Generalisability and Cost-Impact of Antibiotic-Impregnated Central Venous Catheters for Reducing Risk of Bloodstream Infection in Paediatric Intensive Care Units in England

Background

We determined the generalisability and cost-impact of adopting antibiotic-impregnated CVCs in all paediatric intensive care units (PICUs) in England, based on results from a large randomised controlled trial (the CATCH trial; ISRCTN34884569).

Methods

BSI rates using standard CVCs were estimated through linkage of national PICU audit data (PICANet) with laboratory surveillance data. We estimated the number of BSI averted if PICUs switched from standard to antibiotic-impregnated CVCs by applying the CATCH trial rate-ratio (0.40; 95% CI 0.17,0.97) to the BSI rate using standard CVCs. The value of healthcare resources made available by averting one BSI as estimated from the trial economic analysis was £10,975; 95% CI -£2,801,£24,751.

Results

The BSI rate using standard CVCs was 4.58 (95% CI 4.42,4.74) per 1000 CVC-days in 2012. Applying the rate-ratio gave 232 BSI averted using antibiotic CVCs. The additional cost of purchasing antibiotic-impregnated compared with standard CVCs was £36 for each child, corresponding to additional costs of £317,916 for an estimated 8831 CVCs required in PICUs in 2012. Based on 2012 BSI rates, management of BSI in PICUs cost £2.5 million annually (95% uncertainty interval: -£160,986, £5,603,005). The additional cost of antibiotic CVCs would be less than the value of resources associated with managing BSI in PICUs with standard BSI rates >1.2 per 1000 CVC-days.

Conclusions

The cost of introducing antibiotic-impregnated CVCs is less than the cost associated with managing BSIs occurring with standard CVCs. The long-term benefits of preventing BSI could mean that antibiotic CVCs are cost-effective even in PICUs with extremely low BSI rates.     

Communication about Children's Clinical Trials as Observed and Experienced: Qualitative Study of Parents and Practitioners

Background

Recruiting children to clinical trials is perceived to be challenging. To identify ways to optimise recruitment and its conduct, we compared how parents and practitioners described their experiences of recruitment to clinical trials.

Methods and Findings

This qualitative study ran alongside four children''s clinical trials in 11 UK research sites. It compared analyses of semi-structured interviews with analyses of audio-recordings of practitioner-family dialogue during trial recruitment discussions. Parents from 59 families were interviewed; 41 had participated in audio-recorded recruitment discussions. 31 practitioners were interviewed. Parents said little in the recruitment discussions contributing a median 16% of the total dialogue and asking a median of one question. Despite this, parents reported a positive experience of the trial approach describing a sense of comfort and safety. Even if they declined or if the discussion took place at a difficult time, parents understood the need to approach them and spoke of the value of research. Some parents viewed participation as an ‘exciting’ opportunity. By contrast, practitioners often worried that approaching families about research burdened families. Some practitioners implied that recruiting to clinical trials was something which they found aversive. Many were also concerned about the amount of information they had to provide and believed this overwhelmed families. Whilst some practitioners thought the trial information leaflets were of little use to families, parents reported that they used and valued the leaflets. However, both parties agreed that the leaflets were too long and wanted them to be more reader-friendly.

Conclusions

Parents were more positive about being approached to enter their child into a clinical trial than practitioners anticipated. The concerns of some practitioners, that parents would be overburdened, were unfounded. Educating practitioners about how families perceive clinical trials and providing them with ‘moral’ support in approaching families may benefit paediatric research and, ultimately, patients.     

