DOES PROFESSIONAL AUTONOMY PROTECT MEDICAL FUTILITY JUDGMENTS?

Despite substantial controversy, the use of futility judgments in medicine is quite common, and has been backed by the implementation of hospital policies and professional guidelines on medical futility. The controversy arises when health care professionals (HCPs) consider a treatment futile which patients or families believe to be worthwhile: should HCPs be free to refuse treatments in such a case, or be required to provide them? Most physicians seem convinced that professional autonomy protects them from being forced to provide treatments they judge medically futile, given the lack of patient benefit as well as the waste of medical resources involved. The argument from professional autonomy has been presented in a number of articles, but it has not been subjected to much critical scrutiny. In this paper I distinguish three versions of the argument: 1) that each physician should be free to exercise his or her own medical judgment; 2) that the medical profession as a whole may provide futility standards to govern the practice of its members; and 3) that the moral integrity of each physician serves as a limit to treatment demands. I maintain that none of these versions succeeds in overcoming the standard objection that futility determinations involve value judgments best left to the patients, their designated surrogates, or their families. Nor do resource considerations change this fact, since they should not influence the properly patient‐centered judgment about futility.     

The Futility of Futility: Death Causation is the ��Elephant in the Room�� in Discussions about Limitation of Medical Treatment

The term “futility” has been widely used in medical ethics and clinical medicine for more than twenty years now. At first glance it appears to offer a clear-cut categorical characterisation of medical treatments at the end of life, and an apparently objective way of making decisions that are seen to be emotionally painful for those close to the patient, and ethically, and also potentially legally hazardous for clinicians. It also appears to deal with causation, because omission of a futile treatment cannot surely be a cause of death. The problem is that futility can be argued to be a “false friend”, in that it gives an appearance of representing a reliable conceptual basis, in ethics, for limitation of medical treatment—usually in the context of dying—without actually doing so. In fact, the concept of futility is a conflation of clinical judgement about outcomes of treatment and the quality or even value of life, and has really failed to contribute much to the advancement of decision-making and hence care at the end-of-life. It also has the capacity to medicalise the personal space. Deliberations about the likely outcomes of medical treatment are necessary, and medical expertise is pivotal. However, futility is argued to have a better future in partnership with a broad social action agenda about the process of dying, such as that articulated in health promoting palliative care, as a basis for better “death-ways” in the 21st century (Kellehear 2005). Medicine needs to more honest and upfront about its limits, as death is, after all, the elephant in everybody's room.     

Defining Medical Futility and Improving Medical Care

It probably should not be surprising, in this time of soaring medical costs and proliferating technology, that an intense debate has arisen over the concept of medical futility. Should doctors be doing all the things they are doing? In particular, should they be attempting treatments that have little likelihood of achieving the goals of medicine? What are the goals of medicine? Can we agree when medical treatment fails to achieve such goals? What should the physician do and not do under such circumstances? Exploring these issues has forced us to revisit the doctor-patient relationship and the relationship of the medical profession to society in a most fundamental way. Medical futility has both a quantitative and qualitative component. I maintain that medical futility is the unacceptable likelihood of achieving an effect that the patient has the capacity to appreciate as a benefit. Both emphasized terms are important. A patient is neither a collection of organs nor merely an individual with desires. Rather, a patient (from the word “to suffer”) is a person who seeks the healing (meaning “to make whole”) powers of the physician. The relationship between the two is central to the healing process and the goals of medicine. Medicine today has the capacity to achieve a multitude of effects, raising and lowering blood pressure, speeding, slowing, and even removing and replacing the heart, to name but a minuscule few. But none of these effects is a benefit unless the patient has at the very least the capacity to appreciate it. Sadly, in the futility debate wherein some critics have failed or refused to define medical futility an important area of medicine has in large part been neglected, not only in treatment decisions at the bedside, but in public discussions—comfort care—the physician’s obligation to alleviate suffering, enhance well being and support the dignity of the patient in the last few days of life.     

Futility and the obligations of physicians

It is becoming increasingly common (at least in the United States) for doctors to appeal to futility judgments as the basis for certain types of clinical decisions, such as the decision to withhold CPR. The clinical use of futility judgments raises two basic questions regarding futility. First, how is the concept of futility to be understood? Secondly, once we have a clearer understanding of futility, what role should determinations of futility play in clinical decision-making? Much of the discussion about the concept of futility has centered on the value-ladenness of futility judgments. I argue that futility determinations need to be distinguished from two other types of value-based judgments, namely, identification of the goals of treatment and treatment decisions based on an assessment of the benefits and burdens of treatment. If this distinction is sound, it suggests a very limited role for futility determinations in clinical decisionmaking, a role which should serve to promote communication between doctor and patient.     

