scholarly journals Nocebo effects and participant information leaflets: evaluating information provided on adverse effects in UK clinical trials

2020 ◽  
Author(s):  
Nigel Kirby ◽  
Victoria Shepherd ◽  
Jeremy Howick ◽  
Sophie Betteridge ◽  
Kerenza Hood
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Adverse Events ◽  
Medicinal Products ◽  
Flesch Reading Ease ◽  
Information Leaflets ◽  
Potential Benefits ◽  
Nocebo Effects ◽  
Trial Participants ◽  
Participant Information

Abstract Background Nocebo effects (‘negative placebo’ effects) experienced by clinical trial participants can arise from an underlying condition or through communication about side effects in the participant information leaflets (or elsewhere). However, little is known about how information on potential side effects is provided to trial participants. In this study we aimed to increase the evidence-base in this area by identifying the way in which potential side effects from investigational medicinal products used in trials are presented in written information to potential participants. Methods Trials were identified from the International Standard Randomised Controlled Trials Number (ISRCTN) clinical trial registry. Eligible studies were placebo controlled clinical trials of investigational medicinal products (IMP) in adults conducted in the UK in three targeted clinical areas (cancer, musculoskeletal conditions and mental and behavioural disorders). Ongoing and recently completed (within three years) trials were included. We assessed readability using the Flesch Reading Ease scale, Gunning-Fog Index and Flesch-Kincaid Grade. Data extracted from the PILs were divided into 8 predefined qualitative themes for analysis in NVivo11. Results PILs from 33 studies were included. Most of the patient information leaflets were ranked as ‘fairly easy to read’ or ‘difficult to read’ according to the Flesch Reading Ease scale. All studies presented information about adverse events, whereas only a third presented information about intervention benefits. Where intervention or study benefits were presented, they were usually after adverse events (21/33 64%). Discussion Participant information leaflets scored poorly on ease of readability and had more content relating to adverse effects than any potential beneficial effects. The way in which adverse events were presented was heterogeneous in terms of their likelihood and severity and the amount and level of detail provided. In comparison to the adverse effects, potential benefits from the intervention and/or study were described less often and by shorter text. Participants were commonly presented with adverse effects ahead of any potential benefits.

scholarly journals Nocebo effects and participant information leaflets: evaluating information provided on adverse effects in UK clinical trials

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Nigel Kirby ◽  
Victoria Shepherd ◽  
Jeremey Howick ◽  
Sophie Betteridge ◽  
Kerenza Hood
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Information Leaflets ◽  
Nocebo Effects ◽  
Participant Information

scholarly journals An analysis of potential costs of adverse events based on Drug Programs in Poland. Pulmonology focus

2014 ◽  
Vol 27 (1) ◽  
pp. 32-36
Author(s):  
Monika Szkultecka-Debek ◽  
Mariola Drozd ◽  
Karina Jahnz-Rozyk ◽  
Nina Kiepurska ◽  
Joanna Mazurek ◽  
...  
Keyword(s):  
Side Effects ◽  
Adverse Events ◽  
Medicinal Products ◽  
Disease Area ◽  
Significant Cost ◽  
The Public ◽  
Polish Society ◽  
Costs Of Treatment ◽  
The Common ◽  
Public Payer

Abstract The project was performed within the Polish Society for Pharmacoeconomics (PTFE). The objective was to estimate the potential costs of treatment of side effects, which theoretically may occur as a result of treatment of selected diseases. We analyzed the Drug Programs financed by National Health Fund in Poland in 2012 and for the first analysis we selected those Programs where the same medicinal products were used. We based the adverse events selection on the Summary of Product Characteristics of the chosen products. We extracted all the potential adverse events defined as frequent and very frequent, grouping them according to therapeutic areas. This paper is related to the results in the pulmonology area. The events described as very common had an incidence of ≥ 1/10, and the common ones ≥ 1/100, <1/10. In order to identify the resources used, we performed a survey with the engagement of clinical experts. On the basis of the collected data we allocated direct costs incurred by the public payer. We used the costs valid in December 2013. The paper presents the estimated costs of treatment of side effects related to the pulmonology disease area. Taking into account the costs incurred by the NHF and the patient separately e calculated the total spending and the percentage of each component cost in detail. The treatment of adverse drug reactions generates a significant cost incurred by both the public payer and the patient.

