Blockchain Papers

Mehdi Benchoufi, Raphaël Porcher, Philippe Ravaud

<ns4:p>Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing the collection of patients’ informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we will built a consent workflow using a rising technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient’s consent collection using Blockchain; thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each revision of the protocol, consent was sought again. We obtained a single document, in a standard open format, that accounted for the whole consent collection process: timestamped consent status with regards to each version of the protocol. This document cannot be corrupted, and can be checked on any dedicated public website. It should be considered as a robust proof of data. However, in a live clinical trial, the authentication system should be strengthened in order to remove the need for third parties, here the trial stakeholders, and give participative control to the peer-to-peer users. In the future, we think that the complex data flow of a clinical trial can be tracked using Blockchain, that a blockchain core functionality, named Smart Contract, could help prevent clinical trial events not to happen in the right chronological order: for example including patients before they consented or analysing case report forms data before freezing the database. Globally, we think Blockchain will help with reliability, security, and transparency, and could be a consistent step towards reproducibility.</ns4:p>

A. B. Ackerman, Anne B. Chang, Nadia Diakun-Thibault, Luca Forni · 7 authors

The President’s Precision Medicine Initiative (PMI) is “enabling a new era of clinical care through research, technology, and policies that empower patients, researchers, and providers to work together toward the development of individualized care”. Its commitment to privacy and security in the setting of responsible data sharing and transparency is articulated in the “Privacy and Trust Principles” and the “Data Security Policy Principles and Framework”, developed by an interagency working groups including the Office of the National Coordinator for Health Information Technology in conjunction with multiple stakeholders. In this paper, we review the threats to the security, confidentiality, integrity, and availability of PMI data. PMI organizations can mitigate these challenges through a new system architecture in development at MIT -- the OPAL/Enigma project -- which creates a peer-to-peer network that enables parties to jointly store and analyze data with complete privacy, based on highly optimized version of multi-party computation with a secret-sharing. An auditable, tamper-proof distributed ledger (a permissioned blockchain) records and controls access through smart contracts and digital identities. We conclude with an initial use case of OPAL/Enigma that could empower precision medicine clinical trials and research. MIT’s OPAL/Enigma challenges traditional data security paradigms. Centralized databases cannot assure security and data integrity, regardless de-identification and controlled access requirements. Safe, vetted queries that are distributed to private, encrypted databases assure that organizations and participants can share health care data with cryptographic guarantees of privacy with various stakeholders, assuring momentum for a new era of medical research and practice.

Greg Irving, John Holden

<ns4:p>Trust in scientific research is diminished by evidence that data are being manipulated. Outcome switching, data dredging and selective publication are some of the problems that undermine the integrity of published research. Methods for using blockchain to provide proof of pre-specified endpoints in clinical trial protocols were first reported by Carlisle. We wished to empirically test such an approach using a clinical trial protocol where outcome switching has previously been reported. Here we confirm the use of blockchain as a low cost, independently verifiable method to audit and confirm the reliability of scientific studies.</ns4:p>

Jim Vaught, Akin Abayomi, Tim Peakman, Peter H. Watson · 6 authors

Biobanking for clinical or research purposes includes the collection, processing, storage, and analysis of biological specimens. It is now well recognized that biobanking involves a complex array of technical and ethical/regulatory considerations. Biobanking policies and procedures are often documented by best practices that are usually voluntary but may be supplemented and reinforced by strict rules and regulations that govern informed consent, privacy, QC, and other critical issues. As biobanking has emerged as a global endeavor, with national networks and international collaboration becoming the norm, it has become even more critical that practices are coordinated and that quality standards are developed. Biobanking is also often a business endeavor, in that formal strategic and business plans need to be developed to ensure the long-term survival of the associated research programs. As new technologies are developed for using biospecimens to diagnose and treat disease, as well as to evaluate genetic risks, patients are becoming more aware of the importance and benefits of biobanking as part of the medical infrastructure. As a result, patients who donate biospecimens are becoming more interested in learning more about their own sample's use and in seeing the actual results of the research. One of the aspects of these evolving attitudes toward biobanking was addressed in a previous Q&A concerning biospecimen “ownership” in the January 2011 issue of Clinical Chemistry (Gronowski et al.; Clin Chem 57:540–4). From the broad array of issues