Developing guidance for pregnancy testing of adolescents participating in research: ethical, legal and practical considerations

2016 ◽  
Vol 101 (10) ◽  
pp. 980-983 ◽  
Author(s):  
Vic Larcher ◽  
Joe Brierley

Adolescents need safe effective drugs that have undergone ethically approved testing in clinical trials; such studies often require pregnancy testing in ‘women of childbearing age’ which includes children/adolescents. There is a lack of consistent standard operating procedures for pregnancy testing in these individuals, in either research or clinical (ie, both preprocedure and clinical emergency) settings. Some harmonisation between a selective or universal testing approach based on a risk analysis of the trial drug or procedure would seem sensible. The need for pregnancy testing and the reasons for the method chosen (universal or selective) should be clearly defined in the research protocol. Research ethics committees (RECs) need to satisfy themselves that the selection of subjects to be tested, the procedures for obtaining consent and the respecting of the young person's confidentiality are appropriate and that management of any positive tests are in accord with local safeguarding policies and procedures. Researchers should have core competencies necessary to manage sensitive questioning and child safeguarding training. Clinical trials of medicinal product (CTIMP) pregnancy testing in females 13–15 years of age requires parental consent and the child's active involvement in the decision-making process (‘assent’) the implications of a positive test should be discussed in advance. Children under 13 years should not normally be subject to pregnancy testing in CTIMPs, unless there are exceptional circumstances, for example, a trial of contraceptive agents of a high teratogenicity risk, as reviewed by a specialist paediatric REC. We analyse the ethical, legal and practical aspects of this issues and supply guidance to support those involved.

2020 ◽  
Vol 16 (3-4) ◽  
pp. 1-10 ◽  
Author(s):  
Francois Bompart

Hundreds of clinical trials of potential treatments and vaccines for the “coronavirus 19 disease” (COVID-19) have been set up in record time. This is a remarkable reaction to the global pandemic, but the absence of a global coordination of clinical research efforts raises serious ethical concerns. Some COVID-19 patients might carry the burden of clinical trial involvement even though their trial cannot be completed as researchers are competing for patients. A shortage of medicines can occur when existing drugs are diverted for clinical trials. Research ethics committees are overburdened with multiple applications. A multitude of trials can also overstretch medical staff and risk neglecting non-COVID-19 patients. And finally, conflicting conclusions from a multitude of heterogeneous trials might lead to delays in public health decisions about life-saving issues. These challenges are made worse by the unpredictable evolution of epidemics, the active involvement of political decision-makers in scientific issues and the pressure of social media globally. While freedom to conduct research must be safeguarded, global health emergency situations would greatly benefit from effective international coordination mechanisms for clinical research.


2020 ◽  
Author(s):  
Lida Feyz ◽  
Yale Wang ◽  
Atul Pathak ◽  
Manish Saxena ◽  
Felix Mahfoud ◽  
...  

