scholarly journals Unethical informed consent caused by overlooking poorly measured nocebo effects

2020 ◽  
pp. medethics-2019-105903
Author(s):  
Jeremy Howick
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Informed Consent ◽  
Natural History ◽  
Adverse Events ◽  
Placebo Effect ◽  
Nocebo Effect ◽  
Control Groups ◽  
Nocebo Effects ◽  
Negative Outcome

Unlike its friendly cousin the placebo effect, the nocebo effect (the effect of expecting a negative outcome) has been almost ignored. Epistemic and ethical confusions related to its existence have gone all but unnoticed. Contrary to what is often asserted, adverse events following from taking placebo interventions are not necessarily nocebo effects; they could have arisen due to natural history. Meanwhile, ethical informed consent (in clinical trials and clinical practice) has centred almost exclusively on the need to inform patients about intervention risks with patients to preserve their autonomy. Researchers have failed to consider the harm caused by the way in which the information is conveyed. In this paper, I argue that the magnitude of nocebo effects must be measured using control groups consisting of untreated patients. And, because the nocebo effect can produce harm, the principle of non-maleficence must be taken into account alongside autonomy when obtaining (ethical) informed consent and communicating intervention risks with patients.

scholarly journals Placebo and nocebo effects in the neurological practice

2015 ◽  
Vol 73 (1) ◽  
pp. 58-63 ◽  
Author(s):  
Caroline Bittar ◽  
Osvaldo J.M. Nascimento
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Gold Standard ◽  
Neurological Diseases ◽  
Nocebo Effect ◽  
Double Blind ◽  
Positive Effects ◽  
Specific Effects ◽  
Randomized Clinical Study ◽  
Nocebo Effects

Knowledge of placebo and nocebo effects is essential to identify their influence on the results in clinical practice and clinical trials, and thereby properly interpret their results. It is known that the gold standard of clinical trials research is the double-blind, placebo-controlled, randomized clinical study. The objective of this review is to distinguish specific from non-specific effects, so that the presence of positive effects in the group that received placebo (placebo effect) and the presence of adverse effects in the group receiving placebo (nocebo effect) lead to confounding in interpreting the results. Placebo and nocebo effects have been considered in neurological diseases such as depression, pain, headache, multiple sclerosis, epilepsy. As placebo and nocebo effects are also present in clinical practice, the purpose of this review is to draw attention to their influence on neurological practice, calling attention to the development of measures that can minimize them.

scholarly journals Development, piloting, and evaluation of an evidence-based informed consent form for total knee arthroplasty (EvAb-Pilot): a protocol for a mixed methods study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Alina Weise ◽  
Julia Lühnen ◽  
Stefanie Bühn ◽  
Felicia Steffen ◽  
Sandro Zacher ◽  
...  
Keyword(s):  
Total Knee Arthroplasty ◽  
Informed Consent ◽  
Adverse Events ◽  
Knee Arthroplasty ◽  
Evidence Based ◽  
Nocebo Effect ◽  
Legal Requirements ◽  
Consent Forms ◽  
Link Type ◽  
Total Knee

Abstract Background Practitioners frequently use informed consent forms to support the physician-patient communication and the informed consent process. Informed consent for surgery often focuses on risk centered information due to high liability risks for treatment errors. This may affect patients’ anxiety of adverse events and the nocebo effect. This study focuses on the optimization of pre-surgical information on risks and complications, and at the same time reconciles these information with legal requirements. Methods The development, piloting, and evaluation of evidence-based informed consent forms for total knee arthroplasty (TKA) and related anesthesia procedures will follow the UK MRC Framework for developing and evaluating complex interventions. Conducting different sub-studies, we will (I) qualitatively explore the information acquisition and decision-making processes, (II) develop and pilot test evidence-based informed consent forms on the example of TKA and related anesthesia procedures, (III) conduct a monocentric interrupted time series (ITS) pilot study to evaluate the effects of evidence-based informed consent forms in comparison with standard consent forms, and (IV) perform a process evaluation to identify barriers and facilitators to the implementation of the intervention and to analyze mechanisms of impact. Discussion The evidence-based and understandable presentation of risks in informed consent forms aims at avoiding distorted risk depiction and strengthening the patients’ competencies to correctly assess the risks of undergoing surgery. This might reduce negative expectations and anxiety of adverse events, which in turn might reduce the nocebo effect. At the same time, the practitioners’ acceptance of evidence-based informed consent forms meeting legal requirements could be increased. Trial registration ClinicalTrials.gov, NCT04669483. Registered 15 December 2020. German Clinical Trials Registry, DRKS00022571. Registered 15 December 2020

scholarly journals Placebo and nocebo effects in youth: subjective thermal discomfort can be modulated by a conditioning paradigm utilizing mental states of low and high self-efficacy

