Several high-profile episodes have recently thrust drug safety and the pharmaceutical industry's practices into the spotlight. Merck's recall of the drug Vioxx, for instance, was a major news event. GlaxoSmithKline's suppression of data linking suicidal behavior among children to Paxil also galvanized tremendous public attention. What differentiates these events from the usual evolving process of scientific knowledge, and marks them with an aura of “scandal,” are questions about the propriety of corporate behavior. Who knew what, and when did they (...) know it? Concerns are growing about the potential for industry sponsors to suppress negative results from clinical trials research. Scientists, medical journal editors, legislators, and the public have called for greater transparency in the conduct of clinical trials and the drug approval process. (shrink)

Several high-profile episodes have recently thrust drug safety and the pharmaceutical industry's practices into the spotlight. Merck's recall of the drug Vioxx, for instance, was a major news event. GlaxoSmithKline's suppression of data linking suicidal behavior among children to Paxil also galvanized tremendous public attention. What differentiates these events from the usual evolving process of scientific knowledge, and marks them with an aura of “scandal,” are questions about the propriety of corporate behavior. Who knew what, and when did they (...) know it? Concerns are growing about the potential for industry sponsors to suppress negative results from clinical trials research. Scientists, medical journal editors, legislators, and the public have called for greater transparency in the conduct of clinical trials and the drug approval process. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:A Trial of PatienceChristopher LewisIt seemed like after two weeks, my “flu” symptoms should have resolved. I was not eating, could not hold anything down, and had no energy. It was easy enough for my pediatrician at the time to attribute this to a common virus. This was not sitting well with my parents, however. My mother decided to take me to the emergency room and get me evaluated (...) there. The doctors there assessed me and sent me back home with a medication to help with the nausea. Later that evening, my mom gave me that medication, and it caused a seizure. She called 911, and I was brought by ambulance to the hospital. After an extensive workup, it was determined I was in liver failure related to an aneurysm in my hepatic artery. I was going to require a liver transplant if I were to live. I had to be transferred to another hospital in New York from the hospital near our home in Connecticut. I do not remember any of the details leading up to this after the seizure. I do not remember being told I needed a liver transplant and I do not remember going into surgery.My memories of these events start after the surgery. What I remember is being in the pediatric ICU and being told my mother was able to donate part of her liver to me. I had quite a lengthy recovery after this point. I spent about two months in the hospital and then went to a rehab facility where I would have to learn how to walk again and regain my strength.By the time I was discharged from the rehab facility, I had missed the last half of my 5th-grade year. By the time I was able to return to school, it was already several months into 6th grade. Slowly but surely, life was returning to normal. I was able to get back to doing the things an eleven-year-old should be doing. For twelve years after this initial transplant, I was in great health, my transplant team was happy with how I was doing, and I just required annual checkups after a while. Unfortunately, I saw as a child how fast things can change. This was once again the case. [End Page 126]I was in my last week of college classes, just about to finish my Bachelor’s degree in nursing and looking forward to starting my career as a nurse in the neuro ICU. However, I once again became acutely ill with seemingly flu-like symptoms. After a few days of dealing with these symptoms, my mother brought me to the emergency room. When we got to the emergency room, they did some initial testing and told me I would need to be admitted for antibiotic therapy. The first thought that came to my mind was, “Would I be able to be discharged in time to take my final exams next week?”Once I arrived in my hospital room, I met with my transplant team. They delivered the grave news. The imaging they had done showed that the graft artery from my original liver transplant as a child had failed. The graft had thrombosed and I had infected bilomas in my liver. Now, twelve years later, I would need to be re-listed for another transplant. I was devastated and in disbelief. I recall telling my mother, who was with me at the time, that we should hold off on telling my dad, thinking this could not be possible, and we shouldn’t worry him over something that was not necessarily true. Unfortunately, however, this was my reality. I would go on to wait a little over two years for the perfect liver from a deceased donor.The road to being listed and ultimately having a repeat transplant was not without its challenges and bumps in the road. About three months into my two-year wait for a liver transplant, I received my first offer for a liver. I went through all of the pre-op preparation and the next morning went into the OR and underwent anesthesia. However, I... (shrink)