that could be addressed, this Q&A focuses on a few critical issues that many biobanks are facing today: quality management, biobank network design, long-term sustainability, conveying the importance of biobanking to the public, and the return of research results to biospecimen donors. Five experts who are engaged in national and international biobanking programs discuss these complex issues here. What are some of the important issues related to quality management in sample collection, processing, and storage? Tim Peakman: Biobanks should aim to collect and store samples and associated data in the form most useful for scientific research. This means that they should represent the biological environment at the time of collection as closely as possible, and the introduction of variation through the way they are collected and processed should be avoided as much as possible. Where cases and controls come from different sources, this problem may be particularly acute (with the exception of purely genetic studies). In studies where samples are shipped to a different location for processing, the time delay between collection and stabilization may lead to loss of some unstable markers. Where samples are processed at local sites, maintenance of consistent intersite processing can be challenging. Odds ratios for many exposures are typically 1.2–1.5, so that introduction of uncontrolled or unmeasured variation may lead to weak associations' being overlooked, spurious associations' being further investigated, or significantly greater cost as sample size is increased to enhance power of the study. For many studies the greatest source of variation is at the preanalytical stage, in other words the collection, transport, and processing before stabilization at low temperature or on matrices such as blood spot cards. This can be managed by the implementation of a proper quality program that aims to make the collection and processing of samples as consistent as possible. Formal quality schemes such as ISO 9001:2008 may be suitable for larger studies, but whether a formal accreditation is obtained or a laboratory-based approach is taken, the quality management process should include full documentation of the sample processing trail (including dates, times, temperatures, location, operator, etc.), use of standard operating procedures (SOPs),7 training, audits, critical materials review, and so on. Practical steps to reduce introduced variability can be taken that aim to ensure the time from collection from the volunteer to stabilization is as consistent as possible across all samples and any preprocessing (such as clotting time for serum tubes) is standardized. Finally, quality of sample annotation should be ensured using approaches such as bar codes that maintain accuracy of sample attribution and avoid the risk of misidentification that can result in false positives. It is also important to empirically determine the stability of the samples under the particular collection protocol and whether this is sufficient for the intended purpose. Many analytes are quite stable in blood if they are transported and processed at 4 °C and, with a few exceptions, those analytes that aren't stable only degrade a small amount over 24 h. Establishing systems and processes to avoid this marginal loss may be expensive and unnecessary. Peter Watson and Lise Matzke: Quality management (QM) is an essential component of operating and maintaining a biobank. At the end of the day, it's “garbage-in, garbage-out,” or so they say. Operationally, biobanks must be able to track each biospecimen that is collected, processed, stored, and distributed from the facility to manage biospecimen quality and ensure effective future use. Quality is managed by an established system that verifies biospecimens are handled appropriately. Such quality systems involve the creation and maintenance of accurate process protocols, SOPs, and the activities that verify these protocols' being followed by biobank personnel (staff education and training). Further, standards and best practices set by international organizations such as the International Society for Biological and Environmental Repositories and the National Cancer Institute set guidance around the issues, provide a reference point for content of this documentation, and facilitate harmonization by national organizations and down to individual projects. Implementation of QM activities requires dedicated time and a resourcing strategy which can be very costly. Therefore the scope and scale of the program should be dictated by the scope and scale of the biobank and the nature of the research it is intended to support. A biobank supporting basic discovery research may choose a primary QM focus different from that chosen by a biobank that is intended to support multicenter validation studies. Adequate training and education of biobank personnel and a tracking mechanism to ensure training is current and role specific are essential parts of the overall QM strategy. This helps to ensure consistent and informed application of both quality assurance and QC measures. The process of review of a QM system allows for evaluation around what is and what is not working in the QM and the ability to make changes. There are several types of external assurance programs that are offered on the international stage that are complementary strategies to raise the standards across the discipline of biobanking. Some define an upper standard and use an external assessment process and measurement of product quality, while the focus for other programs is to define a minimal standard and concentrate on education. An example of the latter approach, which ties all these components of QM