scholarly journals Adverse effects of adjuvant endocrine therapy

2018 ◽  
pp. 64-69
Author(s):  
E. I. Kovalenko ◽  
I. B. Kononenko ◽  
A. V. Snegovoi ◽  
O. P. Grebennikova ◽  
L. V. Manzyuk
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Side Effects ◽  
Adverse Effects ◽  
Adverse Events ◽  
Endocrine Therapy ◽  
Aromatase Inhibitors ◽  
Hormonal Therapy ◽  
Adjuvant Endocrine Therapy

Hormonal therapy is a highly effective and well tolerable treatment of hormone-responsive breast cancer. However, it has some side effects that can affect quality of life and lead to treatment discontinuation. Common side effects of tamoxifen and aromatase inhibitors are discussed in this article: menopausal, gynecological symptoms, cardiovascular and musculoskeletal adverse events. Some of them are preventable and manageable. In order to maintain good quality of life during treatment the oncologists should pay more attention to the side effects that lead to it’s deterioration and not be too anxious about insignificant ones.

scholarly journals The adverse effects of bisphosphonates in breast cancer: A systematic review and network meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246441
Author(s):  
Christopher Jackson ◽  
Alexandra L. J. Freeman ◽  
Zśofia Szlamka ◽  
David J. Spiegelhalter
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Adverse Effects ◽  
Adverse Events ◽  
Metastatic Cancer ◽  
Meta Analysis ◽  
Menopausal Status ◽  
Adverse Outcomes ◽  
Large Trial ◽  
Meta Analyses

Background Bisphosphonate drugs can be used to improve the outcomes of women with breast cancer. Whilst many meta-analyses have quantified their potential benefits for patients, attempts at comprehensive quantification of potential adverse effects have been limited. We undertook a meta-analysis with novel methodology to identify and quantify these adverse effects. Methods We systematically reviewed randomised controlled trials in breast cancer where at least one of the treatments was a bisphosphonate (zoledronic acid, ibandronate, pamidronate, alendronate or clodronate). Neoadjuvant, adjuvant and metastatic settings were examined. Primary outcomes were adverse events of any type or severity (excluding death). We carried out pairwise and network meta-analyses to estimate the size of any adverse effects potentially related to bisphosphonates. In order to ascertain whether adverse effects differed by individual factors such as age, or interacted with other common adjuvant breast cancer treatments, we examined individual-level patient data for one large trial, AZURE. Findings We identified 56 trials that reported adverse data, which included a total of 29,248 patients (18,301 receiving bisphosphonate drugs versus 10,947 not). 24 out of the 103 different adverse outcomes analysed showed a statistically and practically significant increase in patients receiving a bisphosphonate drug compared with those not (2 additional outcomes that appeared statistically significant came only from small studies with low event counts and no clinical suspicion so are likely artifacts). Most of these 24 are already clinically recognised: ‘flu-like symptoms, fever, headache and chills; increased bone pain, arthralgia, myalgia, back pain; cardiac events, thromboembolic events; hypocalcaemia and osteonecrosis of the jaw; as well as possibly stiffness and nausea. Oral clodronate appeared to increase the risk of vomiting and diarrhoea (which may also be increased by other bisphosphonates), and there may be some hepatotoxicity. Four additional potential adverse effects emerged for bisphosphonate drugs in this analysis which have not classically be recognised: fatigue, neurosensory problems, hypertonia/muscle spasms and possibly dysgeusia. Several symptoms previously reported as potential side effects in the literature were not significantly increased in this analysis: constipation, insomnia, respiratory problems, oedema or thirst/dry mouth. Individual patient-level data and subgroup analysis revealed little variation in side effects between women of different ages or menopausal status, those with metastatic versus non-metastatic cancer, or between women receiving different concurrent breast cancer therapies. Conclusions This meta-analysis has produced estimates for the absolute frequencies of a range of side effects significantly associated with bisphosphonate drugs when used by breast cancer patients. These results show good agreement with previous literature on the subject but are the first systematic quantification of side effects and their severities. However, the analysis is limited by the availability and quality of data on adverse events, and the potential for bias introduced by a lack of standards for reporting of such events. We therefore present a table of adverse effects for bisphosphonates, identified and quantified to the best of our ability from a large number of trials, which we hope can be used to improve the communication of the potential harms of these drugs to patients and their healthcare providers.