Background. Informed consent (IC) is not only a regulatory but also an ethical requirement to participate in any clinical trial. It is essential to determine that research participants understand what they consent to. Studies that evaluate participants’ understanding of IC conclude that recall and understanding of IC is often low, and researchers recommend that interactive multimedia interventions should be implemented to optimise understanding. Objectives. To assess participants’ understanding of IC of the research trial that they agreed to participate in.Methods. (...) A descriptive survey design, within a quantitative research approach, was used to conduct the study at two government hospitals in the Eastern Cape Province. A semi-structured, self-administered questionnaire was used to collect information from 170 participants in research studies. Descriptive statistics were used to analyse the results.Results. Participants were recruited from among women who enrolled in any of the three studies that were ongoing at the two sites during the recruitment period. The study participants had a mean age of 25.9 years. Nearly one-third (30%) could not recall the purpose of the original trial that they consented to. The concept of randomisation was not understood by any of the participants.Conclusion. Regardless of extensive efforts to ensure that participants understood their participation, this study unveiled poor recall of essential information on IC. It is proposed that IC should be short and only address essential components such as purpose, procedure, possible risks or benefits, alternative options if not participating and explaining the concept of voluntary participation. (shrink)

BackgroundInformed consent is an ethical and legal requirement for research involving human participants. However, few studies have evaluated the process, particularly in Africa.Participants in a case control study designed to identify correlates of immune protection against tuberculosis (TB) in South Africa. This study was in turn nested in a large TB vaccine efficacy trial.The aim of the study was to evaluate the quality of consent in the case control study, and to identify factors that may influence the quality of consent.Cross-sectional (...) study conducted over a 4 month period.MethodsConsent was obtained from parents of trial participants. These parents were asked to complete a questionnaire that contained questions about the key elements of informed consent (voluntary participation, confidentiality, the main risks and benefits, etc.). The recall (success in selecting the correct answers) and understanding (correctness of interpretation of statements presented) were measured.ResultsThe majority of the 192 subjects interviewed obtained scores greater than 75% for both the recall and understanding sections. The median score for recall was 66%; interquartile range (IQR) = 55%–77% and for understanding 75% (IQR = 50%–87%). Most (79%) were aware of the risks and 64% knew that they participated voluntarily. Participants who had completed Grade 7 at school and higher were more likely (OR = 4.94; 95% CI = 1.57 – 15.55) to obtain scores greater than 75% for recall than those who did not. Participants who were consented by professional nurses who had worked for more than two years in research were also more likely (OR = 2.62; 95% CI = 1.35–5.07) to obtain such scores for recall than those who were not.ConclusionNotwithstanding the constraints in a developing country, in a population with low levels of literacy and education, the quality of informed consent found in this study could be considered as building blocks for establishing acceptable standards for public health research. Education level of respondents and experience of research staff taking the consent were associated with good quality informed consent. (shrink)

Background and objectives: There are few insights from sub-Saharan Africa on research participants’ experiences of the informed consent process, particularly in the context of randomised controlled trials, where issues of randomisation and the use of placebos may be confusing concepts for participants. This study investigated the knowledge and perceptions of the informed consent process among individuals participating in influenza vaccine trials in two disadvantaged communities in South Africa.Method: Four to 12 months after completion of the trials, participants (...) were contacted to return to participate in the informed consent study. The semistructured questionnaire administered to assess recall of trial procedures and the informed consent process covered key issues including: purpose of the study; awareness that the study was not part of routine treatment; voluntary nature of participation and freedom to withdraw; randomisation; placebos; and remuneration.Results: A total of 334 participants completed the questionnaire. Only 21% were able to recall that they were allocated randomly to the different treatment arms. Only 19% of those involved in the placebo controlled study had interpreted the concept of placebo as an inactive medication.Conclusion: Although a good general recall of trial concepts was demonstrated, only a small proportion of the participants correctly interpreted and recalled the concepts of randomisation and placebos. Informed consent in this and similarly disadvantaged communities may often be inadequate and new ways to improve understanding of the research process should be explored. (shrink)

ObjectiveThis study aimed to describe how parents and physicians experienced the informed consent interview and to investigate the aspects of the relationship that influenced parents’ decision during the consent process for a randomised clinical trial in a tertiary neonatal intensive care unit. The secondary objective was to describe the perspectives of parents and physicians in the specific situation of prenatal informed consent.SettingSingle centre study in NICU of the Centre Hospitalier Intercommunal de Créteil, France, using a convenience period from February to (...) May 2016.DesignAncillary study to a randomised clinical trial: Prettineo. Records of interviews for consent. Population: parents and physicians. Mixed study including qualitative and quantitative interview data about participants’ recall and feelings about the consent process. Interviews were reviewed using thematic discourse analysis.ResultsParents’ recall and understanding of the study’s main goal and design was good. Parents and physicians had a positive experience, and trust was one of the main reasons for parents to consent. Misunderstanding was the main reason for refusal.Before birth, three situations can compromise parents’ consent: the mother already consented to participate in other studies, the absence of the father during the interview and the feeling that the baby’s birth is not an imminent possibility.ConclusionsConfronting parents and physicians’ perspectives in research can help us reach answers to sensitive issues such as content and timing of information. Each different types of study raises different ethical dilemmas for consent that might be discussed in a more individual way. (shrink)