together, is the concept of biobank certification, which is broadly applicable for all entities handling biospecimens and is offered by the Canadian Tumour Tissue Repository and UBC Biobank Resource Centre. Helen Moore: Quality can mean very different things to different people. One might think of quality management as the process followed to determine that, in the end, you got what you set out to get. For biobanking, quality management would follow the complex set of procedures undertaken to enroll a research participant in biobanking and collect, process, annotate, and store biospecimens, and determine whether that process yielded biospecimens and associated data sufficient for the purpose collected. Foundational elements would include well-documented SOPs that are understood and accepted by those who are collecting, processing, and storing biospecimens, as well as training on SOPs and annotation of deviations from SOPs. Quality criteria must be set at the outset and suitable metrics and analytical tests used to evaluate the processes and determine whether the quality criteria have been met. Having a quality management plan in place for biobanking does not mean that perfection is expected; in fact, it is important that quality management be reasonable in scope and that errors be expected. For example, some level of biospecimen degradation may be unavoidable in some circumstances. Awareness of this possibility and being able to measure relative degradation is part of the quality management plan. Good quality management in biobanking at best can translate to higher quality and reproducibility of research results using the biospecimens. Akin Abayomi: In Africa, where extreme ambient temperatures are the order of the day in conjunction with potentially large geographical distances that samples may need to travel, attention to detail is critical. Clear and comprehensible SOPs and frequent training activities, particularly at sample acquisition research sites, are key to ensuring sample integrity. The emphasis is shifting towards minimizing preanalytical variables, which necessitates the need to have the capacity to bring the process of stabilizing the physiology of the sample closer to the donor. This is possible with good logistics and strategic team activity dovetailing with synchronized operations between the researchers and the biobanking teams. Communication is critical in this process. Kit development and dispatch to sites of collection with good training and harmonized operational activity all along the route of the sample until it gets to its final storage site are mandatory in this process. Where cell-line creation is part of the menu of operations, then the sooner the blood mononuclear cells are isolated and either frozen or processed the better the outcome. This process can start at the collection site to stabilize the cells and completed at a central facility. Staffing at peripheral collection sites will need to be upskilled and infrastructure adapted to this objective. Use of emerging room temperature storage and transportation technology to stabilize the whole sample at time of collection or soon after isolation of nucleic acids may be useful options in some environments. What are the advantages and disadvantages of centralized vs individual/local biobanks? Tim Peakman: There is no right or wrong answer to whether a study should adopt centralized or local sample processing and archiving. This will depend upon factors such as size of the study, daily volunteer recruitment rates and sample acquisition, sample processing throughput, complexity of the processing protocols, available budget, and the expertise of the study team. As a general rule, once studies reach a certain size and certain sample accrual rate, centralized biobanking offers a number of advantages but this does depend upon the study. Use of automation allows much higher numbers of samples to be processed on a daily basis much more consistently and with a robust, secure anonymized data trail. Quality data are recorded as part of the process and, if sample storage and retrieval are automated, samples can be stored and retrieved quickly from very stable, low-temperature environments with complete accuracy. Balanced against this, central services cost a lot to establish and maintain and often samples need to be shipped from collection centers that introduce delays in processing (although the effects of this can be largely mitigated using temperature-controlled shipping conditions) and increase transport costs significantly. Smaller single-site studies may benefit from local processing which is as quick as possible (and is therefore likely to preserve as many analytes as possible), is suitable for very complex protocols, and doesn't incur high setup or transport costs. This approach is limited to relatively small numbers of and can with process and variability the and requires maintenance of a data trail for studies with recruitment From that the cost sample for large studies is also increased with local need to the and of each for their study in their with an of the stability of the samples they are and processing and the costs of different Peter of At the biobanks are the of a complex activity biobanking, and some components of biobanking need increased to reduce research that of and biospecimen while need more to quality processing and and other components need both of networks can be centralized in but with distributed from and at the level are many quality, and factors that what is a facing organizations and research whether to or their A of these and the many and have often been to of the by the to in research is an essential and but of around infrastructure is The types of