Use of Oral Methadone as an Analgesic: Review of the Cardiotoxic Side Effects

2010 ◽  
Vol 2 ◽  
pp. CMT.S3579
Author(s):  
Pramod Kumar
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Adverse Events ◽  
Oral Analgesic ◽  
Oral Methadone

Methadone is a synthetic opiate primarily used in the detoxification and maintenance of patients who are dependent on opiates particularly heroin. Though within last 10–15 years methadone is increasingly used to manage neuropathic and cancer pains. Unfortunately, with increased methadone use for pain is coincided with significant increase in adverse events and fatalities. Cardiotoxicity is one of the major adverse effects reported with the use of oral methadone. The purpose of this paper is to provide an overview of the cardiotoxicity of methadone, when used as an oral analgesic and protocols for safe prescribing of methadone to help physicians recognize situations where this drug offers the greatest advantage as an analgesic.

scholarly journals Adverse events with ayurvedic medicines- possible adulteration and some inherent toxicities

2019 ◽  
Vol 4 ◽  
pp. 23
Author(s):  
Buddhi Paudyal ◽  
Astha Thapa ◽  
Keshav Raj Sigdel ◽  
Sudeep Adhikari ◽  
Buddha Basnyat
Keyword(s):  
Rheumatoid Arthritis ◽  
Nephrotic Syndrome ◽  
Side Effects ◽  
Adverse Effects ◽  
Adverse Events ◽  
Indian Subcontinent ◽  
Ayurvedic Medicine ◽  
Gold Salt ◽  
Traditional System ◽  
Wide Range

Ayurvedic medicine, a traditional system of medicine practiced in the Indian subcontinent is considered to be devoid of adverse effects. We report three cases which highlight the possibility of adverse events related with the use ofwith the use of ayurvedic products. A 35 years old woman with hepatitis took ayurvedic powder medicine and with swarnabhasma (gold salt)s and had her liver injury worsened, possibly due to alkaloids, and developed nephrotic syndrome, possibly due to and gold salt. A 57 years old hypertensive man was taking ayurvedic medicine containing reserpine which had long been withdrawn from the allopathic system of medicine due to wide range of side effects. A 47 years old woman with rheumatoid arthritis was taking an unknown tablet containing a steroid as an adulterant for 2 years and developed side effects typical of steroid excess. We like to highlight the fact that ayurvedic medicines do have propensity to may cause adverse effects due to adulterations or inherent constituents like alkaloids, and hence are may not always be completely safe.

scholarly journals Adverse Events Profile of Low-dose Methotrexate in Nepalese Patients with Rheumatoid Arthritis: an Observational Study

2020 ◽  
Vol 18 (3) ◽  
pp. 360-365
Author(s):  
Shweta Nakarmi ◽  
Kalpana Pudasaini ◽  
Bhojraj Adhikari ◽  
Binit Vaidya
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Effect ◽  
Side Effects ◽  
Liver Function ◽  
Adverse Effects ◽  
Adverse Events ◽  
Observational Study ◽  
P Value ◽  
Function Tests ◽  
Patient Reported

Background: Methotrexate is considered as the anchor drug for the treatment of rheumatoid arthritis. However, various adverse effects limit its use leading to frequent discontinuation of treatment. This study aimed to evaluate the common adverse effects of methotrexate in patients with rheumatoid arthritis. Methods: A prospective observational study was conducted at National Center for Rheumatic Diseases from June 2018 to May 2019 among patients with rheumatoid arthritis using methotrexate monotherapy. Laboratory tests like liver function tests, renal function tests, complete blood count, C-reactive protein, erythrocyte sedimentation rate were done at baseline and every 3 months. Data on patients’ comorbidities, disease activity and side effects of drug were collected on every follow- up. Statistical analysis was carried out with the help of SPSS 23.0. Results: Out of 232 patients experiencing at least one adverse effect while on methotrexate monotherapy, 87.5% were female and mean age was 46.9±10.8 years. The mean dose of methotrexate was 16.6 ± 3.9 mg/week with the most frequently used dose of 20mg/week. Among the variety of adverse reaction observed, the most common was transaminitis (75.0%) with approximately 50.0% as isolated liver function abnormality, followed by nausea (19.4%), anorexia (12.9%), leukopenia (12.5%), oral ulcer (8.2%) and psychological intolerance (4.7%). Multiple regression analysis showed significant predictive value of body mass index for transaminitis (p-value 0.007). Conclusions: Asymptomatic liver function test derangement was the most frequent adverse-effect of methotrexate observed, whereas nausea and anorexia were the most common patient reported events. The frequent dose associated with side-effects in Nepalese patients was around 20mg/week. Keywords: Adverse events; methotrexate; Nepal; rheumatoid arthritis

scholarly journals Fatal and non-fatal adverse events of glucocorticoid therapy for Graves' orbitopathy: a questionnaire survey among members of the European Thyroid Association

