Informed consent for next-generation nucleotide sequencing studies: Aiding communication between participants and investigators.
ABSTRACT: Obtaining informed consent from prospective participants for research studies that include next-generation nucleotide sequencing (NGS) presents significant challenges because of the need to explain all the potential implications of participating, including the possible return of "incidental" findings, in easy-to-understand language.After reviewing the consent processes at other institutions, we decided to supplement the protocol-specific informed consent form with the following: (1) a short pamphlet for the prospective participant that includes a series of questions that she or he is encouraged to ask the investigator, and (2) a more detailed companion guide for investigators to help them develop simple-language answers to the questions. Both documents are available to use or modify.We propose an approach to obtaining informed consent for NGS studies that encourages discussion of key issues without creating a complex, comprehensive document for participants; it also maximizes investigator flexibility. We also suggest mechanisms to return restricted information to participants.
Project description:BACKGROUND:In clinical research, obtaining informed consent from participants is an ethical and legal requirement. Conveying the information concerning the study can be done using multiple methods yet this step commonly relies exclusively on the informed consent form alone. While this is legal, it does not ensure the participant's true comprehension. New effective methods of conveying consent information should be tested. In this study we compared the effect of different methods on the knowledge of caregivers of participants of a clinical trial on Pemba Island, Tanzania. METHODS:A total of 254 caregivers were assigned to receive (i) a pamphlet (n?=?63), (ii) an oral information session (n?=?62) or (iii) a pamphlet and an oral information session (n?=?64) about the clinical trial procedures, their rights, benefits and potential risks. Their post-intervention knowledge was assessed using a questionnaire. One group of caregivers had not received any information when they were interviewed (n?=?65). RESULTS:In contrast to the pamphlet, attending an information session significantly increased caregivers' knowledge for some of the questions. Most of these questions were either related to the parasite (hookworm) or to the trial design (study procedures). CONCLUSIONS:In conclusion, within our trial on Pemba Island, a pamphlet was found to not be a good form of conveying clinical trial information while an oral information session improved knowledge. Not all caregivers attending an information session responded correctly to all questions; therefore, better forms of communicating information need to be found to achieve a truly informed consent.
Project description:High-throughput nucleotide sequencing (often referred to as next-generation sequencing; NGS) is increasingly being chosen as a diagnostic tool for cases of expected but unresolved genetic origin. When exploring a higher number of genetic variants, there is a higher chance of detecting unsolicited findings. The consequential increased need for decisions on disclosure of these unsolicited findings poses a challenge for the informed consent procedure. This article discusses the ethical and practical dilemmas encountered when contemplating informed consent for NGS in diagnostics from a multidisciplinary point of view. By exploring recent similar experiences with unsolicited findings in other settings, an attempt is made to describe what can be learned so far for implementing NGS in standard genetic diagnostics. The article concludes with a set of points to consider in order to guide decision-making on the extent of return of results in relation to the mode of informed consent. We hereby aim to provide a sound basis for developing guidelines for optimizing the informed consent procedure.
Project description:OBJECTIVES:This study investigated how the essential elements of informed consent are realised during the consent process and examined the challenges in obtaining genuine informed consent in Korea. METHODS:Through purposive sampling, we recruited 21 subjects from those participating in anticancer drug research since 2013. We undertook 1:1 in-depth interviews and analysed the data by framework analysis. RESULTS:Themes raised throughout the interviews were categorised into 'disclosure' and 'understanding' of clinical information and 'decision'. Provider-centred information, both verbal and written, was delivered to each participant. There were few tools that the research staff might evaluate study participants' level of understanding of the provided information during the clinical trial. Although participants did not understand basic clinical trial concepts as much as desired, they may not seek to solve difficulties through communication with trial researchers. Doubts were raised about whether participants had sufficient capacity and free will to provide informed consent. CONCLUSION:There is a concern that informed consent can fall short of genuine in Korea. To ensure informed consent meets the international standard, greater efforts should be made to establish an explicit standard operational protocol for obtaining informed consent.