Parents’ Agendas in Paediatric Clinical Trial Recruitment Are Different from Researchers’ and Often Remain Unvoiced: A Qualitative Study

Ensuring parents make an informed decision about their child’s participation in a clinical trial is a challenge for practitioners as a parent’s comprehension of a trial may differ from that intended by the practitioners responsible for recruitment. We explored what issues parents consider important when making a decision about participation in a paediatric clinical trial and their comprehension of these issues to inform future recruitment practice. This qualitative interview and observational study examined recruitment in four placebo-controlled, double-blind randomised clinical trials of medicines for children. Audio-recorded trial recruitment discussions between practitioners and parents (N = 41) were matched with semi-structured interviews with parents (N = 41). When making a decision about trial entry parents considered clinical benefit, child safety, practicalities of participation, research for the common good, access to medication and randomisation. Within these prioritised issues parents had specific misunderstandings, which had the potential to influence their decisions. While parents had many questions and concerns about trial participation which influenced their decision-making, they rarely voiced these during discussions about the trials with practitioners. Those involved in the recruitment of children to clinical trials need to be aware of parents’ priorities and the sorts of misunderstandings that can arise with parents. Providing trial information that is tailored to what parents consider important in making a decision about a clinical trial may improve recruitment practice and ultimately benefit evidence-based paediatric medicine.     

‘The Words Will Pass with the Blowing Wind’: Staff and Parent Views of the Deferred Consent Process,with Prior Assent,Used in an Emergency Fluids Trial in Two African Hospitals

Objective

To document and explore the views and experiences of key stakeholders regarding the consent procedures of an emergency research clinical trial examining immediate fluid resuscitation strategies, and to discuss the implications for similar trials in future.

Methods

A social science sub-study of the FEAST (Fluid Expansion As Supportive Therapy) trial. Interviews were held with trial team members (n = 30), health workers (n = 15) and parents (n = 51) from two purposively selected hospitals in Soroti, Uganda, and Kilifi, Kenya.

Findings

Overall, deferred consent with prior assent was seen by staff and parents as having the potential to protect the interests of both patients and researchers, and to avoid delays in starting treatment. An important challenge is that the validity of verbal assent is undermined when inadequate initial information is poorly understood. This concern needs to be balanced against the possibility that full prior consent on admission potentially causes harm through introducing delays. Full prior consent also potentially imposes worries on parents that clinicians are uncertain about how to proceed and that clinicians want to absolve themselves of any responsibility for the child’s outcome (some parents’ interpretation of the need for signed consent). Voluntariness is clearly compromised for both verbal assent and full prior consent in a context of such vulnerability and stress. Further challenges in obtaining verbal assent were: what to do in the absence of the household decision-maker (often the father); and how medical staff handle parents not giving a clear agreement or refusal.

Conclusion

While the challenges identified are faced in all research in low-income settings, they are magnified for emergency trials by the urgency of decision making and treatment needs. Consent options will need to be tailored to particular studies and settings, and might best be informed by consultation with staff members and community representatives using a deliberative approach.     

Participant informed consent in cluster randomized trials: review

Background

The Nuremberg code defines the general ethical framework of medical research with participant consent as its cornerstone. In cluster randomized trials (CRT), obtaining participant informed consent raises logistic and methodologic concerns. First, with randomization of large clusters such as geographical areas, obtaining individual informed consent may be impossible. Second, participants in randomized clusters cannot avoid certain interventions, which implies that participant informed consent refers only to data collection, not administration of an intervention. Third, complete participant information may be a source of selection bias, which then raises methodological concerns. We assessed whether participant informed consent was required in such trials, which type of consent was required, and whether the trial was at risk of selection bias because of the very nature of participant information.

Methods and Findings

We systematically reviewed all reports of CRT published in MEDLINE in 2008 and surveyed corresponding authors regarding the nature of the informed consent and the process of participant inclusion. We identified 173 reports and obtained an answer from 113 authors (65.3%). In total, 23.7% of the reports lacked information on ethics committee approval or participant consent, 53.1% of authors declared that participant consent was for data collection only and 58.5% that the group allocation was not specified for participants. The process of recruitment (chronology of participant recruitment with regard to cluster randomization) was rarely reported, and we estimated that only 56.6% of the trials were free of potential selection bias.