Monitoring futility and efficacy in phase II trials with Bayesian posterior distributions—A calibration approach

A multistage single arm phase II trial with binary endpoint is considered. Bayesian posterior probabilities are used to monitor futility in interim analyses and efficacy in the final analysis. For a beta‐binomial model, decision rules based on Bayesian posterior probabilities are converted to “traditional” decision rules in terms of number of responders among patients observed so far. Analytical derivations are given for the probability of stopping for futility and for the probability to declare efficacy. A workflow is presented on how to select the parameters specifying the Bayesian design, and the operating characteristics of the design are investigated. It is outlined how the presented approach can be transferred to statistical models other than the beta‐binomial model.     

Minimally Conscious States, Deep Brain Stimulation, and What is Worse than Futility

The concept of futility is sometimes regarded as a cloak for medical paternalism in that it rolls together medical and value judgments. Often, despite attempts to disambiguate the concept, that is true and it can be applied in such a way as to marginalize the real interests of a patient. I suggest we replace it with a conceptual toolkit that includes physiological futility, substantial benefit (SB), and the risk of unacceptable badness (RUB) in that these concepts allow us to articulate what is at stake in ethical judgments where outcomes are crucial in determining what should be done.     

Futility without a dichotomy: towards an ideal physician-patient relationship

The futility debate may be considered as an effort to provide a clear and justified borderline between physician and patient decision–making authority. In this paper we argue that the search for a definition of futility that provides physicians with a final argument in discussions about life–prolonging treatment, is misplaced. An acceptable and meaningful criterion of futility that satisfies this effort seems impossible. As a consequence, we reject a dichotomous domain of decision–making power as the starting point for definitions of futility. A good decision about withholding life–sustaining treatment should be justified from the perspectives of both physician and patient. In this light, a range of definitions of futility is still useful as it can clarify intuitions that a treatment is inappropriate.     

Bioethics for clinicians: 16. Dealing with demands for inappropriate treatment

Demands by Patients or their Families for treatment thought to be inappropriate by health care providers constitute an important set of moral problems in clinical practice. A variety of approaches to such cases have been described in the literature, including medical futility, standard of care and negotiation. Medical futility fails because it confounds morally distinct cases: demand for an ineffective treatment and demand for an effective treatment that supports a controversial end (e.g., permanent unconsciousness). Medical futility is not necessary in the first case and is harmful in the second. Ineffective treatment falls outside the standard of care, and thus health care workers have no obligation to provide it. Demands for treatment that supports controversial ends are difficult cases best addressed through open communication, negotiation and the use of conflict-resolution techniques. Institutions should ensure that fair and unambiguous procedures for dealing with such cases are laid out in policy statements.     

Interim analysis incorporating short‐ and long‐term binary endpoints

Designs incorporating more than one endpoint have become popular in drug development. One of such designs allows for incorporation of short‐term information in an interim analysis if the long‐term primary endpoint has not been yet observed for some of the patients. At first we consider a two‐stage design with binary endpoints allowing for futility stopping only based on conditional power under both fixed and observed effects. Design characteristics of three estimators: using primary long‐term endpoint only, short‐term endpoint only, and combining data from both are compared. For each approach, equivalent cut‐off point values for fixed and observed effect conditional power calculations can be derived resulting in the same overall power. While in trials stopping for futility the type I error rate cannot get inflated (it usually decreases), there is loss of power. In this study, we consider different scenarios, including different thresholds for conditional power, different amount of information available at the interim, different correlations and probabilities of success. We further extend the methods to adaptive designs with unblinded sample size reassessments based on conditional power with inverse normal method as the combination function. Two different futility stopping rules are considered: one based on the conditional power, and one from P‐values based on Z‐statistics of the estimators. Average sample size, probability to stop for futility and overall power of the trial are compared and the influence of the choice of weights is investigated.     

Practitioner attitudes in the United States and United Kingdom toward decisions at the end of life: are medical ethicists out of touch?

