Lesley Goldsmith

Direct-to-consumer genomic testing: systematic review of the literature on user perspectives

Genetic tests have traditionally been offered by health professionals. However, genomic tests have been available direct to the consumer for the last decade, increasingly via the Internet. The aim of this systematic review was to ascertain the evidence concerning use of direct-to-consumer genomic testing from the consumer perspective. Primary research was identified using the search terms ‘direct-to-consumer’ and ‘genomic or genetic’ in six bibliographic databases and citation searching of findings. In all, 17 papers were reviewed: 3 qualitative and 14 quantitative. Findings indicate a low level of awareness of direct-to-consumer genomic testing and, because of the hypothetical nature of many studies, little evidence from users of such tests. Although potential users appear to be interested in information about their risks of developing common diseases, concerns were expressed about privacy of genetic risk information and the reliability of genomic tests. Consumers were anxious about the nature of the results. There appeared to be a preference to access genomic tests via a health professional, or to discuss the results and obtain advice from a health professional. Authors of only two papers recruited participants who had used direct-to-consumer tests and samples from the large quantitative studies were not representative of the population. These factors limit the value of the available evidence. However, we conclude that there is public interest in direct-to-consumer genomic tests, and that this is likely to result in an increased workload for a range of health professionals. We also consider that there are educational implications for both consumers and health professionals.

Direct to consumer genetic testing: a systematic review of position statements, policies and recommendations

Skirton H, Goldsmith L, Jackson L, O’Connor A. Direct to consumer genetic testing: a systematic review of position statements, policies and recommendations.

Incidental findings in genetic research and clinical diagnostic tests: a systematic review.

Incidental findings arise when clinically relevant genetic information about a research participant or patient is identified outside the scope of the original research objective or diagnostic test being performed. These findings can relate to carrier status for a heritable condition, misattributed paternity or increased susceptibility to a medical condition. The decision whether to disclose these findings to the research subject or patient is underpinned by many ethical, moral, and potentially legal considerations. There is an urgent need for definitive guidelines for researchers and healthcare professionals. We performed a systematic review of the relevant literature concerning the disclosure of incidental findings, based on the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses recommendations, using the prescribed flowchart and checklist. At initial screening, 473 articles were retrieved. The inclusion and exclusion criteria aimed at obtaining data that were relevant and of sufficient quality were applied and a total of four relevant studies were identified, comprising 2,680 individual participants and 1,023 guidance documents. Major themes emerging from the included articles include patient autonomy, patient welfare, harmful secrets, and genetic literacy. The lack of relevant studies emphasizes the urgent need for empirical investigations into the disclosure or non‐disclosure of genetic incidental findings, and the provision of guidelines to assist healthcare professionals and researchers.

Quality in genetic counselling for presymptomatic testing — clinical guidelines for practice across the range of genetic conditions

Presymptomatic testing (PST) is the performance of a genetic test on an asymptomatic individual at risk of a condition to determine whether the person has inherited the disease-causing mutation. Although relevant guidelines exist for specific diseases, there is no overarching protocol that can be adapted to any disorder or clinical setting in which such testing is offered. The objective of this European project was to develop a set of coherent guidelines for PST (for adult-onset monogenic conditions) for use by health professionals working in a range of disciplines, countries or contexts. To ensure the guidelines were appropriate and practice based, we organised a workshop attended by an expert group of practitioners with relevant health professional backgrounds from 11 countries. Models of service for offering PST were presented, the group then discussed different aspects of testing and the standard of care required to ensure that patients were prepared to make decisions and deal with results and consequences. After the workshop, several rounds of consultation were used with a wider group of professionals to refine the guidelines. The guidelines include general principles governing the offer of testing (eg, autonomous choice of the patient), objectives of genetic counselling in this context (eg, facilitation of decision making), logistical considerations (eg, use of trained staff) and topics to be included during counselling discussion with the patient (eg, consequences of both positive and negative outcomes). We recommend the adoption of these guidelines to provide an equitable structure for those seeking PST in any country.