2021 ◽  
pp. 204946372110200
Author(s):  
Ella Weik ◽  
Regula Neuenschwander ◽  
Karin Jensen ◽  
Tim F Oberlander ◽  
Christine Tipper
Keyword(s):  
Placebo Effect ◽  
Self Efficacy ◽  
Group Analysis ◽  
Structured Interview ◽  
Thermal Stimulus ◽  
Nocebo Effect ◽  
Conditioning Paradigm ◽  
Significant Difference ◽  
Nocebo Effects ◽  
Subjective Discomfort

Introduction: Conditioning is a key mechanism of placebo and nocebo effects in adults, but little is known about these effects in youth. This study investigated whether personalized verbal cues evoking a sense of high or low self-efficacy can induce conditioned placebo and nocebo effects on subjective discomfort of noxious heat in youth. Methods: In a structured interview, 26 adolescents (13–18 years) described personal situations in which they experienced a sense of high, low or neutral self-efficacy. Participants were then asked to recall these memories during a conditioning paradigm, in which a high thermal stimulus applied to the forearm was repeatedly paired with a low self-efficacy cue and a low thermal stimulus with a high self-efficacy cue. In a testing phase, high, low and neutral self-efficacy cues were paired with the same moderate temperature. We hypothesized that conditioned high and low self-efficacy cues would induce conditioned placebo and nocebo responses to moderate temperatures. Results: Moderate temperatures were rated as more uncomfortable when paired with the conditioned low compared with the neutral self-efficacy cue (nocebo effect). While in the whole-group analysis, there was no significant difference between ratings of moderate thermal stimuli paired with high compared with neutral self-efficacy cues (placebo effect), a sub-group of participants with a greater range of emotional valence between high and neutral self-efficacy cues revealed a significant placebo effect. The strength of the nocebo effect was associated with higher anxiety and lower hope. Conclusion: Conditioned associations using internal self-efficacy states can change subjective discomfort of thermal sensations.

scholarly journals How I manage ibrutinib intolerance and complications in patients with chronic lymphocytic leukemia

Blood ◽  
2019 ◽  
Vol 133 (12) ◽  
pp. 1298-1307 ◽  
Author(s):  
Deborah M. Stephens ◽  
John C. Byrd
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Chronic Lymphocytic Leukemia ◽  
Adverse Events ◽  
Real World ◽  
Lymphocytic Leukemia ◽  
Targeted Therapeutics ◽  
Therapeutic Approaches ◽  
Therapeutic Alternatives

Abstract Chronic lymphocytic leukemia (CLL) therapy has changed dramatically with the introduction of several targeted therapeutics. Ibrutinib was the first approved for use in 2014 and now is used for initial and salvage therapy of CLL patients. With its widespread use in clinical practice, ibrutinib’s common and uncommon adverse events reported less frequently in earlier clinical trials have been experienced more frequently in real-world practice. In particular, atrial fibrillation, bleeding, infections, and arthralgias have been reported. The management of ibrutinib’s adverse events often cannot be generalized but must be individualized to the patient and their long-term risk of additional complications. When ibrutinib was initially developed, there were limited therapeutic alternatives for CLL, which often resulted in treating through the adverse events. At the present time, there are several effective alternative agents available, so transition to an alternative CLL directed therapy may be considered. Given the continued expansion of ibrutinib across many therapeutic areas, investigation of the pathogenesis of adverse events with this agent and also clinical trials examining therapeutic approaches for complications arising during therapy are needed. Herein, we provide strategies we use in real-world CLL clinical practice to address common adverse events associated with ibrutinib.