Project description:OBJECTIVE:To determine whether the manner of consent, i.e., informed consent by patients themselves or informed consent by proxy, affects clinical characteristics of samples of acute stroke patients enrolled in clinical trials. METHODS:We analyzed the manner of obtaining informed consent in the first 1,005 patients from WAKE-UP, an investigator-initiated, randomized, placebo-controlled trial of MRI-based thrombolysis in stroke patients with unknown time of symptom onset running in 6 European countries. Patients providing informed consent by themselves were compared with patients enrolled by proxy consent. Baseline clinical measures were compared between groups. RESULTS:In 359 (35.7%) patients, informed consent was by proxy. Patients with proxy consent were older (median 71 vs 66 years, p < 0.0001) and had a higher frequency of arterial hypertension (58.2% vs 43.4%, p < 0.0001). They showed higher scores on the NIH Stroke Scale (median 11 vs 5, p < 0.0001) and more frequently aphasia (73.7% vs 20.0%, p < 0.0001). The rate of proxy consent varied among countries (p < 0.0001), ranging from 77.1% in Spain to 1.2% in Denmark. CONCLUSIONS:Patients recruited by proxy consent were older, had more severe strokes, and had higher prevalence of aphasia than those with capacity to give personal consent. Variations in the manner of consent across countries may influence trial results. CLINICALTRIALSGOV AND CLINICALTRIALSREGISTEREU IDENTIFIERS:NCT01525290 (clinicaltrials.gov); 2011-005906-32 (clinicaltrialsregister.eu).
Project description:BACKGROUND:In Edinburgh, Scotland, lower influenza vaccine uptake has been observed in primary school children in the Polish community. METHODS:To address this disparity, the Polish-language version of the NHS Health Scotland influenza information pamphlet was updated and distributed in 2018 to all identified Polish pupils attending three pilot schools. The impact of the revised pamphlet was evaluated by examining changes in vaccine uptake in these schools as compared to a control group of schools, and a questionnaire was issued to all Polish parents in the pilot schools to explore their opinions of the pamphlet and preferred sources of immunisation information. RESULTS:On average uptake was 7.4% (95% CI 1.0-13.8%, p <?0.05) higher in the three pilot schools in which the Polish-language pamphlet was distributed (28.7%) than control schools (21.3%). The questionnaire feedback was that 37.3% of respondents felt better-informed about the influenza vaccine following the pamphlet. The respondents reported that the most important information source in deciding whether to vaccinate is previous experience. Healthcare professionals were ranked lower in importance when making a decision. Parents, who refused consent (n =?65) were more likely to source information from social media, friends and family, and Polish websites compared with those who consented (n =?45). CONCLUSIONS:These findings suggest that issuing new Polish health literature was associated with a large increase in consent form return rate and a modest increase in uptake of the influenza vaccine by Polish pupils in the pilot schools. Social media and Polish websites were found to have a greater influence over Polish parents' decision to immunise than UK healthcare staff and health authority information. Intensive effort is required to encourage parents towards information sources where more accurate pro-vaccination messages can be promulgated by national health services and independent expert groups. The role of social media for migrant communities requires careful consideration, especially for vaccine programmes not delivered in their country of birth.
Project description:Informed consent process is the cornerstone of ethics in clinical research. Obtaining informed consent from patients participating in clinical research is an important legal and ethical imperative for clinical trial researchers. Although informed consent is an important process in clinical research, its effectiveness and validity are always a concern. Issues related to understanding, comprehension, competence, and voluntariness of clinical trial participants may adversely affect the informed consent process. Communication of highly technical, complex, and specialized clinical trial information to participants with limited literacy, diverse sociocultural background, diminished autonomy, and debilitating diseases is a difficult task for clinical researchers. It is therefore essential to investigate and adopt innovative communication strategies to enhance understanding of clinical trial information among participants. This review article visits the challenges that affect the informed consent process and explores various innovative strategies to enhance the consent process.
Project description:BACKGROUND:Informed consent is among the biggest challenges in recruiting participants for clinical research studies. Researchers face many challenges in conducting clinical trials, some of which include budgetary restrictions, lack of trained personnel, and difficulty recruiting study participants-particularly minorities and participants from rural communities. OBJECTIVE:The objective of this study is to utilize telemedicine to improve the informed consent process for clinical trials and studies. We aim to assess the feasibility and efficacy of the teleconsent intervention among residents in urban and rural settings. METHODS:This study will be conducted separately yet concurrently at two institutions, the Medical University of South Carolina and the University of North Carolina at Chapel Hill, to compare results within and across institutions. RESULTS:Enrollment for Phase 1 began in March of 2018 and concluded in May 2018. Data transcription and analysis will be conducted through June and September of 2018. CONCLUSIONS:In this paper, we present a novel approach for conducting informed consent using a new telemedicine modality, namely, teleconsent. Teleconsent presents the ability to conduct a live interaction among clinical research coordinators and potential participants while synchronously presenting the consent form on the screen and obtaining participant's signature through doxy.me, the teleconsent system. Teleconsent provides potential to improve obtaining informed consent from potential clinical trial participants. REGISTERED REPORT IDENTIFIER:RR1-10.2196/11239.
