Plain Language Summaries of Clinical Trial Results: A Preliminary Study to Assess Availability of Easy-to-Understand Summaries and Approaches to Improving Public Engagement.

BACKGROUND: Easy-to-understand, stand-alone factual summaries of clinical trial results have the potential to improve public understanding of and engagement with pharmaceutical research. The European Clinical Trial Regulation (EU) No. 536/2014 is a major regulatory initiative that will result in a large number of such plain language summaries (PLSs) posted in the public domain. Today, however, little is known about the extent to which PLSs are written and are available to the general public. OBJECTIVES: This preliminary study assessed (i) 20 top pharmaceutical companies' positions on improving transparency and commitment to disclosing trial result summaries in an easy-to-understand format and (ii) the availability of such summaries in the public domain and the ease of locating them via general web searches. METHODS: The availability of PLSs in the public domain was estimated based on the number of EudraCT technical result summaries in four disease areas: chronic obstructive pulmonary disease, asthma, meningitis, and influenza. The likelihood of PLSs being easy to find through internet search engine queries by members of the public was assessed using Google. RESULTS: All 20 sponsors had committed to improve clinical trial transparency, 17 committed to sharing PLSs with trial participants, and 14 had at least one PLS available in the public domain. A total of 99 clinical studies in these four disease areas had technical summaries posted on EudraCT between 1 January 2017 and 30 June 2020. Of these 99, 14 studies had PLSs in the public domain. A total of 12 of 14 PLSs were directly captured by search engine. However, the sponsor trial identifier or EudraCT number had to be included in the search term to locate them. Generic search terms resulted in large volumes of non-relevant results. CONCLUSION: Despite the progressive movement towards clinical trial transparency, easily accessible PLSs on clinical trials are currently scarce. The provision of a European mandate and framework for non-technical result summaries by Regulation (EU) 536/2014 will be a major step to bring about positive change.

More patient and public involvement in healthcare research will help to speed the process of making new medicines. This is known by both the regulators and the healthcare industry. The healthcare industry wants to make more information on human research studies available to patients and the public. One way to help achieve this is to write simple summaries of clinical study results. Here, we use the term plain language summary (PLS) to describe them. The PLS allows people to understand human research studies more clearly. A new law will soon make it necessary to write a PLS for every clinical study done in Europe. But, today, is the PLS being used to inform the public about clinical research studies? And what is its potential? We found only  a few researchers have already begun to write PLSs. PLSs on most studies are not available to the public. Even those PLSs on public websites are very hard to find through a Google search. To better understand the potential of PLSs we are doing more research. This research will look at what the public wants to know about these studies and how they will retrieve this information.

Chimpanzees' understanding of social leverage.

Social primates can influence others through the control of resources. For instance, dominant male chimpanzees might allow subordinates access to mate with females in exchange for social support. However, little is known about how chimpanzees strategically use a position of leverage to maximize their own benefits. We address this question by presenting dyads of captive chimpanzee (N = 6) with a task resulting in an unequal reward distribution. To gain the higher reward each individual should wait for their partner to act. In addition, one participant had leverage: access to an alternative secure reward. By varying the presence and value of the leverage we tested whether individuals used it strategically (e.g. by waiting longer for partners to act when they had leverage in the form of alternatives). Additionally, non-social controls served to show if chimpanzees understood the social dilemma. We measured the likelihood to choose the leverage and their latencies to act. The final decision made by the chimpanzees did not differ as a function of condition (test versus non-social control) or the value of the leverage, but they did wait longer to act when the leverage was smaller-particularly in test (versus non-social control) trials suggesting that they understood the conflict of interest involved. The chimpanzees thus recognized the existence of social leverage, but did not use it strategically to maximize their rewards.

Capacity for Preferences: Respecting Patients with Compromised Decision-Making.