The FDA's Proposal for Public Disclosure of Adverse Events in Gene Therapy Trials

2000 ◽  
Vol 19 (2) ◽  
pp. 261-268
Author(s):  
Deborah R. Barnbaum
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Informed Consent ◽  
Adverse Events ◽  
Drug Administration ◽  
Food And Drug Administration ◽  
Public Disclosure

In January 2001, the Food and Drug Administration (FDA) proposed annual public disclosure of adverse events during gene therapy and xenotransplantation trials. The proposed policy raises the following questions: (1) Is the reformed policy in accord with the FDA's long-standing informed consent policies? (2) Why pair gene therapy trials and xenotransplantation trials in the revised guidelines? (3) Why single out these trials for public disclosure of adverse events? Each question is examined, and three conclusions are drawn. First, the FDA's own policies on informed consent require prompter public disclosure of adverse events. Second, the coupling of gene therapy and xenotransplantation trials entails a conceptual mistake in the types of communities that are harmed by each therapy's related adverse events. Third, all clinical trials merit such public disclosure of adverse events, not only gene therapy and xenotransplantation trials.

Comparative nocebo effects in older patients enrolled in cancer therapeutic trials: Observations from a 446-patient cohort—NCCTG 97-24-51 and ACOSOG Z9001 (Alliance A151602).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21545-e21545
Author(s):  
Jennifer Le-Rademacher ◽  
Jared C. Foster ◽  
Josephine Louella Feliciano ◽  
Ajeet Gajra ◽  
Drew K. Seisler ◽  
...  
Keyword(s):  
Adverse Event ◽  
Cancer Therapy ◽  
Adverse Events ◽  
Older Patients ◽  
Nocebo Effect ◽  
Double Blind ◽  
Inert Substance ◽  
Therapeutic Trials ◽  
Nocebo Effects ◽  
Event Rates

e21545 Background: A nocebo is an inert substance that causes adverse events. Although previous studies have examined the favorably positive (placebo) effects of an inert substance, few studies have examined negative (nocebo) effects, particularly in older patients who sometimes experience frequent and severe adverse events from cancer therapy. Methods: This study focused on placebo/nocebo-exposed patients who participated in two double-blind, placebo-controlled, cancer therapeutic studies, namely, North Central Cancer Treatment Group (NCCTG) 97-24-51 and American College of Surgeons Oncology Group (ACOSOG) Z9001, with the goal of reporting comparative, age-based adverse event rates. Results: Among the 446 patients who received placebo/nocebo exclusively, 161 were 65 years of age or older at the time of respective trial entry; 5234 adverse events occurred. Unadjusted adverse event rates did not differ significantly between patients 65 years of age or older and those younger: rate ratio (99% confidence intervals (CI): 1.01 (0.47, 2.02) with similar findings for grade 2 or worse adverse events and for all symptom-driven adverse events (for example, pain, loss of appetite, anxiety). Adjustment for sex, ethnicity, baseline performance score, and trial resulted in no significant age-based rate differences in adverse event rates. Similar findings were observed with an age threshold of 70. Conclusions: A nocebo effect appears to occur irrespective of age. This observation suggests that adverse events should be taken no less seriously in older than in younger cancer patients and that education to manage patients’ expectations from cancer therapy might improve tolerability. [Table: see text]

scholarly journals The Challenge: Finding the Most Appropriate Statin and Dose for Each Patient

2021 ◽  
Vol 70 (6 Supplement) ◽  
Author(s):  
Lillo
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Cardiovascular Risk ◽  
Patient Education ◽  
Statin Therapy ◽  
Common Reason ◽  
Nocebo Effect ◽  
Statin Intolerance

KEY TAKEAWAYS • Discontinuing statin therapy results in increased cardiovascular risk. • The nocebo effect is a common reason for perceived statin intolerance. • Statin intolerance is much less commonly reported in clinical trials than in clinical practice, suggesting that patient education and other safeguards employed in clinical trials are important to include in clinical practice. • Several strategies are available that can enable continuation of statin therapy in patients who are truly statin-intolerant.

scholarly journals Trial in Progress: Real-World Safety and Effectiveness of Brentuximab Vedotin in Adults with CD30+ Lymphoma in China

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4552-4552
Author(s):  
Pengpeng Xu ◽  
Mingci Cai ◽  
Wendy Zhang ◽  
Wei Li Zhao
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Informed Consent ◽  
Survival Rate ◽  
Real World ◽  
Brentuximab Vedotin ◽  
Routine Clinical Practice ◽  
Inclusion Criteria ◽  
Real World Data