Objective: To pilot informed consent materials developed for Aboriginal parents in a vaccine trial, and evaluate their design and the informed consent process.Methods: Cross sectional quantitative and qualitative survey of 20 Aboriginal and 20 non-Aboriginal women in Alice Springs. Information about the proposed research was presented to Aboriginal participants by an Aboriginal researcher, using purpose designed verbal, visual, and written materials. Non-Aboriginal participants received standard materials developed by the sponsor. Questionnaires were used to evaluate recall and understanding immediately and (...) five days later. Qualitative analysis of Aboriginal participants’ interviews was performed.Results: There were no differences between the groups in understanding of diseases prevented by the vaccine, the potential risks of participating, or the voluntary nature of participation. Most Aboriginal participants had difficulty with the concept of a “licensed” versus “unlicensed” vaccine. The non-Aboriginal group had a good understanding of this. Aboriginal participants identified the use of the flipchart, along with a presentation by a doctor and Aboriginal health worker, as preferred delivery modes. Group presentations were preferred rather than one-on-one discussions. The use of the questionnaire posed considerable methodological difficulties.Conclusions: A one-off oral presentation to Aboriginal participants is unlikely to produce “informed consent”. Key but unfamiliar concepts require identification and particularly considered presentation. (shrink)

ObjectivesThe present study explores the effect of visual art training on people with dementia, utilizing a randomized control trial design, in order to investigate the effects of an 8-week visual art training program on cognition. In particular, the study examines overall cognition, delayed recall, and working memory, which show deficits in people with dementia.MethodFifty-three individuals with dementia were randomly assigned into either an art training or usual-activity waitlist control group. Overall cognition and delayed recall were assessed with the (...) Montreal Cognitive Assessment, and working memory was assessed with the Backward Digit Span task.ResultsThere were no group differences in overall cognition, or working memory, while a difference in delayed recall was undetermined, based on post-test—pre-test difference scores. Groups were comparable at baseline on all measures.ConclusionThe measures of cognition, delayed recall, and working memory used in this study were not affected by an 8-week visual art training program.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT03175822. (shrink)

In this proof-of-concept study, we assessed the potential for immersive virtual reality to measure transfer following strategic memory training, and whether efficacy and transfer are increased when training is complemented by practice in an immersive virtual environment. Forty older adults with subjective memory complaints were trained with the method of loci. They were randomized to either a condition where they practiced the strategy in VR or a control condition where they were familiarized with VR using a non-memory task. Training efficacy (...) was measured with word recall, and transfer of the training benefit was measured with a recall task completed in two VR tasks as well as a self-report memory questionnaire. Testing was administered before, midway, and after training. Participants improved their scores on word recall. Regarding transfer measures, participants improved their performance in the two VR recall tasks but not on the self-report memory questionnaire. No significant group effect was observed. Improvement was found when comparing PRE to POST 3 with no further improvement at POST 6. Thus, strategic memory training improved the memory of seniors with memory complaints on word recall and a transfer task relying on a VR scenario that resembles real-life. However, no evidence supporting an increase in transfer effects was found when enriching training with VR memory exercises. (shrink)

Children traditionally learn to read Chinese characters by rote, and thus stretching children’s memory span could possibly improve their reading in Chinese. Nevertheless, 85% of Chinese characters are semantic-phonetic compounds that contain probabilistic information about meaning and pronunciation. Hence, enhancing children’s metalinguistic skills might also facilitate reading in Chinese. In the present study we tested whether training children’s metalinguistic skills or training their working-memory capacity in eight weeks would produce reading gains, and whether these gains would be similar in Chinese (...) and English. We recruited 35 second graders in Hong Kong and randomly assigned them to a metalinguistic training group (N = 13), a working-memory training group (10), or a waitlist control group (12). In the metalinguistic training, children were taught to analyze novel Chinese characters into phonetic and semantic radicals and novel English words into onsets and rimes. In the working-memory training, children were trained to recall increasingly long strings of Cantonese or English syllables in correct or reverse order. All children were tested on phonological skills, verbal working memory, and word reading fluency in Chinese and in English before and after training. Analyses of the pre- and post-test data revealed that only the metalinguistic training group, but not the other two groups, showed significant improvement on phonological skills in Chinese and English. Working-memory span in Chinese and English increased from the pre- to post-test in the working-memory training group relative to other two groups. Despite these domain-specific training effects, the two training groups improved similarly in word reading fluency in Chinese and English compared to the control group. Our findings suggest that increased metalinguistic skills and a larger working-memory span appear equally beneficial to reading fluency, and that these effects are similar in Chinese and English. (shrink)