Conclusions

For CRTs, the reporting of ethics committee approval and participant informed consent is less than optimal. Reports should describe whether participants consented for administration of an intervention and/or data collection. Finally, the process of participant recruitment should be fully described (namely, whether participants were informed of the allocation group before being recruited) for a better appraisal of the risk of selection bias.     

Negotiating decisions during informed consent for pediatric Phase I oncology trials

During informed consent conferences (ICCs) for Phase I trials, oncologists must present complex information while addressing concerns. Research on communication that evolves during ICCs remains largely unexplored. We examined communication during ICCs for pediatric Phase I cancer trials using a stratified random sample from six pediatric cancer centers. A grounded theory approach identified key communication steps and factors influencing the negotiation of decisions for trial participation. Analysis suggests that during ICCs, families, patients, and clinicians exercise choice and control by negotiating micro-decisions in two broad domains: drug logic and logistics, and administration/scheduling. Micro-decisions unfold in a four-step communication process: (1) introduction of an issue; (2) response; (3) negotiation of the issue; and (4) resolution and decision. Negotiation over smaller micro-decisions is prominent in ICCs and merits further study.     

The Role of Systematic Reviews in Pharmacovigilance Planning and Clinical Trials Authorisation Application: Example from the SLEEPS Trial

Background

Adequate sedation is crucial to the management of children requiring assisted ventilation on Paediatric Intensive Care Units (PICU). The evidence-base of randomised controlled trials (RCTs) in this area is small and a trial was planned to compare midazolam and clonidine, two sedatives widely used within PICUs neither of which being licensed for that use. The application to obtain a Clinical Trials Authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) required a dossier summarising the safety profiles of each drug and the pharmacovigilance plan for the trial needed to be determined by this information. A systematic review was undertaken to identify reports relating to the safety of each drug.

Methodology/Principal Findings

The Summary of Product Characteristics (SmPC) were obtained for each sedative. The MHRA were requested to provide reports relating to the use of each drug as a sedative in children under the age of 16. Medline was searched to identify RCTs, controlled clinical trials, observational studies, case reports and series. 288 abstracts were identified for midazolam and 16 for clonidine with full texts obtained for 80 and 6 articles respectively. Thirty-three studies provided data for midazolam and two for clonidine. The majority of data has come from observational studies and case reports. The MHRA provided details of 10 and 3 reports of suspected adverse drug reactions.

Conclusions/Significance

No adverse reactions were identified in addition to those specified within the SmPC for the licensed use of the drugs. Based on this information and the wide spread use of both sedatives in routine practice the pharmacovigilance plan was restricted to adverse reactions. The Clinical Trials Authorisation was granted based on the data presented in the SmPC and the pharmacovigilance plan within the clinical trial protocol restricting collection and reporting to adverse reactions.     

Receptivity to sexual invitations from strangers of the opposite gender

This study investigated the primary conclusion from Clark and Hatfield's often cited field experiment “Consent to Sex with a Stranger” that men agree to sexual invitations from moderately attractive strangers of the opposite gender more readily than women do. In addition, this study investigated whether rates of consent are influenced by a subject's age, relationship status, rating of confederate attractiveness, and type of sexual invitation. A number of moderately attractive confederates of the opposite gender individually approached 173 men and 216 women. After a standard introduction, the confederates asked each participant one of the following three questions: “Would you go on a date with me tonight or during the week/weekend?”, “Would you come to my place tonight or during the week/weekend?”, or “Would you go to bed with me tonight or during the week/weekend?” Significantly more men than women consented to a sexual invitation. Specifically, significantly more men than women consented to the “come to my place” and “go to bed with me” conditions. For female subjects, higher ratings of confederate attractiveness were found to significantly increase the odds of consenting to a sexual invitation, whereas for men, confederate attractiveness was found not to significantly influence consent rates. Finally, relationship status was found to be a significant and strong moderating variable of consent for both men and women. Thus, men and women who are not in a relationship are significantly more likely to agree to a sexual invitation than those who are in a relationship.     