When a patient lacks decision-making capacity, then according to standard clinical ethics practice in the United States, the health care team should seek guidance from a surrogate decision-maker, either previously selected by the patient or appointed by the courts. If there are no surrogates willing or able to exercise substituted judgment, then the team is to choose interventions that promote a patient's best interests. We argue that, even when there is input from a surrogate, patient preferences should be an additional source of guidance for decisions about patients who lack decision-making capacity. Our proposal builds on other efforts to help patients who lack decision-making capacity provide input into decisions about their care. For example, "supported," "assisted," or "guided" decision-making models reflect a commitment to humanistic patient engagement and create a more supportive process for patients, families, and health care teams. But often, they are supportive processes for guiding a patient toward a decision that the surrogate or team believes to be in the patient's medical best interests. Another approach holds that taking seriously the preferences of such a patient can help surrogates develop a better account of what the patient's treatment choices would have been if the patient had retained decision-making capacity; the surrogate then must try to integrate features of the patient's formerly rational self with the preferences of the patient's currently compromised self. Patients who lack decision-making capacity are well served by these efforts to solicit and use their preferences to promote best interests or to craft would-be autonomous patient images for use by surrogates. However, we go further: the moral reasons for valuing the preferences of patients without decision-making capacity are not reducible to either best-interests or (surrogate) autonomy considerations but can be grounded in the values of liberty and respect for persons. This has important consequences for treatment decisions involving these vulnerable patients.

Informed consent and the readability of the written consent form.

Introduction The aim of this study was to objectively ascertain the level of readability of standardised consent forms for orthopaedic procedures. Methods Standardised consent forms (both in summary and detailed formats) endorsed by the British Orthopaedic Association (BOA) were retrieved from orthoconsent.com and assessed for readability. This involved using an online tool to calculate the validated Flesch reading ease score (FRES). This was compared with the FRES for the National Health Service (NHS) Consent Form 1. Data were analysed and interpreted according to the FRES grading table. Results The FRES for Consent Form 1 was 55.6, relating to the literacy expected of an A level student. The mean FRES for the BOA summary consent forms (n=27) was 63.6 (95% confidence interval [CI]: 61.2-66.0) while for the detailed consent forms (n=32), it was 68.9 (95% CI: 67.7-70.0). All BOA detailed forms scored >60, correlating to the literacy expected of a 13-15-year-old. The detailed forms had a higher FRES than the summary forms (p<0.001). Conclusions This study demonstrates that the BOA endorsed standardised consent forms are much easier to read and understand than the NHS Consent Form 1, with the detailed BOA forms being the easiest to read. Despite this, owing to varying literacy levels, a significant proportion of patients may struggle to give informed consent based on the written information provided to them.

From conflict and misunderstanding to respect.

Sociologists of the 19th and the 20th centuries were tackling the relation between science and religion. A few models of these relations were offered, by which the monopoly over the truth by any one of those is crashed. Therefore, there are a few models but each is with lots of limitations. None is sufficient to explain the relation between the science and religion, but each contributes to certain extent to better understanding of those relations. Almost every one of the interpretations was under the influence of the social (particularly ideological and political) conditions in which they were emerging. One of those could be named as "Riding on an old horse: there is no reconciliation between faith and reason". Is the enlightenment theory the source of a conflict between "faith" and "reason"? What is it that leads to the conflict of the science and religion? From rejection to acceptance - a view on Darwin's theory then and now. do creationist theories lead to exacerbation of relations between the science and religion? Postmodernism on the relation of science and religion. Stand views of religious communities - science and religion are not in conflict. Examples that confirm such opinion. Many priests and Islamic teachers have given their contributions to the development of science (technology, medicine, geography, architecture, urbanism, music etc.). Isn't it that the calendars, past (Egyptian, Chinese, Aztec etc.) and present (Hindu, Jewish, Islamic, Gregorian etc.) have come from the umbrella of religions. Are conflicts between science and religion the matter of the past? Disputes over use of drugs in rituals exist even today. Religion and science are autonomous fields - but where is the border between them? Technology and religions. How religions refer to technology. Examples of applications of technical achievements in religious activities. An ecological theory that is being developed within sociology of religion focuses on the relation of religions and religious communities toward nature. Contemporary dilemmas (ethic discussions within the field of biomedicine - euthanasia, abortion, organ donation, aesthetic surgery etc.).

Pharma Websites and "Professionals-Only" Information: The Implications for Patient Trust and Autonomy.

