written informed consent forms, which were reread up to three times. Questions included assessment of hypothetical study purposes, procedures, risks and benefits, and voluntariness of participation. RESULTS: After adjusting for educational level, subjects with mania had lower mean understanding scores for all three hypothetical studies compared to euthymic subjects on initial assessment. By the end of Trial 3 of each hypothetical study, there were no significant differences between groups. The proportion of subjects with mania who met predetermined pass criteria for sufficient understanding was lower than the proportion of euthymic subjects on initial assessment of the first hypothetical study, but not the other hypothetical studies (odds ratio = 0.24; 95% confidence interval = 0.07-0.8; p = 0.02). Both groups exhibited an increase in the pass proportion by the end of the third trial for each hypothetical study with no significant differences between groups. CONCLUSIONS: We conclude that subjects with mania exhibited significantly poorer levels of understanding of relevant information in hypothetical research consent forms compared to euthymic subjects when initially presented with research information. The improvement in manic patients' understanding scores with the iterative review of consent forms suggests that many manic patients may be able to consent to research protocols containing an educational intervention as a part of the informed consent process.     

Predictors of the short-term responder rate of Electroconvulsive therapy in depressive disorders - a population based study

ABSTRACT: BACKGROUND: The aim of the present study is to investigate the responder rate of Electroconvulsive therapy, ECT, in clinical routine work and to define clinical characteristics predictive of response to ECT. The main hypothesis is that the responder rate of ECT might be lower in clinical routine than in controlled trials. METHODS: This is a population-based study of all patients (N = 990) treated with ECT for depressive disorders, between 2008--2010 in eight hospitals in Sweden. Patients with Clinical Global Impression-Improvement scores of 1 or 2 (much improved) within one week after ECT were considered responders to ECT. The predictive values of single clinical variables were tested by means of chi-squared tests and the relative importance was tested in a logistic regression analysis. RESULTS: The responder rate was 80.1%. A higher proportion of older patients (>50 years) responded (84.3% vs. 74.2%, p < 0.001). Psychotically depressed patients responded better (88.9% vs. 81.5% for severely depressed and 72.8% for mildly depressed, p < 0.001). There were no significant differences in responder rates between patients suffering from bipolar, first or recurrent major depressive syndromes, or a depressive episode of schizoaffective disorder. Patients with personality disorder had a lower responder rate (66.2% vs. 81.4%, p < 0.001). Also, outpatients had a lower responder rate (66.3%) compared to inpatients (83.4%, p < 0.001). In the logistic regression analysis, inpatient status, psychotic symptoms, absence of schizoaffective disorder and older age were independent factors associated with response to ECT. CONCLUSIONS: This study focuses exclusively on the short term responder rate with ECT in clinical practice. Similarly to results from controlled trials a high responder rate is reported. Older patients, more severely ill patients, psychotically ill patients and patients without personality disorders had the highest responder rates. Inpatients may have better outcome with ECT than outpatients.     

Ethical issues in psychiatric research on children and adolescents

Psychiatric research on children and adolescents is ethically justified by the need to reduce the burden that mental illnesses place on young people, their families, and society. Such research must be conducted with careful attention to the ethical principles of beneficence, justice, and respect for persons. Child and adolescent psychiatrists who collaborate on research trials or advise patients and families about research participation should consider nine domains when evaluating the ethical acceptability of particular protocols. These domains include scientific merit and design; expertise, commitment, and integrity; risks and benefits; confidentiality; participant selection and recruitment; informed consent and decisional capacity; incentives; institution and peer/professional review; and data presentation. Special ethical issues in child and adolescent psychiatry research concern the use of randomized, controlled treatment trials; the informed consent process for research involving adolescents; the therapeutic misconception; and conflicts of interest in physician referrals.     

Magnetic and seizure thresholds before and after six electroconvulsive treatments

OBJECTIVES: Electroconvulsive therapy (ECT) is a well-established treatment in psychiatry. It has been reported that in patients with nondelusional major depression, transcranial magnetic stimulation (TMS) may substitute for ECT. To explore whether ECT and TMS share mechanisms of action, we studied the effects of ECT on both seizure threshold (ST) and magnetic motor threshold (MT). METHODS: We measured ST and MT in 10 patients referred for ECT. MT was defined as the minimal power of the TMS equipment at which a motor evoked potential (MEP) response could be detected 50% of the time. ST was defined as the minimal intensity of electrical stimulation needed to elicit an adequate seizure. ECT was performed following the methods recommended by the American Psychiatric Association. All subjects signed an informed consent for participation in the research. RESULTS: We measured MT and ST in 10 patients before and after 6 ECT treatments. No changes in MT were detected from the treatment (paired t-test: t = 1.05, SD = 4.78, p = 0.25). ST, on the other hand, increased significantly with treatment (paired t-test: t = 2.99, SD = 190.20, p < 0.001). CONCLUSIONS: ECT and TMS do not share a common mechanism at least with regard to MT and ST.     

The partners in care approach to ethics outcomes in quality improvement programs for depression

OBJECTIVE: Patient centeredness and equity are major quality goals, but little is known about how these goals are affected by efforts to improve the quality of care. The authors describe an approach to addressing these goals in a randomized trial of quality improvement for depressed primary care patients. METHODS: For four ethics goals (autonomy, distributive justice, beneficence, and avoiding harm), the authors identify intervention features, study measures, and hypotheses implemented in Partners in Care, a randomized trial of two quality improvement interventions, relative to usual care and summarize published findings pertinent to these outcomes. RESULTS: To implement an ethics framework, modifications were required in study design and in measures and analysis plans, particularly to address the autonomy and justice goals. Extra resources were needed for sample recruitment, for intervention and survey materials, and to fund an ethics coinvestigator. The interventions were associated with improvements in all four ethics areas. Patients who received the interventions were significantly more likely to receive the treatment they had indicated at baseline as their preferred treatment (autonomy goal). Intervention-associated benefits occurred more rapidly among sicker patients and extended to patients from ethnic minority groups, resulting in a reduction in ethnic-group disparities in health outcomes relative to usual care (distributive justice goal). The interventions were associated with improved quality of care and health outcomes (beneficence goal) and with reduced use of long-term minor tranquilizers (goal of avoiding harm). CONCLUSION:S: It is feasible to explicitly address ethics outcomes in quality improvement programs for depression, but substantial marginal resources may be required. Nevertheless, interventions so modified can increase a practice's ability to realize ethics goals.     

Sense and nonsense: an essay on schizophrenia research ethics

In this essay, the authors select topics from the current debate on the ethics of schizophrenia research. Accepting competent and voluntary informed consent as essential for most projects, the authors discuss the relation of diagnosis to decisional capacity, the respective roles of psychosis and cognitive impairments in decisional capacity, and whether impairments in capacity can be remediated. The roles of investigator, external agent, patient subject, and family or surrogate in the informed consent process are reviewed. A lack of understanding of the treatment of persons with schizophrenia has distorted and inflamed public discussion of issues such as 'withholding treatment'. A standard, based in common sense, is proposed: for viewing protocols; for allowing autonomy and altruism despite diagnostic class; and, for a meaningful discussion of what is meant by and what should be done about 'risk without direct benefit' protocols.