Abstract Background: Clinical trials have demonstrated the effectiveness of the CD30-targeted antibody-drug conjugate brentuximab vedotin (BV) for the treatment of classical Hodgkin lymphoma (HL) and non-Hodgkin lymphoma(e.g. ALCL, PTCL-NOS, AITL, CTCL and etc.). While clinical trials are critical for establishing efficacy, collection of real-world data outside of the controlled trial setting is important to evaluate how interventions are applied and assess the effectiveness of new treatments in routine clinical practice. Inclusion criteria are often rather restrictive compared with the patient populations seen by physicians in daily practice. There are limited real-world data related to treatment with BV in China. Our study aims to obtain timely real-world knowledge in terms of safety and effectiveness of BV in CD30+ lymphoma patients in China. Study Design and Methods: The study (NCT04837222) is a real-world, prospective, multicenter study to evaluate the safety and effectiveness of BV in patients with CD30+ lymphoma in China. Consecutive CD30+ lymphoma patients treated with BV as a part of standard clinical practice will be enrolled. Key inclusion criteria includes adult patients undergoing treatment with BV or to be received with BV, patient/legal guardian must be able to read, understand, and sign the Informed Consent Form, CD30+ lymphoma by INV (any CD30 expression). Exclusion criteria includes patient who currently participates in or with plan to participate in any interventional clinical trial, any other reason that, in the investigator's opinion, makes the patient unsuitable to participate in this study. As CD30+ lymphoma is not a common disease and the affordability of novel treatment is limited, 1000 patients with CD30+ lymphoma will be recruited from almost 30 hematology centers. The physician will determine the treatment regimen, as well as the frequency of laboratory and clinical assessment according to her/his routine practice. All patients will be followed up per routine clinical practice and data will be documented at baseline/3/6/9/12/18/24 months unless withdrawal of Informed Consent, death or loss of follow-up, whichever comes first. Loss to follow-up will be minimized through active contact with participating patients thereafter to ensure almost all clinically relevant outcomes will be captured. The primary endpoint is serious adverse events. Secondary endpoints include adverse events, adverse drug reaction, dose adjustment, characteristics of patients receiving BV, use of BV, number of BV cycles administered, disease characteristics, time to next treatment, overall response rate, duration of response, progression free survival rate, overall survival rate, quality of life and cost-effectiveness ratio. Descriptive analysis will be performed for data analysis. Disclosures Zhang: Takeda Pharmaceuticals: Current Employment.

scholarly journals Evaluation of an enhanced training package to support clinical trials training in low and middle income countries (LMICs): experiences from the Born Too Soon Optimising Nutrition study

2021 ◽  
Author(s):  
Eleanor Jane Mitchell ◽  
Jalemba Aluvaala ◽  
Lucy Bradshaw ◽  
Jane P Daniels ◽  
Ashok Kumar ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Informed Consent ◽  
Global Health ◽  
Good Clinical Practice ◽  
Research Experience ◽  
Middle Income ◽  
Middle Income Countries ◽  
Training Package

Abstract Background Training is essential before working on a clinical trial, yet there is limited evidence on effective training methods. In low and middle income countries (LMICs), training of research staff was considered the second highest priority in a global health methodological research priority setting exercise. Methods We explored whether an enhanced training package in a neonatal feasibility study in Kenya and India, utilising elements of the train-the-trainer approach, altered clinicians and researchers’ clinical trials knowledge. A lead “trainer” was identified at each site who attended a UK-based introductory course on clinical trials. A two-day in-country training session was conducted at each hospital. Sessions included the study protocol, governance, data collection and ICH-Good Clinical Practice (GCP). To assess effectiveness of the training package, participants completed questionnaires at the start and end of the study period, including demographics, prior research experience, protocol-specific questions, informed consent and ICH-GCP. Results Thirty participants attended in-country training sessions and completed baseline questionnaires. Around three quarters had previously worked on a research study, yet only half had previously received training. Nineteen participants completed questionnaires at the end of the study period. Questionnaire scores were higher at the end of the study period, though not significantly so. Few participants ‘passed’ the informed consent and ICH-Good Clinical Practice (GCP) modules, using the Global Health Network Training Centre pass mark of ≥ 80%. Participants who reported having prior research experience scored higher in questionnaires before the start of the study period. Conclusions An enhanced training package can improve knowledge of research methods and governance though only small improvements in mean scores between questionnaires completed before and at the end of the study period were seen and were not statistically significant. This is the first report evaluating a clinical trial training package in a neonatal trial in LMICs. Due to the Covid-19 pandemic, research activity was paused and there was a significant time lapse between training and start of the study, which likely impacted upon the scores reported here. Given the burden of disease in LMICs, developing high-quality training materials which utilise a variety of approaches and build research capacity, is critical.

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