biobanks and research to be are other important is no only important considerations. as around issues such as reproducibility in research and the need for increased scale and quality in biobanks can only come with implementation of and the need for more components and of many types of biobanks Helen Moore: biobanks can advantages of increased of biospecimens, with systems for quality management, data management, and or local biobanks may provide advantages in and One way of these is biobanks so that individual biobanks use the or at and approaches to biobanking, the of biospecimens across different sites in a or biobank. An quality management program across the system would be an important of such a network and would include to different collection sites and a of collection and storage that might be in place at different It would be important to where approaches and processes could be at different sites, and for (and such where they could A network would good and education about the of the to answer such are to What is the of the is harmonization of approaches and quality management important to the final facilitate better biospecimens and better research through this Akin Abayomi: In Africa, where infrastructure is and can be through is an with a more central biobanks with effective to peripheral collection processing sites would the of the research team and ensure samples are as to that of the volunteer as possible. This would and The centralized more to the emerging of and biobanking being more to the of and able to to samples before of scale can be with and on of or This approach also to the of researchers biobanking which can have on and sample that are becoming more now and for future of biological The ability to focus more on good with to collaboration between studies and larger size studies, which are use of biospecimens for and studies. What are some of the issues facing biobanks in of long-term Peter Watson and Lise Matzke: Biobanks are expensive to and From collection of biospecimens to processing, storage, and activities, the of activities in a biobank is a biobanks are the biobanks in their and Further, as a research biobanks a complex and that is with biobank Biobank is therefore a of and usually the the importance of other aspects or should not be biobanks are often as not being secure they on or it is the complexity and variation of and that is the most important of this and it is the metrics to evaluate the relative importance of individual biobanks and the importance of biobanks other of research infrastructure that the critical of research are and all focus on the of research should in biobanks if the scope and need are not the for any and is very and not and the research to biobanking is recognized as an important part of particularly in the research their in to the research and then to a is At the end, the to to a set of the and standards by which biobanks should be able to at to ensure research quality, is the greatest to of individual The good is that these issues are now a part of an in the biobanking the of new strategies to these issues. Helen Moore: are often collected for specific research the research have been the research may be the biospecimens may have for research use. to the of biospecimen and the to support their storage and can be challenging. A greater emphasis on to the about the of biobanks in and to about the of biobanking, will be important to in biobanking. is about the actual costs of biobanking. The National Cancer Institute is a on the aspects of biobanking. The data will be in and in an that will be able to for about the costs associated with biobanking. Akin Abayomi: In environments with a of in and for the greatest for or is in and on to provide that can either as or as a strategy. Biobanking is not high on the and in environments its return in of and of a is not research that biobanking strategies have the of in to their research In such external can be used as to which will as a for the need to establish national and the right environment to the biobanking, and national research can biobanks better their to researchers and the Peter Watson and Lise Matzke: the of a biobank requires the biobank to be on and and key other words the of the For the the and to key is to researchers and the will the that is in biospecimen for while to the the emphasis is on the end biobanks are working for better these requires a different strategy from vs scientific to each in the design, and of a biobank. Helen Moore: Biobanks are an essential of the medical research and the for and in biobanks must be upon and It is important for the to that of research biospecimens, as well as the by biobanks of the biospecimens for current and future is to medical that may benefit the research and their In the the concept of for the good is to or who are for their they are to whether they would be to donate in the of an It is important now to the about of biospecimens for research. Such education must be across and Akin Abayomi: Communication in the of has to the and of national to and and to the from which samples will be requires a different strategy and of to the in The greatest will be from the of the and are important to effective and The in at the different can be quite and should not be For the national the importance of the is to bring to the advantages to be through not in of of its but also the of the benefits of biobanks requires the the of are critical in an strategy and form an important of overall An aware and informed is to but with this the evolving of The engaged is more and requires to on the emerging and role of biobanks in the return of research results to biospecimen and the that will result from review of and by