BACKGROUND Great and costly efforts are required to recruit potential participants into clinical trials. Using social media may make the recruitment process more efficient. Merely 20% of clinical trials are completed on time, a finding mostly linked to challenges in patient recruitment [1]. Recruitment through social media is increasingly being recognized as a tool to efficiently identify eligible subjects at lower costs [2, 3]. One of the key reasons for its success is the strong adherence of users to specific social media platforms. Facebook for instance has over 2.38 billion active monthly users of which about 75% access the network on a daily basis [4]. As such, the platform and other like it offer great potential to quickly and affordably enroll patients into clinical trials and surveys [3, 5-7]. At present, little evidence is available on the efficacy of using social media to recruit patients into cardiovascular and hypertension trials [8]. The aim of the present study was to evaluate the efficacy of social media as an approach to recruit hypertensive patients into the RADIANCE-HTN SOLO trial. OBJECTIVE The aim of the present study was to evaluate the efficacy of social media as an approach to recruit hypertensive patients into the RADIANCE-HTN SOLO trial. METHODS The RADIANCE-HTN SOLO (NCT02649426) is a multicenter, randomised study that was designed to demonstrate the efficacy and safety of endovascular ultrasound renal denervation (RDN) to reduce ambulatory blood pressure at 2 months in patients with combined systolic–diastolic hypertension in the absence of medications. Between March 28, 2016, and Dec 28, 2017, 803 patients were screened for eligibility and 146 were randomised to undergo RDN (n=74) or a sham procedure (n=72) [9]. Key entry criteria included: age 18-75 years with essential hypertension using 0-2 antihypertensive drugs. Patients were recruited from 21 hospitals in the USA and 18 hospitals in Europe. The study was approved by local ethics committees or institutional review boards and was performed in accordance with the declaration of Helsinki. All participants provided written informed consent. All recruitment materials including social media campaigns was approved by local ethics committees of the involved sites. Recruitment strategies included social media (Facebook), conventional advertisements (ads) (magazine, brochure/poster, radio, newspaper), web search (the clinical website, craigslist and web-browsing), and physician referral. Both newspaper ads and posters contained brief information about study entry criteria. Newspapers were distributed at public transport places and posters were displayed in outpatient cardiology and hypertension clinics. Radio ads were run for 30 or 60 seconds providing a short summary of the study, entry criteria and contact information. Ads were run in major metropolitan areas on radio stations with large adult listener bases during popular days and times. Facebook ads were targeted towards subjects >45 years old within a certain distance from a recruitment site (range 20-50 miles). Criteria were modified over time in order to increase response rates [i.e. distance was increased or decreased, age was increased to >55 year]. Facebook ads referred to a dedicated study website translated into country specific languages. If interested, subjects could complete an anonymous online screening questionnaire which provided direct automatic feedback on study eligibility. Eligible subjects were asked to provide contact details (name and telephone number) to receive additional information, a process coordinated via a secure online portal (Galen Gateway Patient Recruitment Portal, Galen Patient Recruitment, Inc., Cumberland, RI). Study site were only able to contact potential candidates within their area. The study sponsor was not able to access any personal data. Trained local site personnel or contracted secondary screeners contacted candidates by phone to verify eligibility and answer potential questions. A subsequent outpatient clinic visit was scheduled during which the study was explained in greater detail and the informed consent form could be signed. Statistical analysis Categorical variables were expressed as percentages and counts. Continuous variables were described as mean  standard deviation (SD) when normally distributed, data was compared using an Independent-Samples or Paired-Samples T test to analyze the difference between recruitment methods. In case of non-normal distribution, median data was presented with the interquartile range [IQR]. All statistical tests are 2-tailed. A P-value <0.05 was considered statistically significant. Statistical analysis was performed using SPSS statistical analysis (version 24.0).   RESULTS Results Facebook ads were active during a 115-day recruitment period between August and November 2017. A total of 285 potential candidates were recruited by different recruitment strategies in this specific time period, of which 184 (65%) were consented through Facebook (Table 1). The average age of the subjects consented through Facebook was 59 ± 8 years and 51% were male (Table 2). Facebook reached 5.3 million people in 168 separate campaigns run in proximity to 19 sites in the US and 14 sites in Europe. The number of candidates per site was variable with a median of 23 [17 – 26] candidates per site that passed the questionnaire (Figure 1). A total of 27/184 subjects were eventually randomised. Total cost for the Facebook ads was $152,412; costing $907/campaign and $0.83/click. This resulted in a total cost of $828/consent. During the same recruitment period, 7-day radio spots were launched with a total cost of $2,870; resulting in 9 inquiries with eventually 5 potential candidates and 2 consents ($1,435/consent).   CONCLUSIONS Conclusion Targeted social media was a successful and efficient strategy to find potential candidates for a multicenter blood pressure clinical trial. Whether this approach can be replicated across other disease states or demographics remains to be studied.


2020 ◽  
Vol 47 (1) ◽  
pp. 7-11
Author(s):  
Maud O. Jansen ◽  
Peter Angelos ◽  
Stephen J. Schrantz ◽  
Jessica S. Donington ◽  
Maria Lucia L. Madariaga ◽  
...  

Clinical trials emerged in rapid succession as the COVID-19 pandemic created an unprecedented need for life-saving therapies. Fair and equitable subject selection in clinical trials offering investigational therapies ought to be an urgent moral concern. Subject selection determines the distribution of risks and benefits, and impacts the applicability of the study results for the larger population. While Research Ethics Committees monitor fair subject selection within each trial, no standard oversight exists for subject selection across multiple trials for the same disease. Drawing on the experience of multiple clinical trials at a single academic medical centre in the USA, we posit that concurrent COVID-19 trials are liable to unfair and inequitable subject selection on account of scientific uncertainty, lack of transparency, scarcity and, lastly, structural barriers to equity compounded by implicit bias. To address the critical gap in the current literature and international regulation, we propose new ethical guidelines for research design and conduct that bolsters fair and equitable subject selection. Although the proposed guidelines are tailored to the research design and protocol of concurrent trials in the COVID-19 pandemic, they may have broader relevance to single COVID-19 trials.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 815
Author(s):  
Bárbara Costa ◽  
Nuno Vale

The pandemic of the coronavirus disease 2019 (COVID-19) represents an unprecedented challenge to identify effective drugs for prevention and treatment. While the world’s attention is focused on news of COVID-19 vaccine updates, clinical management still requires improvement. Due to the similarity of cancer-induced inflammation, immune dysfunction, and coagulopathy to COVID-19, anticancer drugs, such as Interferon, Pembrolizumab or Bicalutamide, are already being tested in clinical trials for repurposing, alone or in combination. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected, clinicians need effective medical treatments for this infection.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenjing Guo ◽  
Bohu Pan ◽  
Sugunadevi Sakkiah ◽  
Zuowei Ji ◽  
Gokhan Yavas ◽  
...  