Nonregistration,discontinuation, and nonpublication of randomized trials: A repeated metaresearch analysis

BackgroundWe previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs.Methods and findingsWe included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study. Pilot, feasibility, and phase 1 studies were excluded. We extracted trial characteristics from each study protocol and systematically searched for corresponding trial registration (if not reported in the protocol) and full text publications until February 2022. For trial registrations, we searched the (i) World Health Organization: International Clinical Trial Registry Platform (ICTRP); (ii) US National Library of Medicine (ClinicalTrials.gov); (iii) European Union Drug Regulating Authorities Clinical Trials Database (EUCTR); (iv) ISRCTN registry; and (v) Google. For full text publications, we searched PubMed, Google Scholar, and Scopus. We recorded whether RCTs were registered, discontinued (including reason for discontinuation), and published. The reporting quality of RCT protocols was assessed with the 33-item SPIRIT checklist. We used multivariable logistic regression to examine the association between the independent variables protocol reporting quality, planned sample size, type of control (placebo versus other), reporting of any recruitment projection, single-center versus multicenter trials, and industry versus investigator sponsoring, with the 2 dependent variables: (1) publication of RCT results; and (2) trial discontinuation due to poor recruitment.Of the 326 included trials, 19 (6%) were unregistered. Ninety-eight trials (30%) were discontinued prematurely, most often due to poor recruitment (37%; 36/98). One in 5 trials (21%; 70/326) remained unpublished at 10 years follow-up, and 21% of unpublished trials (15/70) were unregistered. Twenty-three of 147 investigator-sponsored trials (16%) reported their results in a trial registry in contrast to 150 of 179 industry-sponsored trials (84%).The median proportion of reported SPIRIT items in included RCT protocols was 69% (interquartile range 61% to 77%). We found no variables associated with trial discontinuation; however, lower reporting quality of trial protocols was associated with nonpublication (odds ratio, 0.71 for each 10% increment in the proportion of SPIRIT items met; 95% confidence interval, 0.55 to 0.92; p = 0.009). Study limitations include that the moderate sample size may have limited the ability of our regression models to identify significant associations.ConclusionsWe have observed that rates of premature trial discontinuation have not changed in the past decade. Nonpublication of RCTs has declined but remains common; 21% of unpublished trials could not be identified in registries. Only 16% of investigator-sponsored trials reported results in a trial registry. Higher reporting quality of RCT protocols was associated with publication of results. Further efforts from all stakeholders are needed to improve efficiency and transparency of clinical research.

Benjamin Speich and colleagues investigate whether rates of trial completion and publication have increased over the past decade, the extent to which non-published trials can be identified in registries, and the association between reporting quality of protocols and premature discontinuation or non-publication of trials.     

The ethical issues regarding consent to clinical trials with pre-term or sick neonates: a systematic review (framework synthesis) of the analytical (theoretical/philosophical) research

BackgroundConducting clinical trials with pre-term or sick infants is important if care for this population is to be underpinned by sound evidence. Yet, approaching the parents of these infants at such a difficult time raises challenges to obtaining valid informed consent for such research. In this study, we asked, What light does the analytical literature cast on an ethically defensible approach to obtaining informed consent in perinatal clinical trials?MethodsIn a systematic search, we identified 30 studies. We began our analysis by applying philosophical frameworks, which were then refined as concepts emerged from the analytical studies, to present a coherent picture of a broad literature.ResultsBetween them, the studies addressed four themes. The first three were the ethical basis for parental informed consent for neonatal and/or perinatal research, the validity of parental consent in this context, and the range of possible options in methods for gaining consent. The last was the issue of risk and the possibility of a double-standard or asymmetry in the current approaches to the requirement for consent for research and consent for clinical treatment.ConclusionsIn addressing these issues, the analysed studies showed that, whilst there are a variety of possible defences for seeking parental ‘consent’ to neonatal and/or perinatal clinical trials, these are all consistent with the strongly and widely held view that it is important that parents do give (or decline) consent for such research. So far as the method of obtaining consent is concerned, none of the existing consent processes reviewed by the research is satisfactory, and there are philosophical reasons for supposing that at least some parents will fail to give valid consent in a neonatal context. Furthermore, in giving parental ‘consent’ in a perinatal context, parents are authorising infant participation, not giving ‘proxy consent’. Finally, there are reasons for giving weight to both parental ‘consent’ and the infant’s best interests in both research and clinical treatment. However, there are also reasons to treat these factors differently in the two contexts, and this may be partly due to the differing relevance of risk in each case. A significant gap is the lack of any detailed discussion of a process of emergency and/or urgent ‘assent’, in which parents assent or refuse their baby’s participation as best they can during the emergency and later give full consent to continuing participation and follow-up.