2012 ◽  
Vol 166 (2) ◽  
pp. 247-253 ◽  
Author(s):  
Claudio Marcocci ◽  
Torquil Watt ◽  
Maria Antonietta Altea ◽  
Ase Krogh Rasmussen ◽  
Ulla Feldt-Rasmussen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Side Effects ◽  
Adverse Effects ◽  
Adverse Events ◽  
Cumulative Dose ◽  
Questionnaire Survey ◽  
Glucocorticoid Therapy ◽  
Cerebrovascular Complications ◽  
Graves Orbitopathy ◽  
Fatal Adverse Events

ObjectiveThe objective of this study was to investigate the side effects of glucocorticoid (GC) therapy observed by European thyroidologists during the treatment of Graves' orbitopathy (GO).DesignA questionnaire-based survey among members of the European Thyroid Association (ETA) who treat GO.ResultsA response was obtained from 128 ETA members of which 115 used GC therapy for GO. The majority of respondents (83/115, 72%) used intravenous (i.v.) GC, with a relatively wide variety of therapeutic regimens. The cumulative dose of methylprednisolone ranged between 0.5 and 12 g (median 4.5 g) for i.v.GC and between 1.0 and 4.9 g (median 2.4 g) for oral GC. Adverse events were often reported during oral GCs (26/32, 81%); most side effects were non-severe, but ten respondents reported severe adverse events (hepatic, cardiovascular, and cerebrovascular complications), including two fatal cases, both receiving a total of 2.3 g prednisone. Adverse events were less common in i.v.GC (32/83 respondents, 39%), but mostly consisted of severe events, including seven fatal cases. All but one fatal event occurred in cumulative i.v.GC doses (>8 g) higher than those currently recommended.ConclusionsGCs are preferentially administered i.v. for the treatment of GO in Europe. Both oral and i.v.GC may be associated with severe adverse effects, including fatal cases, which are more frequently reported in daily or alternate day i.v.GC. IvGC therapy should be undertaken in centers with appropriate expertise. Patients should be carefully examined for risk factors before treatment and monitored for side effects, which may be asymptomatic, both during and after treatment.

scholarly journals Relative importance of informational items in participant information leaflets for trials: a Q-methodology approach

BMJ Open ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. e023303 ◽  
Author(s):  
Karen Innes ◽  
Seonaidh Cotton ◽  
Marion K Campbell ◽  
Jim Elliott ◽  
Katie Gillies
Keyword(s):  
Q Methodology ◽  
Trial Participation ◽  
Sufficient Information ◽  
Think Aloud ◽  
Stakeholder Groups ◽  
Information Leaflets ◽  
Research Nurses ◽  
Trial Participants ◽  
Potential Trial ◽  
Participant Information

ObjectivesTo identify which information items potential participants and research nurses rank as the most important, and the reasons for this, when considering participation in a randomised controlled trial.DesignQ-methodology approach alongside a think-aloud process. Using a vignette outlining a hypothetical trial, participants were asked to rank statements about informational items usually included in a participant information leaflet (PIL) on a Q-grid, while undertaking a real-time think-aloud process to elicit the underpinning decision processes. Analysis of quantitative data was conducted using descriptive statistics and qualitative data was coded using content analysis.Participants20 participants (10 potential trial participants and 10 research nurses).SettingUK-based participants.ResultsTen research nurses and 10 potential trial participants provided data for the study. Both stakeholder groups ranked similar statements in their top three most important statements, with ‘What are the possible disadvantages and risks of taking part?’ featuring in both. However, considerable variability existed between the groups with regard to their ranking of statements of least importance. Participants identified that sufficient information to make a decision was secured using around 14 items. Participants also identified other items of importance not routinely included in PILs.ConclusionsThis study has provided a unique insight into how and why different trial stakeholder groups rank informational items currently contained within PILs. These results have implications for those developing future PILs and those who develop guidance on their content; PILs should focus most on the information items that potential trial participants want and need to make an informed choice about trial participation.

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