BACKGROUND: Access to information is critical to a patient's valid exercise of autonomy. One increasingly important source of medical information is the Internet. Individuals often turn to drug company ("pharma") websites to look for drug information. OBJECTIVE: The objective of this study was to determine whether there is information on pharma websites that is embargoed: Is there information that is hidden from the patient unless she attests to being a health care provider? We discuss the implications of our findings for health care ethics. METHODS: We reviewed a convenience sample of 40 pharma websites for "professionals-only" areas and determined whether access to those areas was restricted, requiring attestation that the user is a health care professional in the United States. RESULTS: Of the 40 websites reviewed, 38 had information that was labeled for health care professionals-only. Of these, 24 required the user to certify their status as a health care provider before they were able to access this "hidden" information. CONCLUSIONS: Many pharma websites include information in a "professionals-only" section. Of these, the majority require attestation that the user is a health care professional before they can access the information. This leaves patients with two bad choices: (1) not accessing the information or (2) lying about being a health care professional. Both of these outcomes are unacceptable. In the first instance, the patient's access to information is limited, potentially impairing their health and their ability to make reasonable and well-informed decisions. In the second instance, they may be induced to lie in a medical setting. "Teaching" patients to lie may have adverse consequences for the provider-patient relationship.

An activist's argument that participant values should guide risk-benefit ratio calculations in HIV cure research.

The patient empowerment movement, spurred by AIDS activism in the 1980s, quickly evolved to encompass how study participants are considered and treated in clinical research. Initially, people fearing death of AIDS sought early access to experimental medications that had not undergone rigorous testing in hopes of extending their lives. Thirty years on, scientists are asking a different set of ethical questions about clinical research, this time in the pursuit of either a sterilising cure or long-term remission for HIV. Instead of hastening access to experimental drugs for the sickest, researchers are now testing interventions for eradicating or controlling the virus in typically very healthy HIV-positive individuals who have the most to lose from such interventions if something goes wrong. While clinical researchers and ethicists debate the merits and limits of this type of research they should avoid discounting altruistic motivations as a powerful factor in a prospective study participant's decisions to assume risks. My conversations with four men who participated in HIV cure studies confirmed the capacity of these people to make carefully considered decisions about risks and the sometimes substantial influence/sway of non-clinical benefits that may come from participation in cure-oriented research. Studies must undergo ethical and clinical review before proceeding, and not all participants of such studies will be able to weigh or understand risks and benefits as those profiled here. But respecting the self-agency of people living with HIV should be a goal in the design and conduct of cure research.

Informed consent to HIV cure research.

Trials with highly unfavourable risk-benefit ratios for participants, like HIV cure trials, raise questions about the quality of the consent of research participants. Why, it may be asked, would a person with HIV who is doing well on antiretroviral therapy be willing to jeopardise his health by enrolling in such a trial? We distinguish three concerns: first, how information is communicated to potential participants; second, participants' motivations for enrolling in potentially high risk research with no prospect of direct benefit; and third, participants' understanding of the details of the trials in which they enrol. We argue that the communication concern is relevant to the validity of informed consent and the quality of decision making, that the motivation concern does not identify a genuine problem with either the validity of consent or the quality of decision making and that the understanding concern may not be relevant to the validity of consent but is relevant to the quality of decision making. In doing so, we derive guidance points for researchers recruiting and enrolling participants into their HIV cure trials, as well as the research ethics committees reviewing proposed studies.

How to keep high-risk studies ethical: classifying candidate solutions.

This article lays out a wide spectrum of candidate ethical solutions for the challenge on which this JME symposium focuses: the benefit:risk ratio challenge to some early-phase HIV cure and remission studies. These candidate solutions fall into four categories: ones that seek to reduce risks in early-phase HIV cure and remission studies, ones that enhance the benefits for these studies' participants (or show that those were adequate in the first place), ones that focus on participants' free and informed consent to participate and ones according to whom the large benefits to non-participants can defeat considerations about individual participant net risks. In so doing, this article also structures the rest of the symposium.

For love and money: the need to rethink benefits in HIV cure studies.