Electronic supplementary material

The online version of this article (doi:10.1186/s13063-016-1562-3) contains supplementary material, which is available to authorized users.     

Improving Survey Response Rates from Parents in School-Based Research Using a Multi-Level Approach

BackgroundWhile schools can provide a comprehensive sampling frame for community-based studies of children and their families, recruitment is challenging. Multi-level approaches which engage multiple school stakeholders have been recommended but few studies have documented their effects. This paper compares the impact of a standard versus enhanced engagement approach on multiple indicators of recruitment: parent response rates, response times, reminders required and sample characteristics.MethodsParents and teachers were distributed a brief screening questionnaire as a first step for recruitment to a longitudinal study, with two cohorts recruited in consecutive years (cohort 1 2011, cohort 2 2012). For cohort 2, additional engagement strategies included the use of pre-notification postcards, improved study materials, and recruitment progress graphs provided to school staff. Chi-square and t-tests were used to examine cohort differences.ResultsCompared to cohort 1, a higher proportion of cohort 2 parents responded to the survey (76% versus 69%; p < 0.001), consented to participate (71% versus 56%; p < 0.001), agreed to teacher participation (90% versus 82%; p < 0.001) and agreed to follow-up contact (91% versus 80%; p < 0.001). Fewer cohort 2 parents required reminders (52% versus 63%; p < 0.001), and cohort 2 parents responded more promptly than cohort 1 parents (mean difference: 19.4 days, 95% CI: 18.0 to 20.9, p < 0.001).ConclusionThese results illustrate the value of investing in a relatively simple multi-level strategy to maximise parent response rates, and potentially reduce recruitment time and costs.     

Task shifting and integration of HIV care into primary care in South Africa: The development and content of the streamlining tasks and roles to expand treatment and care for HIV (STRETCH) intervention

Background

The Veterans Health Administration (VHA) oversees the largest integrated healthcare system in the United States. The feasibility of a large-scale, nationwide, group-randomized implementation trial of VHA outpatient practices has not been reported. We describe the recruitment and enrollment of such a trial testing a clinician-directed, Internet-delivered intervention for improving the care of postmyocardial infarction patients with multiple comorbidities.

Methods

With a recruitment goal of 200 eligible community-based outpatient clinics, parent VHA facilities (medical centers) were recruited because they oversee their affiliated clinics and the research conducted there. Eligible facilities had at least four VHA-owned and -operated primary care clinics, an affiliated Institutional Review Board (IRB), and no ongoing, potentially overlapping, quality-improvement study. Between December 2003 and December 2005, in two consecutive phases, we used initial and then intensified recruitment strategies.

Results

Overall, 48 of 66 (73%) eligible facilities were recruited. Of the 219 clinics and 957 clinicians associated with the 48 facilities, 168 (78%) clinics and 401 (42%) clinicians participated. The median time from initial facility contact to clinic enrollment was 222 days, which decreased by over one-third from the first to the second recruitment phase (medians: 323 and 195 days, respectively; p < .001), when more structured recruitment with physician recruiters was implemented and a dedicated IRB manager was added to the coordinating center staff.