AbstractCoronavirus disease 2019 (COVID-19) is an ongoing pandemic and there is an urgent need for safe and effective drugs for COVID-19 treatment. Since developing a new drug is time consuming, many approved or investigational drugs have been repurposed for COVID-19 treatment in clinical trials. Therefore, selection of safe drugs for COVID-19 patients is vital for combating this pandemic. Our goal was to evaluate the safety concerns of drugs by analyzing adverse events reported in post-market surveillance. We collected 296 drugs that have been evaluated in clinical trials for COVID-19 and identified 28,597,464 associated adverse events at the system organ classes (SOCs) level in the FDA adverse events report systems (FAERS). We calculated Z-scores of SOCs that statistically quantify the relative frequency of adverse events of drugs in FAERS to quantitatively measure safety concerns for the drugs. Analyzing the Z-scores revealed that these drugs are associated with different significantly frequent adverse events. Our results suggest that this safety concern metric may serve as a tool to inform selection of drugs with favorable safety profiles for COVID-19 patients in clinical practices. Caution is advised when administering drugs with high Z-scores to patients who are vulnerable to associated adverse events.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Daria Kim ◽  
Joerg Hasford

Abstract The problem of wasteful clinical trials has been debated relentlessly in the medical community. To a significant extent, it is attributed to redundant trials – studies that are carried out to address questions, which can be answered satisfactorily on the basis of existing knowledge and accessible evidence from prior research. This article presents the first evaluation of the potential of the EU Clinical Trials Regulation 536/2014, which entered into force in 2014 but is expected to become applicable at the end of 2021, to prevent such trials. Having reviewed provisions related to the trial authorisation, we propose how certain regulatory requirements for the assessment of trial applications can and should be interpreted and applied by national research ethics committees and other relevant authorities in order to avoid redundant trials and, most importantly, preclude the unnecessary recruitment of trial participants and their unjustified exposure to health risks.


2021 ◽  
Vol 11 ◽  
Author(s):  
Osmel Companioni ◽  
Cristina Mir ◽  
Yoelsis Garcia-Mayea ◽  
Matilde E. LLeonart

Sphingolipids are an extensive class of lipids with different functions in the cell, ranging from proliferation to cell death. Sphingolipids are modified in multiple cancers and are responsible for tumor proliferation, progression, and metastasis. Several inhibitors or activators of sphingolipid signaling, such as fenretinide, safingol, ABC294640, ceramide nanoliposomes (CNLs), SKI-II, α-galactosylceramide, fingolimod, and sonepcizumab, have been described. The objective of this review was to analyze the results from preclinical and clinical trials of these drugs for the treatment of cancer. Sphingolipid-targeting drugs have been tested alone or in combination with chemotherapy, exhibiting antitumor activity alone and in synergism with chemotherapy in vitro and in vivo. As a consequence of treatments, the most frequent mechanism of cell death is apoptosis, followed by autophagy. Aslthough all these drugs have produced good results in preclinical studies of multiple cancers, the outcomes of clinical trials have not been similar. The most effective drugs are fenretinide and α-galactosylceramide (α-GalCer). In contrast, minor adverse effects restricted to a few subjects and hepatic toxicity have been observed in clinical trials of ABC294640 and safingol, respectively. In the case of CNLs, SKI-II, fingolimod and sonepcizumab there are some limitations and absence of enough clinical studies to demonstrate a benefit. The effectiveness or lack of a major therapeutic effect of sphingolipid modulation by some drugs as a cancer therapy and other aspects related to their mechanism of action are discussed in this review.


2008 ◽  
Vol 15 (2) ◽  
pp. 183-195
Author(s):  
Valerie Junod

AbstractMedical research on minors entails both risks and benefits. Under Swiss law, clinical trials on children, including nontherapeutic drug trials, are permissible. However, ethics committees must systematically verify that all clinical studies have a favorable risk-benefit profile. Additional safeguards are designed to ensure that children are not unnecessarily involved in research and that proper consent is always obtained. Federal Swiss law is undergoing revision to extend these protections beyond clinical trials to a broad array of health research. The Swiss drug agency also seeks to improve the incentives for pharmaceutical firms to develop new paediatric drugs and relevant paediatric drug labels.


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