Offering prenatal diagnostic tests: European guidelines for clinical practice

For over four decades, it has been possible to offer prenatal diagnostic testing for fetal abnormalities. Prenatal testing is now available for a wide range of monogenic disorders as well as chromosomal abnormalities and should be provided within the ethical framework of informed consent and autonomous choice. However, there are no published guidelines for health professionals from varied disciplines who offer prenatal diagnosis (PND) in a range of possible settings including departments of maternity, obstetrics and clinical genetics. We used an Expert Group technique to develop a set of guidelines for provision of prenatal diagnostic services. Thirteen European health professionals, all experts in PND, participated in a workshop to develop the guidelines, which were then subjected to a wide consultation process. The objective of PND was defined as providing prenatal diagnostic testing services (for genetic conditions) that enable families to make informed choices consistent with their individual needs and values and which support them in dealing with the outcome of such testing. General principles, logistical considerations, clinical care and counselling topics are all described and are equally applicable to invasive and non-invasive testing. These guidelines provide a framework for ethical clinical care; however, they are flexible enough to enable practitioners to adapt them to their particular setting. Ideally, an individualised approach to each family is required to ensure autonomous choice and informed consent regarding prenatal diagnostic testing within the local ethical and legal framework.

Informed consent to healthcare interventions in people with learning disabilities – an integrative review

AIM This paper is a report of an integrative review of informed consent to healthcare interventions in people with learning disabilities. BACKGROUND Consent to treatment lies at the heart of the relationship between patient and healthcare professional. In order for people with learning disabilities to have equity of access to health care, they need to be able to give informed consent to health interventions--or be assessed as incompetent to give consent. DATA SOURCES The British Nursing Index (BNI), CINAHL, MEDLINE, Social Care Online, ERIC and ASSIA and PsycINFO databases were searched using the search terms: Consent or informed choice or capacity or consent to treat* or consent to examin* AND Learning disab* or intellectual* disab* or mental* retard* or learning difficult* or mental* handicap*. The search was limited to papers published in English from January 1990 to March 2007. REVIEW METHODS An integrative review was conducted and the data analysed thematically. RESULTS Twenty-two studies were reviewed. The main themes identified were: life experience, interaction between healthcare professionals and participants, ability to consent, and psychometric variables. A consensus seemed to emerge that capacity to consent is greater in people with higher cognitive ability and verbal skills, but that the attitudes and behaviour of healthcare professionals was also a crucial factor. CONCLUSION The findings support use of the functional approach to assessing mental capacity for the purpose of obtaining informed consent. Future research into informed consent in people with learning disabilities is needed using real life situations rather than hypothetical vignettes.

Non‐invasive prenatal testing for aneuploidy: a systematic review of Internet advertising to potential users by commercial companies and private health providers

The development of non‐invasive prenatal testing has increased accessibility of fetal testing. Companies are now advertising prenatal testing for aneuploidy via the Internet.

An easy test but a hard decision: ethical issues concerning non-invasive prenatal testing for autosomal recessive disorders

Prenatal testing based on cell-free fetal DNA in maternal serum is now possible for specific monogenic conditions, and studies have shown that the use of non-invasive testing is supported by prospective parents and health professionals. However, some ethical issues have been raised concerning informed consent and paternal rights. The objective of this study was to explore ethical aspects of the use of non-invasive prenatal diagnostic testing for autosomal recessive disorders. We used a qualitative cross-sectional design, based on Thematic Analysis, and recruited 27 individuals of reproductive age who were carriers of one of four conditions: thalassaemia, sickle cell disease, cystic fibrosis or spinal muscular atrophy. Data were collected via focus groups or interviews. Participants were aware of the potential for such tests to be viewed as routine and suggested that obtaining written consent and allowing time for consideration is needed to facilitate autonomous choice and informed consent. All participants felt that mothers should be able to request such tests, but fathers who declined carrier testing should be made aware that fetal test results may reveal their status. We suggest that a written record of consent for non-invasive prenatal diagnosis should be used as a standard to help reinforce the serious nature of the test results. Where the fathers carrier status could be revealed through fetal testing, he should be made aware of this before the results are available. Health professionals should discuss with the pregnant woman the best way to manage unsought information about the fathers carrier status to minimise family disruption.