Peter The issue of of research has become of the most and issues facing research and research in are in of data and the scale and of research data as by the in the of data from biospecimens. The complexity and of different are and the of of the and of biobanks that in between the and the research of the has an all an important issue and is often in the research by its nature and must be and to some from clinical There are both and to to this research biobanks not the clinical and should be to the for return of research is not the as an to raise issues or in the process of return of results from research and become to the biobank. Helen Moore: In larger and larger of research have become part of medical and technologies for and an important role in biospecimens. Such as well as established analysis approaches such as review, can some results that are as to the research In some cases the are of no or clinical but in other cases the may have clinical be such if in a research a clinical to be and researchers or biobanks not to be for the to research their as more is about and studies are for medical the between research and clinical are The of researchers and to return is a of much are the of what are and the benefits and of the to the research their Akin Abayomi: This is a complex clinical that will closer to the of as the concept of more of an It is to potentially useful from a or the the are and the ability to and data in an to the donors. The concept of will as a more to as and to patients more through on or or emerging issues that you will have on the future of biobanking. Tim Peakman: One of the for biobanks will be data This is likely to come from from use of the studies data and samples to other researchers and typically this involves the return of research data to the biobank once the is The of this is that it the for future of the of scientific that can be using these and the technologies used to biobanks will need to data data quality, and data are stored and in a data large biobanks are their expertise and to to large data on their sample For example, Biobank is the is about in the and of the whole and is an approach to collect data on people. data are very large and and of storage, and use. both from such as genetic and new analytical approaches and from by will be a data management in the of the of large biobanks is the of studies can use the should be taken to avoid using the of in a way that in the data It was on this basis that Biobank to the with the that in or it will be to the of all of the people. This a of the so that the can be used for other types of emerging are approaches for the and Helen Moore: across biobanks and research programs will be very important in the future of medical research to better individual in of disease, and to such data while the of individual research is a for the A better of biospecimen the effects of different biospecimen collection, processing, and storage on the of biospecimens, is need to attention to now so that can biospecimen practices for different analysis also need to be the by which biospecimens are and storing this with the biospecimens in This approach will be even more important in the future so that will be some assurance that collected and stored biospecimens are suitable or for for research and of specific as analysis technologies Akin Abayomi: will become an important of the future as a means of tracking samples and related can ensure the ability to track samples from to and to the use of in the should be able to a biological from a research site to primary or and the benefit that is in to a This will become particularly important with the use of cell-line technology in of both a quality assurance and a means of tracking and It will also as a means to in the scientific process and start the for on a standard operating quality

Mark J. Cherry

Since action for itself requires a particular content and a determinate end, whereas duty in the abstract contains nothing of the kind, the question arises: what is duty? For this definition [Bestimmung], all that is available so far is this: to do right, and to promote welfare, one’s own welfare and welfare in its universal determination, the welfare of others. (Hegel, 1991 [1821], 161, §134) Nothing in particular follows from general concepts of the right, the good, the just, or the virtuous; not even in bioethics. Even to sort useful information from noise, one must first specify a moral context within which to make decisions. Without particular content, morality cannot provide definitive guidance for choosing among different accounts of human flourishing or the proper ranking of virtues, much less how to proceed when the right and the good conflict.1 If morality is to be more than a mere formalism—for example, the empty repetition of rhetorical phrases, such as “respect patient autonomy” or “preserve human dignity”—then particular content must be specified to orient proper decision making.2 Among the challenges is that medicine is an applied science as well as a social endeavor. Medical science and the treatment of patients are always set within particular cultures and human interests. Consequently, the actual practice of health care involves an overlapping set of communities (scientific, moral, religious, and political) striving to understand and to manipulate the world in ways that humans find socially useful, morally appropriate, aesthetically pleasing, or otherwise fitting. As a result, medical reality and the expectations of clinical judgment are inevitably historically and culturally conditioned. In turn, such taken for granted background conditions impact our appreciation of moral obligations. This issue of The Journal of Medicine and