Research ethics committees (RECs) evaluate whether the risk-benefit ratio of a study is acceptable. Decentralized clinical trials (DCTs) are a novel approach for conducting clinical trials that potentially bring important benefits for research, including several collateral benefits. The position of collateral benefits in risk-benefit assessments is currently unclear. DCTs raise therefore questions about how these benefits should be assessed. This paper aims to reconsider the different types of research benefits, and their position in risk-benefit assessments. We first propose (...) a categorization of research benefits, based on the types of benefits that can be distinguished from the literature and ethical guidelines. Secondly, we will reconsider the position of collateral benefits. We argue that these benefits are not fundamentally different from other benefits of research and can therefore be included in risk-benefit assessments of DCTs. (shrink)

Feelings of knowing (FoK) are introspective self-report ratings of the felt likelihood that one will be able to recognize a currently unrecallable memory target. Previous studies have shown that FoKs are influenced by retrieved fragment knowledge related to the target, which is compatible with the accessibility hypothesis that FoK is partly based on currently activated partial knowledge about the memory target. However, previous results have been inconsistent as to whether or not FoKs are influenced by the accuracy of such information. (...) In our study (N = 26), we used a recall-judge-recognize procedure where stimuli were general knowledge questions. The measure of partial knowledge was wider than those applied previously, and FoK was measured before rather than after partial knowledge. The accuracy of reported partial knowledge was positively related to subsequent recognition accuracy, and FoK only predicted recognition on trials where there was correct partial knowledge. Importantly, FoK was positively related to the amount of correct partial knowledge, but did not show a similar incremental relation with incorrect knowledge. (shrink)

Altered attachment characteristics may disturb the HPA and can even cause changes in the hippocampus. However, it is unknown if that will influence spatial navigation performance, learning and recalling. In this study we pretend to verify if there are differences in spatial navigation learning and was associated with attachment style dimensions of anxiety and close-depend. Sixty-five female participants were recruited and were evaluated using the Adult Attachment Scale-R and tested on a virtual maze navigation task (VMT) at one moment (exploratory (...) trial + 3 trials) and 24h later (3 trials). There was a significant Moment x Trial x Close-Depend interaction for the outcome time, F (2, 126) = 3.807, p = 0.025, with post-hoc analysis indicating that the High Close-Depend group displayed significant improvements between Trial 1 and Trial 3 in the post-test assessment. Conversely, the Low Close-Depend group displayed significant improvements between Trial 1and Trial 3 but on the pre-test assessment. Furthermore, the Low Close-Depend group presented significant better performance in pre-test Trial 3 in comparison to the High Close-Depend group. Thereby, it seems that low comfort with proximity and trust in others is associated with reduced spatial navigation recall, although spatial learning performance was actually superior in these participants. It is possible that reduced exposure to social interaction and meaning relationship may be reduced in the Low Close-Depend group, leading to modifications in hippocampal function and, ultimately, reduced spatial recall. Conversely, participants with high comfort with proximity and trust in others may not display typical spatial learning in the proposed task as they are more willing to freely explore the presented environment. (shrink)

The aim of our study was to test the effectiveness of the “three good things for others” intervention. We used the randomized controlled trial method, with four measurements (pretest, posttest, follow-up after 2 weeks, follow-up after 4 weeks) and with random assignment of participants to experimental and placebo control groups. We investigated the effects of the intervention on prosocial behavior, and in addition on positive and negative affect, and positive orientation (a general tendency to approach reality in a positive way). (...) The results showed an increase in positive affect and a decrease in negative affect in the experimental group a day after the intervention. These effects, however, did not endure over the next 2 or 4 weeks. We also observed a statistically significant increase in prosocial behavior in the placebo control group, in which participants were engaged in a task of recalling childhood memories. The results are discussed and recommendations for future studies are proposed. (shrink)