Recruitment to Online Therapies for Depression: Pilot Cluster Randomized Controlled Trial

Background Raising awareness of online cognitive behavioral therapy (CBT) could benefit many people with depression, but we do not know how purchasing online advertising compares to placing free links from relevant local websites in increasing uptake. Objective To pilot a cluster randomized controlled trial (RCT) comparing purchase of Google AdWords with placing free website links in raising awareness of online CBT resources for depression in order to better understand research design issues. Methods We compared two online interventions with a control without intervention. The pilot RCT had 4 arms, each with 4 British postcode areas: (A) geographically targeted AdWords, (B) adverts placed on local websites by contacting website owners and requesting links be added, (C) both interventions, (D) control. Participants were directed to our research project website linking to two freely available online CBT resource sites (Moodgym and Living Life To The Full (LLTTF)) and two other depression support sites. We used data from (1) AdWords, (2) Google Analytics for our project website and for LLTTF, and (3) research project website. We compared two outcomes: (1) numbers with depression accessing the research project website, and then chose an onward link to one of the two CBT websites, and (2) numbers registering with LLTTF. We documented costs, and explored intervention and assessment methods to make general recommendations to inform researchers aiming to use similar methodologies in future studies. Results Trying to place local website links appeared much less cost effective than AdWords and although may prove useful for service delivery, was not worth pursuing in the context of the current study design. Our AdWords intervention was effective in recruiting people to the project website but our location targeting “leaked” and was not as geographically specific as claimed. The impact on online CBT was also diluted by offering participants other choices of destinations. Measuring the impact on LLTTF use was difficult as the total number using LLTTF was less than 5% of all users and record linkage across websites was impossible. Confounding activity may have resulted in some increase in registrations in the control arm. Conclusions Practitioners should consider online advertising to increase uptake of online therapy but need to check its additional value. A cluster RCT using location targeted adverts is feasible and this research design provides the best evidence of cost-effectiveness. Although our British pilot study is limited to online CBT for depression, a cluster RCT with similar design would be appropriate for other online treatments and countries and our recommendations may apply. They include ways of dealing with possible contamination (buffer zones and AdWords techniques), confounding factors (large number of clusters), advertising dose (in proportion to total number of users), record linkage (landing within target website), and length of study (4-6 months). Trial Registration clinicaltrials.gov (Registration No. NCT01469689); http://clinicaltrials.gov/ct2/show/NCT01469689 (Archived by WebCite at http://www.webcitation.org/6EtTthDOp)

Accuracy of Geographically Targeted Internet Advertisements on Google Adwords for Recruitment in a Randomized Trial

Background Google AdWords are increasingly used to recruit people into research studies and clinical services. They offer the potential to recruit from targeted control areas in cluster randomized controlled trials (RCTs), but little is known about the feasibility of accurately targeting ads by location and comparing with control areas. Objective To examine the accuracy and contamination of control areas by a location-targeted online intervention using Google AdWords in a pilot cluster RCT. Methods Based on previous use of online cognitive behavioral therapy for depression and population size, we purposively selected 16 of the 121 British postcode areas and randomized them to three intervention and one (do-nothing) control arms. Two intervention arms included use of location-targeted AdWords, and we compared these with the do-nothing control arm. We did not raise the visibility of our research website to normal Web searches. Users who clicked on the ad were directed to our project website, which collected the computer Internet protocol (IP) address, date, and time. Visitors were asked for their postcode area and to complete the Patient Health Questionnaire (depression). They were then offered links to several online depression resources. Google Analytics largely uses IP methods to estimate location, but AdWords uses additional information. We compared locations assessed by (1) Analytics, and (2) as self-identified by users. Results Ads were shown 300,523 times with 4207 click-throughs. There were few site visits except through AdWord click-throughs. Both methods of location assessment agreed there was little contamination of control areas. According to Analytics, 69.75% (2617/3752) of participants were in intervention areas, only 0% (8/3752) in control areas, but 30.04% (1127/3752) in other areas. However, according to user-stated postcodes, only 20.7% (463/2237) were in intervention areas, 1% (22/2236) in control areas, but 78.31% (1751/2236) in other areas. Both location assessments suggested most leakage from the intervention arms was to nearby postcode areas. Analytics data differed from postcodes reported by participants. Analysis of a subset of 200/2236 records over 10 days comparing IP-estimated location with stated postcode suggested that Google AdWords targeted correctly in just half the cases. Analytics agreed with our assessment that, overall, one-third were wrongly targeted by AdWords. There appeared little evidence that people who bothered to give their postcode did not answer truthfully. Conclusions Although there is likely to be substantial leakage from the targeted areas, if intervention and control areas are a sufficient distance apart, it is feasible to conduct a cluster RCT using online ads to target British postcode areas without significant contamination. Trial Registration Clinicaltrials.gov NCT01469689; http://clinicaltrials.gov/ct2/show/NCT01469689 (Archived by WebCite at http://www.webcitation.org/681iro5OU)