Objective To assess whether UK and US health care professionals share the views of medical ethicists about medical futility, withdrawing or withholding treatment, ordinary or extraordinary interventions, and the doctrine of double effect. Design, subjects, and setting Answers to a 138-item attitudinal questionnaire completed by 469 UK nurses studying the Open University course on “Death and Dying” were compared with those of a similar questionnaire administered to 759 US nurses and 687 US physicians taking the Hastings Center course on “Decisions Near the End of Life.” Results Practitioners accept the relevance of concepts widely disparaged by bioethicists: double effect, medical futility, and the distinctions between heroic and ordinary interventions and withholding and withdrawing treatment. Within the UK nurses'' group, the responses of a “rationalist” axis of respondents who describe themselves as having “no religion” are closer to the bioethics consensus on withholding and withdrawing treatment. Conclusions Professionals'' beliefs differ substantially from the recommendations of their professional bodies and from majority opinion in bioethics. Bioethicists should be cautious about assuming that their opinions will be readily accepted by practitioners.     

Adaptive patient enrichment designs in therapeutic trials

The utility of clinical trial designs with adaptive patient enrichment is investigated in an adequate and well‐controlled trial setting. The overall treatment effect is the weighted average of the treatment effects in the mutually exclusive subsets of the originally intended entire study population. The adaptive enrichment approaches permit assessment of treatment effect that may be applicable to specific nested patient (sub)sets due to heterogeneous patient characteristics and/or differential response to treatment, e.g. a responsive patient subset versus a lack of beneficial patient subset, in all patient (sub)sets studied. The adaptive enrichment approaches considered include three adaptive design scenarios: (i) total sample size fixed and with futility stopping, (ii) sample size adaptation and futility stopping, and (iii) sample size adaptation without futility stopping. We show that regardless of whether the treatment effect eventually assessed is applicable to the originally studied patient population or only to the nested patient subsets; it is possible to devise an adaptive enrichment approach that statistically outperforms one‐size‐fits‐all fixed design approach and the fixed design with a pre‐specified multiple test procedure. We emphasize the need of additional studies to replicate the finding of a treatment effect in an enriched patient subset. The replication studies are likely to need fewer number of patients because of an identified treatment effect size that is larger than the diluted overall effect size. The adaptive designs, when applicable, are along the line of efficiency consideration in a drug development program.     

Modeling the process of problem-solving by associative networks capable of improving the performance

In this paper a model of neural network underlying arithmetic prblem-solving is described. Memory models of procedural memory, semantic memory, and working memory, which are necessary to represent the process of the problem-solving, are constructed within a framework of a model of associative processor, HASP, proposed by one of the authors (Hirai 1983). Performance of the model has been simulated on a digital computer. By memorizing primitive knowledge of addition of two digits such as 6+8=14 in the semantic memory and procedural knowledge for the control of the process of adding in the procedural memory, the model can perform addition of multiple numbers with multiple digits. By making explicit serial associations between consecutive procedural steps, the performance of the model can be impooved, because a current procedural step primes the next one. In addition, if a preceding procedural step is a subset of the next one, merging between the two steps occurs. The performance can be improved about 20% by these priming and merging. By memorizing incorrect procedures, the model can generate four kinds of bugs of addition which were observed in children's performance.This paper is a detailed version of the talk presented in CNN'87, but the model is slightly modified     

Tricuspid annular PVCS: Radiofrequency ablation by subtricuspid retrograde catheter approach

Tricuspid annular PVCs constitute 8% of idiopathic PVCs and 5% of RV PVCs. Although a rare entity to encounter in routine clinical practice, it can be a prime culprit behind major arrhythmic burden in few individuals. Electroanatomic approach with sub tricuspid retrograde catheter technique can target those annular PVCs and decrease the arrhythmia burden to normal or near normal range. Although procedural approach for parahisian PVCs requires a close look to avoid injury to native conduction system, TA PVCs are a real challenge due to inherent catheter instability and contact issue in sub tricuspid retrograde approach.     

Evaluation of the sensitivity of a medical data-mining application to the number of elements in small databases

Data-mining methods can be used to generate rules, or identify patterns, from medical data to assist clinical diagnosis and decision-making. However, in the initial stages of a clinical study on a new diagnostic approach, there could be a limited medical dataset available; or the medical characteristics could mean that the number of patients involved in the study will never be large. Diagnoses made using the rules discovered from such small medical databases should be considered suspect unless a confidence range for a particular diagnosis can be established. A method to evaluate the sensitivity and reliability of data-mining with small databases is presented in this paper. Efron's bootstrap method for statistical testing was used to assess the accuracy of the rules produced during the training step of the data-mining algorithm. The case study for validating this new approach was based on a limited-sized mammographic database previously used to discover associations between the diagnostic features of breast masses in mammograms and the biopsy-based classification of the masses. Using the new approach, it was possible to distinguish between the association rules that were sensitive to the size of the training datasets from those that were not. The methods proposed should lead to an efficient way for validating the patterns discovered in medical data-mining applications using small datasets.     