HIV cure research holds great potential to eradicate HIV, but the benefit to early trial participants is likely to be small. Moreover, participation carries unknown and possibly significant risks to research participants. This is the risk:benefit ratio challenge of HIV cure research. Although it may be consensual and rational for individuals to participate in HIV cure research that requires a degree of self-sacrifice, I argue that altruistic research participants can be exploited when the benefits to them are unfair. Transactions of this kind should not be prohibited, as that would be unacceptably paternalistic and thwart socially valuable research. Nevertheless, we should not simply accept these transactions but must work to reduce or eliminate exploitation by enhancing the benefits so that research participants are better off by their own lights. Offering payment in HIV cure research is the optimal way to enhance benefits to research participants and to make the risk:benefit ratio more favourable. I argue for a payment-as-benefit model against the standard view, assumed in ethics and policy, that offers of payment are not legitimate benefits.

First-in-human HIV-remission studies: reducing and justifying risk.

Interest and excitement surround the possibility of developing measures that produce sustained or permanent HIV remission in infected individuals. First-in-human (FIH) trials are one step in exploring this possibility. Initial human trials raise the usual ethical issues associated with human research, and a set of distinct issues. Because the potential direct benefits to FIH trial volunteers will be either small or non-existent, trial risks must be justified by the social value of the information the trials are expected to produce. To minimise and justify risks, researchers must have solid preclinical evidence that FIH trials will be safe and produce information relevant to human health improvements. Researchers must also adopt adequate study safeguards to protect FIH subjects. An ethically defensible study population must be selected as well.

The benefit/risk ratio challenge in clinical research, and the case of HIV cure: an introduction.

This piece introduces the JME symposium 'The benefit/risk ratio challenge in clinical research, and the case of HIV cure.'

Cure research and consent: the Mississippi Baby, Barney Clark, Baby Fae and Martin Delaney.

Trials using children as subjects are much more problematic from an informed consent perspective than trials on competent adults, although the 'therapeutic misconception' is a central concern in both. The role of famous experiments and the use of one individual's experience to designate and justify a whole category of research have always threatened to undermine the validity of informed consent to research by making it seem to be a validated therapy. In research, the unintended consequence of 'naming' based on goals ('cure') or specific individuals (like the Mississippi Baby) tends to subvert informed consent when the famous case is a 'success', and to prematurely end a line of research if the named subject dies. Names, including the Mississippi Baby, Barney Clark, Baby Fae and even Martin Delaney, are more suggestive of fantasy than science. The word 'cure' should not be used in obtaining consent for HIV 'cure trials', and names of people involved in past experiments should be avoided in the informed consent process. These two modest proposals should reduce the risks of the therapeutic misconception in 'cure research'.

Preschoolers' understanding of merit in two Asian societies.

Recent research in moral psychology have suggested that children make judgments about distributive justice early on in development, and in particular they appear to be able to use merit when distributing the benefits of a collective action. This prediction has recently been validated in various western cultures but it is unknown whether it also applies to more collectivistic cultures, in which the group might be favoured over the individual, and need over merit. Here, we investigate merit-based distributions among 81 children belonging to two Asian societies, China and Japan (mean age = 5.0 years). In line with the idea that children's moral psychology develops early, we found that Chinese and Japanese children are able to use merit to distribute the benefits of a collective action.

Hot baths and cold minds: neuroscience, mind reading, and mind misreading.

The idea-the possibility-of reading the mind, from the outside or indeed even from the inside, has exercised humanity from the earliest times. If we could read other minds both prospectively, to discern intentions and plans, and retrospectively, to discover what had been "on" those minds when various events had occurred, the implications for morality and for law and social policy would be immense. Recent advances in neuroscience have offered some, probably remote, prospects of improved access to the mind, but a different branch of technology seems to offer the most promising and the most daunting prospect for both mind reading and mind misreading. You can't have the possibility of the one without the possibility of the other. This article tells some of this story.