Philosophy brings together three clusters of essays, focused in turn on research ethics, clinical ethics, and moral theory. Despite the array of topics, each author carefully explores core questions of bioethics: Which moral standard? Whose account of moral obligations ought to guide health care as both a theoretical and a practical endeavor? The first cluster of articles explores moral standards for guiding medical research. In medicine, one must abandon the assumption that accepted treatments are good simply because they are accepted. Instead, one must critically examine the standard of care together with new and innovative alternatives. Thorough scientific research together with robust scholarly debate is integral to reigning in the untutored human desire to ameliorate pain and suffering so that treatments do more benefit than harm. Moreover, it is difficult to know truly in medicine. Problems such as spontaneous remission and natural cures, physician remembrance of therapeutic triumphs more clearly than failures, the psychology of discovery, and the placebo effect distort judgments of a treatment’s effectiveness. At times and in various ways, patients, physicians, and scientists see what they anticipate. Medicine adds to these challenges the all too human urge to help those in need. Yet, as the history of medicine pays witness, many interventions do more harm than benefit. Human suffering caused by ill-founded but well meaning treatments has been significant. As Gelfand (2013), Meyerson (2013), and Potts et al. (2013) each make clear, rigorous scientific research and open scholarly debate are central to the advancement of medical practice and the protection of patients. Gelfand and Meyerson document, for example, the way in which clinical research with human subjects often involves a conflict between judgments regarding the proper treatment of patients and appropriate methods for obtaining good scientific data. Physicians who are both researchers and clinicians have competing professional interests, for example. The primary goal of clinicians is generally doing what is best for one’s patients within certain constraints, such as informed consent, the standard of care, and resource availability. Clinicians recommend treatments and interventions based on what they believe is in the best interests of particular patients. The primary goal of researchers, however, is the discovery of data to address research questions. The objective in a scientific inquiry is to follow an approved protocol to obtain data, to test research hypotheses or theoretical constructions, and to contribute to the base of scientific knowledge. Researchers are, however, constrained in how they may use subjects who may or may not benefit from the study design. Particular moral standards, such as “clinical equipoise,” the “precautionary principle,” and prohibitions against lying, are routinely identified as essential for fulfilling our duties to protect patients from unethical researcher conduct. Consider, for example, “clinical equipoise” which requires that clinician-researchers terminate a study when accumulated evidence so thoroughly supports one treatment arm that “the committee of investigators believe no open-minded clinician informed of the results would still favor” the other treatments being tested (Freedman, 1987, 145; cited in Gelfand, 2013, 593). Is clinical equipoise an adequate guide to appropriate ethical research on human subjects? Gelfand concludes that clinical equipoise is both morally and conceptually problematic. Morally, the difficulty is that clinical equipoise, if taken seriously, requires shutting down too many well-structured randomized clinical trials as unethical. Conceptually, the challenge lies in attempting to flesh out the ambiguous “open-minded clinician” standard. Although there is some disagreement concerning who should determine whether clinical equipoise exists, I will assume, as do most others, that this determination should be made by the physician-researcher conducting the randomized clinical trial. Presumably, the physician-researcher should begin this process by attributing knowledge of preliminary studies to these clinicians. In addition, she would have to assume that clinicians in her clinical community were aware of the general facts/theories/beliefs relevant to the clinical trial. Put differently, whether one will conclude that clinical equipoise exists depends, among other things, on what beliefs one attributes to members of the clinical community. (Gelfand, 2013, 594–95) Gelfand rightly notes that it is a very common psychological phenomenon to conclude that those who disagree with you “. . . are wrong or unaware of all the relevant facts or for some reason misunderstand the issue. Many of us often assume that if others truly understood the issues, they would agree with us” (2013, 595). Clinical equipoise, he argues, assumes that all “properly open-minded” clinicians who are informed regarding the research data would share the same background information, beliefs, standards for evaluation, and interpretation of results, as well as clinical or research goals. Having reasoned in such a fashion, however, once the physician-researcher conducting the trial concludes that clinical equipoise does not exist, he may terminate important clinical trials before adequate data can be collected. Researchers who disagree with such a conclusion may be easily ruled out as failing to be properly “open minded.” The “precautionary principle” raises related challenges. As with other human endeavors, medicine can become infatuated with the seemingly original and progressive. That technological or surgical innovations are new, however, guarantees neither