Conclusions

Large group-randomized trials benefit from having dedicated physician investigators and IRB personnel involved in recruitment. A large-scale, nationally representative, group-randomized trial of community-based clinics is feasible within the VHA or a similar national healthcare system.     

Self-help materials for the prevention of smoking relapse: study protocol for a randomized controlled trial

Background

In clinical trials in childhood asthma, outcomes reflecting short-term disease activity are frequently measured, whilst functional status, quality of life (QoL), and long-term treatment effects are rarely assessed. There is also non-uniformity across studies in the selection and measurement of outcomes within these domains. The development of a core outcome set has the potential to reduce heterogeneity between trials, lead to research that is more likely to have measured relevant outcomes, and enhance the value of evidence synthesis by reducing the risk of outcome reporting bias and ensuring that all trials contribute usable information.

Methods

Paediatricians and specialist nurses, identified through the British Paediatric Respiratory Society, completed a two-round Delphi survey. Separate cohorts of parents of children younger than 18?years, recruited in clinics, participated in each round. Young people with asthma, aged at least 13?years, participated in the first round. Outcomes were identified separately for preschool and school-aged children. We identified outcomes considered important in routine clinical assessment by clinicians and parents/young people. In round 1, 46 clinicians suggested outcomes they considered important when deciding whether to adjust a child??s asthma therapy regime, and 49 parents/young people were asked, using open questions, how they judged whether their child??s (for young people, their own) asthma therapy was appropriate. Two researchers independently classified responses into appropriate, corresponding outcomes. In round 2, 43 clinicians and 50 parents scored, from 0?C4, the importance of each outcome suggested by at least 10?% of round 1 responders and selected the three most important.

Results

The most important outcomes, when making shared decisions about regular therapies for school-aged and preschool children with asthma, were daytime and nocturnal symptoms, exacerbations, QoL, and mortality. Results from parents and clinicians were generally concordant, but parents placed more emphasis on long-term treatment effects.

Conclusions

We have developed a methodology to identify outcomes of most relevance to clinicians, parents, and young people when evaluating regularly administered therapies for asthma. Daytime and nocturnal symptoms, exacerbations, QoL, and mortality are particularly important outcomes that should be measured and reported in all clinical trials of regular therapies for children with asthma.     

Strategies for increasing recruitment to randomised controlled trials: systematic review

Background

Recruitment of participants into randomised controlled trials (RCTs) is critical for successful trial conduct. Although there have been two previous systematic reviews on related topics, the results (which identified specific interventions) were inconclusive and not generalizable. The aim of our study was to evaluate the relative effectiveness of recruitment strategies for participation in RCTs.

Methods and Findings

A systematic review, using the PRISMA guideline for reporting of systematic reviews, that compared methods of recruiting individual study participants into an actual or mock RCT were included. We searched MEDLINE, Embase, The Cochrane Library, and reference lists of relevant studies. From over 16,000 titles or abstracts reviewed, 396 papers were retrieved and 37 studies were included, in which 18,812 of at least 59,354 people approached agreed to participate in a clinical RCT. Recruitment strategies were broadly divided into four groups: novel trial designs (eight studies), recruiter differences (eight studies), incentives (two studies), and provision of trial information (19 studies). Strategies that increased people''s awareness of the health problem being studied (e.g., an interactive computer program [relative risk (RR) 1.48, 95% confidence interval (CI) 1.00–2.18], attendance at an education session [RR 1.14, 95% CI 1.01–1.28], addition of a health questionnaire [RR 1.37, 95% CI 1.14–1.66]), or a video about the health condition (RR 1.75, 95% CI 1.11–2.74), and also monetary incentives (RR1.39, 95% CI 1.13–1.64 to RR 1.53, 95% CI 1.28–1.84) improved recruitment. Increasing patients'' understanding of the trial process, recruiter differences, and various methods of randomisation and consent design did not show a difference in recruitment. Consent rates were also higher for nonblinded trial design, but differential loss to follow up between groups may jeopardise the study findings. The study''s main limitation was the necessity of modifying the search strategy with subsequent search updates because of changes in MEDLINE definitions. The abstracts of previous versions of this systematic review were published in 2002 and 2007.