Intervención en cuidadores informales de pacientes con demencia en Colombia: una revisión / Intervention in informal caregivers of Patients with dementia in Colombia: a review

El incremento de la población adulta mayor, eleva de forma proporcional las enfermedades crónicas que esta puede padecer. Esta situación genera una condición de dependencia y vulnerabilidad por lo que uno de los integrantes de la familia debe asumir el rol de cuidador informal. Desempañar este rol implica experimentar sentimientos de culpa, sentimientos de impotencia y resignación, alteraciones del sueño, entre otros. Ante estos hallazgos se han diseñado intervenciones para los cuidadores informales desde finales de los años 70 hasta la actualidad, tendientes a disminuir el malestar que el cuidado conlleva, donde se destacan la efectividad de las intervenciones psicoeducativas y psicológicas, así mismo, las intervenciones que utilizan el modelo cognitivo-conductual por los efectos en el cambio de percepción de la autoeficacia y la modificación de los pensamientos disfuncionales que mantiene el cuidador en el desempeño de su rol. Sin embargo, los estudios realizados hasta el momento, se han dirigido más hacia el conocimiento de la enfermedad y su cuidado. Existen estudios en relación al estrés adaptado al cuidado considerando factores internos, externos y contextuales para entender el malestar que representa el cuidado, sin embargo, son pocos, considerando el incremento de esta problemática.

The increase in the older population, increases proportionally chronic diseases they can suffer. This creates a condition of dependency and vulnerability as one of the family members must assume the role of informal caregiver. Defog this role involves experiencing guilt, feelings of helplessness and resignation, sleep disturbances among others. Given this finding, Have been designed interventions for informal caregivers from the late 70s to the present, aimed at reducing the discomfort associated care, highlighting the effectiveness of psycho-educational and psychological interventions Likewise, interventions that use cognitive-behavioral model for the effects on the change in perception of selfefficacy and changing the disfunctional thoughts that keeps the caregiver in the performance of their role. However, studies so far have been directed towards the understanding of the disease and its care. there are studies in relation to stress considering carefully adapted to internal, external and contextual understanding discomfort of caring factors, however, are few considering the increase of this problem.

Neuroethics in a "psy" world. The case of Argentina.

Given the cultural psychoanalytic tradition that shapes the thought of Argentineans and their current skepticism with regard to neurosciences when it comes to understanding human behavior, this article addresses the question of how a healthy neuroethics can develop in the country.

Doing what might be "wrong": understanding internists' responses to professional challenges.

PURPOSE: To develop a deeper understanding of the complexity of physicians' decision making when faced with professional challenges. METHOD: Using constructivist grounded theory, the authors conducted a secondary analysis of transcripts from focus groups with 40 internists in 2011. Participants responded to scripted professional challenge scenarios. The authors analyzed the transcripts for instances in which participants discussed "doing what might be wrong" (i.e., something that goes against their values or others' expectations). They used the theory of planned behavior (TPB), which posits that intention to act is predicted by attitudes, subjective norms, and perceived behavioral control, to understand the findings in a broader context. RESULTS: The theme of "doing what might be wrong" was pervasive, particularly in response to scenarios involving stewardship, nonpatients' requests for advice or care, or requests for e-mail access. Participants' rationales for suggested behaviors included a desire to keep patients happy and be (or appear) helpful. Modifiers of those responses included type of patient, physician's relationship with the patient, and comfort level with the request. Consistent with the TPB, attitudes or beliefs about the intended behavior, subjective norms, and perceived behavioral control influenced decision making. CONCLUSIONS: Physicians often do what might be wrong when they are asked to do something that goes against their values and beliefs, by patients, others, or as perceived by their organizations. Actions are often rationalized as being done for the right reasons. These findings should inform the development of educational initiatives to support physicians in acting in accordance with their ideals.

Informed consent as an ethical requirement in clinical trials: an old, but still unresolved issue. An observational study to evaluate patient's informed consent comprehension.

We explored the comprehension of the informed consent in 77 cancer patients previously enrolled in randomised phase II or phase III clinical trials, between March and July 2011, at the San Raffaele Scientific Institute in Milano. We asked participants to complete an ad hoc questionnaire and analysed their answers. Sixty-two per cent of the patients understood the purpose and nature of the trial they were participating in; 44% understood the study procedures and 40% correctly listed at least one of the major risks or complications related to their participation in the trial. We identified three factors associated with comprehension of the informed consent: age, education and type of tumour/investigator team. We suggest several possible improvements of how to obtain informed consent that will increase patient awareness, as well as the validity and effectiveness of the clinical trials.