Sequential Designs for Genetic Epidemiological Linkage or Association Studies A Review of the Literature

Objectives. The cost of a genetic linkage or association study is largely determined by the number of individuals to be recruited, phenotyped, and genotyped. The efficiency can be increased by using a sequential procedure that reduces time and cost on average. Two strategies for sequential designs in genetic epidemiological studies can be distinguished: One approach is to increase the sample size sequentially and to conduct multiple significance tests on accumulating data. If significance or futility can be assumed with a certain probability, the study is stopped. Otherwise, it is carried on to the next stage. The second approach is to conduct early linkage analyses on a coarse marker grid, and to increase marker density in later stages. Interim analyses are performed to select interesting genomic areas for follow up. The aim of this article is to give a review on sequential procedures in the context of genetic linkage and association studies. Methods. A systematic literature search was performed in the Medline and the Linkage Bibliography databases. Articles were defined as relevant if a sequential design was proposed or applied in genetic linkage or association studies. Results. The majority of proposed study designs is developed to meet the demands of specific studies and lacks a theoretical foundation. A second group of procedures is based on simulation results and principally restricted to the specific simulated situations. Finally, some theoretically founded procedures have been proposed that are discussed in detail. Conclusions. Although interesting and promising procedures have been suggested, they still lack realizations for practical purposes. In addition, further developments are required to adapt sequential strategies for optimal use in genetic epidemiological studies.     

Clinical trials and physicians as double agents.

Inherent in the dual role of physician-researcher is a conflict of interest arising out of the competing objectives of research and medical practice. Most commentary and policy recommendations on this conflict of interest have focused on the problems that arise in negotiations for informed consent. These are not, however, the only problems presented by this conflict; they are not necessarily even the most important. In order to deal with these problems, several commentators have suggested various procedural safeguards to protect the interests of the patient-subject--for example, separating the roles of physician and researcher, or introducing third parties into the relationship in order to assist in the initial or continuing negotiations for informed consent. In my view, the necessity for special procedural protections of patient-subject interests should be a discretionary judgment of the Institutional Review Board (IRB). In determining the need for special procedural protections for any research protocol, the IRB should consider three factors. To the extent that any one of these or a combination of two or more seems to present a problem, the IRB should consider it increasingly important to recommend special procedural protections: 1. There are serious impairments of the prospective subjects' capacities to consent. 2. The risk of physical or psychological injury presented by procedures done in the interests of research exceeds the threshold of "a minor increment above minimal risk." 3. The protocol is designed to introduce, test, evaluate, or compare therapeutic, diagnostic, or prophylactic maneuvers.     

Adaptive designs with arbitrary dependence structure

Adaptive designs were originally developed for independent and uniformly distributed p‐values. There are trial settings where independence is not satisfied or where it may not be possible to check whether it is satisfied. In these cases, the test statistics and p‐values of each stage may be dependent. Since the probability of a type I error for a fixed adaptive design depends on the true dependence structure between the p‐values of the stages, control of the type I error rate might be endangered if the dependence structure is not taken into account adequately. In this paper, we address the problem of controlling the type I error rate in two‐stage adaptive designs if any dependence structure between the test statistics of the stages is admitted (worst case scenario). For this purpose, we pursue a copula approach to adaptive designs. For two‐stage adaptive designs without futility stop, we derive the probability of a type I error in the worst case, that is for the most adverse dependence structure between the p‐values of the stages. Explicit analytical considerations are performed for the class of inverse normal designs. A comparison with the significance level for independent and uniformly distributed p‐values is performed. For inverse normal designs without futility stop and equally weighted stages, it turns out that correcting for the worst case is too conservative as compared to a simple Bonferroni design.     

Futility in the practice of community psychiatry

The experience of futility among frontline clinicians in community psychiatry is produced by the temporal structuring of their work. All health care providers share the disposition to intervene in the course of disease. Specific notions about the course of severe mental illness are woven into the mission of Assertive Community Treatment (ACT) as well as the treatment plan, a key paperwork tool used to stage daily activities. The treatment plan demands a narrative of progress that ACT workers often find impossible to supply. The gap between the ideal of progress and the realities of practice produce distinctive kinds of demoralization. Drawing from an ethnography of a single ACT team in the United States, this article explores how clinicians encounter, articulate, and attempt to resolve such experiences of futility. It explores their practical strategies to reframe the time horizons of work and thereby restore the sense of their own therapeutic power.