Conclusion

Recruitment strategies that focus on increasing potential participants'' awareness of the health problem being studied, its potential impact on their health, and their engagement in the learning process appeared to increase recruitment to clinical studies. Further trials of recruitment strategies that target engaging participants to increase their awareness of the health problems being studied and the potential impact on their health may confirm this hypothesis. Please see later in the article for the Editors'' Summary     

Could the Decision of Trial Participation Precede the Informed Consent Process? Evidence From Burkina Faso

Background

Over the last years, the number of clinical trials carried out in low-income countries with poor medical infrastructure and limited access to health care has increased. In these settings, the decision of participating in a clinical study may be influenced by factors related to participants’ vulnerability that limit the efficacy of the informed consent.

Methods

A mixed methods social science study, based on the triangulation of qualitative and quantitative data, was carried out in a socio-economically disadvantaged and semi-urban area of Bobo Dioulasso, Burkina Faso. The study aimed at assessing the relevance of the informed consent procedure on the decision-making process of the parents and/or guardians of potential participants in a pediatric malaria trial.

Results

For most parents (70.4%), the decision of participating had already been taken before undergoing the informed consent process and was based on the information conveyed through the community. Access to free and good quality health care often inspired this decision. In addition, the parents’ willingness to have their child included in the trial made them develop active strategies to achieve this purpose.

Discussion

In a context of socio-economic vulnerability and poor access to free health care, the process of informed consent does not always accomplish its goal of informing people and enabling them to make a free and informed decision. This information role is somehow anticipated by the community and trial participation becomes a strategic action to secure otherwise unavailable health resources leading community members to decide on participation even prior to the informed consent process.     

Recruitment of underage test persons: motivators and barriers in an anthropological EU-survey on a sensitive topic

Recruiting test persons is crucial in many scientific fields. The recognition of motivators or barriers to survey participation may support the design and recruitment strategy of future studies. The recruitment of under age test persons is very complex and sensitive. This paperpresents and analyses the experiences in recruitment of female juveniles (10-18 years old) in Germany, Italy and Lithuania within the context of an EU funded project concerning the extremely sensitive topic of "child pornography". The purpose of the project was to develop a method for age estimation of juveniles on photographs and videos. The faces of the test persons were photographed and anthropologically measured after an informed consent was signed by their parents and themselves. The analysis of the recruitment strategies and response rates revealed that culturally influenced factors played a significant role in the individual decision for or against a participation in the study. In all countries, the sensitive topic of child pornography had a great influence on the decision process. Many German parents agreed especially in light of this topic while in Italy and Lithuania the word "child pornography" triggered a very negative response. In Germany, the anthropological investigation of the faces provoked negative associations with the anthropometric surveys in the Third Reich. Social and political climate were further relevant factors for decision-making especially in Lithuania. The "top-down" principle of recruitment proved to be very effective for this kind of study. The authorities of headmasters, scientists and institutions positively influenced the decisions of the parents.     

Bias in survival estimates created by a requirement for consent to enter a clinical breast cancer registry

BackgroundA requirement for consent for inclusion may bias the results from a clinical registry. This study gives a direct measure of this bias, based on a population-based clinical breast cancer registry where the requirement for consent was removed after further ethical review and data could be re-analysed.MethodsIn Auckland, New Zealand, the population-based clinical breast cancer registry required written patient consent for inclusion from 2000-2012. A subsequent ethical review removed this requirement and allowed an analysis of consented and non-consented patients. Kaplan-Meier survival to 10 years (mean follow-up 5.1 years, maximum 13.9 years), demographic and clinical characteristics were compared. Of 9244 women with invasive cancer, 926 (10.4%) were not consented, and of 1642 women with ductal carcinoma in situ, 245 (14.9%) were not consented.ResultsSurvival was much higher for consenting patients; invasive cancer, 5 year survival 83.2% (95% confidence limits 82.2–84.1%) for consenting patients, 57.1% (53.0–60.9%) for non-consenting, and 80.8% in all patients. Analyses based only on consenting patients overestimate survival in all patients by around 2% at 2, 5, and 10 years. Non-consented patients were older, more often of Pacific ethnicity, had fewer screen-detected cancers, and more often had metastatic disease; they less frequently had primary surgery or systemic treatments.ConclusionData from a registry requiring active consent gives an upward bias in survival results, as non-consenting patients have more extensive disease, less treatment, and lower survival. To give unbiased results active consent should be not required in a clinical cancer registry.     