superiority nor safety. The underlying rationale of the precautionary principle is to treat unproven scientific innovation with appropriate regulatory caution. When there is good reason to conclude that an innovation may cause serious harm, even though uncertainty exists regarding the probability or level of risk, the precautionary principle holds that regulatory action should proceed as if such innovation is in fact dangerous. Meyerson argues that the core difficulty with the precautionary principle is that it is unduly vague. Again, there is a need for the specification of a particular standard. All choices involve risk. How much risk and of what sort is morally acceptable? Taken too weakly, the precautionary principle offers almost no guidance: “. . . if all that is meant by the precautionary principle is that the absence of scientific certainty does not necessarily justify the refusal to regulate risky new technologies, then it is hard to see what is supposed to be distinctive about the guidance it offers” (Meyerson, 2013, 610). On the other hand, understood in a very strong manner, the principle rules out beneficial innovation: “At its strongest, the precautionary principle insists that potential benefits should be foregone unless it can be shown that they pose no risk at all. This is obviously an unacceptable position” (Sunstein, 2005; Meyerson, 2013, 610). Seeking to clarify a more moderate approach, Meyerson argues that there should be a general presumption in favor of restricting innovative technologies when they appear to pose a serious risk of harm. Proponents of the new technology, she concludes, bear the burden of proof to demonstrate the utility and relative safety of the innovation. Applied to the example of innovative surgical techniques, Meyerson argues that such a moderate approach helps to avoid the dangers that occur when surgeons are prone to bias in favor of new innovations, especially when they have a financial stake in the use of the invention, while also permitting advocates to demonstrate the safety and effectiveness of new technology. Discerning readers might at this point wish to raise the following questions: What are the risks of a bias in favor of the status quo? How should we assess the dangers of delaying innovation?3 What if, for example, scientific debate is stifled so as to preserve the status quo? In this issue, Potts et al. (2013) explore just such key concerns. For example, should researchers self censure scientific results that might undermine public confidence in medical judgment, such as the diagnosis of brain death? And, should professional journals refuse to publish articles that call into question current medical orthodoxy on such matters? Recent debate has brought brain-oriented criteria for determining death and donation after cardiac death policies into public scrutiny (see, e.g., Bernat, 2010; Iltis and Cherry, 2010; Khushf, 2010; Miller, Truog, and Brock, 2010; Shewmon, 2010; and Veatch, 2010). Some proponents of organ transplantation have argued that responsible scholarship requires refusing to publish any such results. As Potts et al. summarize: Some articles call for a closing of the debate over the criteria for death since such criteria are related to organ donation, and an ongoing debate about death criteria may negatively affect the public’s willingness to donate. They suggest allowing only ‘responsible scholarship’ in the area (according to which ‘irresponsible scholarship’ is considered to be critiquing brain-based criteria for death. . . . (2013, 626) Such debate, critics argue, creates unnecessary doubt among members of the public regarding the certainty of brain-oriented determinations of death and, consequently, for the appropriateness of procuring organs from donors who have been declared dead based on such criteria. To further complicate matters, institutional policy for determining that brain-based criteria for death has been satisfied may vary among institutions. Potts and his colleagues argue that without sustained and open debate, the harms caused by adherence to the status quo may never be adequately exposed. Is it morally appropriate to stifle or otherwise censor open-minded and scientific debate so as to further one’s preferred social goal, such as greater access to organ transplantation (or, perhaps, ever more government action on so-called human-caused global warming)? The next brace of essays turn the discussion to moral duties in clinical ethics. Mills (2013) and Reed (2013) focus on elements of procreative liberty, Stoyles and Costreie (2013) rethink voluntary euthanasia, whereas Cohen and Shapiro explore whether placebo treatment violates moral prohibitions against lying. To begin, Mills argues that reproductive liberty ought to be appreciated as a positive entitlement: “that is, a freedom to make oneself according to various ethical and aesthetic principles or values” (2013, 639). Mills contends that Michel Faucult’s analysis of the “practice of liberty” together with a naturalistic approach to rights entails at least limited positive claim rights in support of reproductive autonomy, “. . . one that requires that reproductive projects are promoted rather than simply honored, for example” (2013, 655). Reed in turn shifts our attention to an exploration of Plan B “emergency” contraception. Reed’s conceptual geography maps the moral location of emergency contraceptive pills relative to the ongoing abortion debates. He argues, for example, that “If we know that there are no postfertilization effects, then emergency contraception becomes morally similar to barrier methods: it prevents pregnancy without interfering with a fertilized egg” (2013, 670). However, insofar as Plan