Project description:Introduction:Obtaining informed consent from study participants and disseminating the findings responsibly is a key principle required for ethically conducted clinical and genetic research. Reports from African researchers providing feedback on insights gained during the return of whole exome sequencing (WES) results to breast cancer patients treated in resource-limited settings is lacking. Aim:The empirical process used to fill this gap in relation to BRCA1/2 variant detection using WES provided unique insights incorporated into a pathology-supported genetic testing algorithm for return of research results to Kenyan breast cancer patients. Methods:The Informed consent form approved by the Moi Teaching and Referral Hospital in Kenya was adopted from a translational research study conducted in South Africa. Initially, the informed consent process was piloted in 16 Kenyan female patients referred for breast surgery, following a community-based awareness campaign. A total of 95 female and two male breast cancer patients were enrolled in the study from 2013 to 2016. Immunohistochemistry (IHC) results of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) status were obtained from hospital records. DNA of patients with a family history of cancer was extracted from saliva and screened for pathogenic variants in the BRCA1/2 genes as the first step using WES. Results:Ten patients approached for participation in this study declined to sign the informed consent form. Data on IHC used as a proxy for molecular subtype were available in 8 of 13 breast cancer patients (62%) with a family history of cancer. Five BRCA1/2 variants of uncertain clinical significance were detected, as well as a pathogenic BRCA2 variant (c.5159C > A; S1720?) in a female patient eligible for return of WES results. Conclusion:Experience gained during the qualitative pilot phase was essential to overcome challenges associated with the translation of sophisticated genetic terms into native African languages. Detection of a pathogenic BRCA2 variant in a patient with familial breast cancer, frequently associated with hormone receptor-positive breast carcinoma as reported in this case, led to a high level of confidence on which to base risk management in future. Implementation of new technologies alongside standard pathology provides a practical approach to the application of genomic medicine in Africa.
Project description:BACKGROUND AND PURPOSE:No standard approach to obtaining informed consent for stroke thrombolysis with tPA (tissue-type plasminogen activator) currently exists. We aimed to assess current nationwide practice patterns of obtaining informed consent for tPA. METHODS:An online survey was developed and distributed by e-mail to clinicians involved in acute stroke care. Multivariable logistic regression analyses were performed to determine independent factors contributing to always obtaining informed consent for tPA. RESULTS:Among 268 respondents, 36.7% reported always obtaining informed consent and 51.8% reported the informed consent process caused treatment delays. Being an emergency medicine physician (odds ratio, 5.8; 95% confidence interval, 2.9-11.5) and practicing at a nonacademic medical center (odds ratio, 2.1; 95% confidence interval, 1.0-4.3) were independently associated with always requiring informed consent. The most commonly cited cause of delay was waiting for a patient's family to reach consensus about treatment. CONCLUSIONS:Most clinicians always or often require informed consent for stroke thrombolysis. Future research should focus on standardizing content and delivery of tPA information to reduce delays.
Project description:Background Informed consent is often cited as the “cornerstone” of research ethics. Its intent is that participants enter research voluntarily, with an understanding of what their participation entails. Despite agreement on the necessity to obtain informed consent in research, opinions vary on the threshold of disclosure necessary and the best method to obtain consent. We aimed to investigate Australian researchers’ views on, and their experiences with, obtaining informed consent. Methods Semi-structured interviews were conducted with 23 researchers from NSW institutions, working in various fields of research. Interviews were analysed and coded to identify themes. Results Researchers reported that consent involved information disclosure, understanding and a voluntary decision. They emphasised the variability of consent interactions, which were dependent on potential participants’ abilities and interests, study complexity and context. All researchers reported providing written information to potential participants, yet questioned the readability and utility of this information. The majority reported using signed consent forms to ‘operationalise’ consent and reported little awareness of, and lack of support in implementing more dynamic informed consent procedures, such as verbal informed consent, that was fit for the purposes of their studies. Views on Human Research Ethics Committees (HRECs) varied. Some reported inconsistent, arduous inputs on the information form and consent process. Others expressed reliance on HRECs for guidance, viewing them as institutional safeguards. Conclusions This study highlights the importance of transparent relationships, both between researchers and participants, and between researchers and HRECs. Where the relationship with study participants was reported as more robust, researchers felt that they were better able to ensure participants made better, more informed decisions. Where the relationship with HRECs was reported as more robust, researchers were more likely to view them as institutional safeguards, rather than as bureaucratic hindrances. Conscientious and mindful researchers are paramount to ensuring the procedure accommodates individual requirements. This study advocates that when designing ethical informed consent practices, researchers should be integrated as autonomous players with a positive input on the process, rather than, in the worst case, predatory recruiters to be curtailed by information forms and oversight.