Reporting of informed consent, standard of care and post-trial obligations in global randomized intervention trials: a systematic survey of registered trials

Objective:  Ethical guidelines are designed to ensure benefits, protection and respect of participants in clinical research. Clinical trials must now be registered on open-access databases and provide details on ethical considerations. This systematic survey aimed to determine the extent to which recently registered clinical trials report the use of standard of care and post-trial obligations in trial registries, and whether trial characteristics vary according to setting.
Methods:  We selected global randomized trials registered on http://www.clinicaltrials.gov and http://www.controlled-trials.com . We searched for intervention trials of HIV/AIDS, malaria, and tuberculosis from 9 October 2004, the date of the most recent version of the Helsinki Declaration, to 10 April 2007.
Results:  We collected data from 312 trials. Fifty-eight percent (58%, 95% CI  =  53 to 64) of trial protocols report informed consent. Fifty-eight percent (58%, 95% CI  =  53 to 64) of trials report active controls. Almost no trials (1%, 95% CI  =  0.5 to 3) mention post-trial provisions. Most trials measure surrogate outcomes. Twenty percent (20%, 95% CI  =  16 to 25) of trials measure patient-important outcomes, such as death; and the odds that these outcomes are in a low income country are five times greater than for a developed country (odds ratio (OR) 5.03, 95% CI  =  2.70 to 9.35, p  = < 0.001). Pharmaceutical companies are involved in 28% (CI  =  23 to 33) of trials and measure surrogate outcomes more often than nonpharmaceutical companies (OR 2.45, 95% CI  =  1.18 to 5.09, p  =  0.31).
Conclusion:  We found a large discrepancy in the quality of reporting and approaches used in trials in developing settings compared to wealthier settings.     

Consent for Brain Tissue Donation after Intracerebral Haemorrhage: A Community-Based Study

Background

Spontaneous intracerebral haemorrhage is a devastating form of stroke and its incidence increases with age. Obtaining brain tissue following intracerebral haemorrhage helps to understand its cause. Given declining autopsy rates worldwide, the feasibility of establishing an autopsy-based collection and its generalisability are uncertain.

Methods

We used multiple overlapping sources of case ascertainment to identify every adult diagnosed with intracerebral haemorrhage between 1^st June 2010-31^st May 2012, whilst resident in the Lothian region of Scotland. We sought consent from patients with intracerebral haemorrhage (or their nearest relative if the patient lacked mental capacity) to conduct a research autopsy.

Results

Of 295 adults with acute intracerebral haemorrhage, 110 (37%) could not be approached to consider donation. Of 185 adults/relatives approached, 91 (49%) consented to research autopsy. There were no differences in baseline demographic variables or markers of intracerebral haemorrhage severity between consenters and non-consenters. Adults who died and became donors (n = 46) differed from the rest of the cohort (n = 249) by being older (median age 80, IQR 76–86 vs. 75, IQR 65–83, p = 0.002) and having larger haemorrhages (median volume 23ml, IQR 13–50 vs. 13ml, IQR 4–40; p = 0.002).

Conclusions

Nearly half of those approached consent to brain tissue donation after acute intracerebral haemorrhage. The characteristics of adults who gave consent were comparable to those in an entire community, although those who donate early are older and have larger haemorrhage volumes.