B contraception has a postimplantation effect, resulting in the abortion of a fetus, then abortion is an intended consequence of emergency contraception. As a result, abortion would not rightly be described as an unintended side effect of taking Plan B contraception; utilizing emergency contraception would be morally similar to other forms of early abortion. How should we appreciate reproductive liberty? And, which moral context applies to such choices? Sometimes to gain insight into the proper standards for clinical ethics, we must learn to see moral debates from new perspectives. The next two essays seek to reframe the bioethical debates regarding euthanasia and patient deception in terms of the “patient’s interests.” Stoyles and Costreie (2013) hold that the euthanasia debate has gone astray by emphasizing the importance of such distinctions as voluntary, involuntary, and nonvoluntary euthanasia. The question, they believe, is whether the practice of euthanasia accords with the “patient’s interests.” Insofar as euthanasia advances a patient’s interests, it ought to be appreciated as morally permissible. Similarly, Cohen and Shapiro conclude that while lying to patients is, all things considered, morally wrong, placebos are permissible precisely when they advance the patient’s interests in ways comparable to other forms of therapy. For example: Placebo analgesia refers to the reduction in pain following the administration of an otherwise inert substance, e.g., administering a starch pill (that does not directly alter pain physiology), which is believed by the subject to be an analgesic drug. The administration of a placebo is not inert, however, and its effects far from imaginary. Most strikingly, various findings show that placebo analgesia can under certain conditions mimic the actions of opiates on the opioidergic system, the most potent pain reducing system of the body. (2013, 699) An undue focus on deception, they argue, inappropriately skews the moral analysis. Insofar, as placebo treatment has an appropriate therapeutic effect comparable to other forms of therapy, it should not be morally ruled out. In each case, the authors challenge the reader’s perspective on such bioethical questions so as to assist us to see our moral duties anew. The final two essays take a conceptual step back from applied ethics, actively to engage moral theory. Sjöstrand et al. (2013) argue that preserving the value of patient autonomy may require medical paternalism, whereas Pamental (2013) explores the utility of pragmatism as a moral theory to guide bioethical decision making. On the one hand, Sjöstrand et al. (2013) hold that there are good reasons to support patient autonomy and to promote autonomy as a value in healthcare decision making. As a practical matter, however, sometimes weak forms of paternalism ought to be accepted to promote patient autonomy over the long term. Theoretical clarity regarding autonomy as a value is necessary, they argue, if we are to determine how best to respond to patient choices that appear to limit autonomy. If only capacity is valuable, paternalism is easily justified as soon as a patient acts or decides in a way that threatens her future autonomy. It seems strange to claim that autonomy is valuable, but that there is no value in actually having one’s autonomous decisions regarding important things in life respected. If exercise of autonomy is also valuable, paternalism for the sake of autonomy is less easily justified, since any infringement of a person’s exercise of her autonomy would be of direct negative value. (2013, 719–20) Pragmatism, on the other hand, Pamental argues, embraces the view that the role of philosophy is to change the world. Pragmatism is a form of what he terms “radical empiricism”: “At its heart, radical empiricism presupposes two things: first, that experience is more than simply phenomenological . . . [and second] experience can provide us with both the tools for making things better and the criteria for evaluating what better means” (2013, 728). Moreover, pragmatism is a form of moral contextualism: “. . . any feature of a situation is potentially morally significant, but that even generally accepted moral features are not always so” (2013, 737). As a result, moral principles are not absolutes; they are contingent and relative to the subjective interests of particular individuals, who themselves are situated within particular cultural and social backgrounds. It is this practical starting point, he argues, that both sets the moral context and directs moral inquiry in the clinical setting. What are our moral duties? In terms of which ranking of cardinal human goods and right-making conditions ought we to evaluate the moral significance of medical research on human subjects, reproductive liberty and abortion, organ transplantation, medical deception and euthanasia? As this issue of The Journal of Medicine and Philosophy makes clear, the field of bioethics faces a plurality of moral rationalities that are grounded in various rankings of cardinal values and right-making conditions, calculations of harms and benefits, claims to virtue or vice, as well as competing understandings of human flourishing. Different rankings and accounts of right-making conditions also presume divergent rules of moral evidence and valid moral inference. All such standards also appear to be deeply embedded within and conditioned by particular cultural and social circumstances (see, e.g., Cherry, 2012; Delkeskamp-Hayes, 2012; Engelhardt, 2012). Insofar, as all we have to work with are our and contingent subjective of itself to be once precisely on is the of all

Fiona A. Miller

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