From initial group meetings, we seemed headed towards a Chlamydia home testing kit. After some discussions with our PIs, we decided that this was too specific, and branched it out to cover STIs in geneal. Since we had a luciferase specialist with access to thermostable luciferase as our secondary PI, Dr Amit Jathoul, we decided to focus on luciferase as our fluorescent marker for our biosensor. We then incorporated this into the basis of a CRISPR/cas9 based diagnostic kit
Initial advice on reducing false positives, and final product design
We approached Dr Patricke Hardinge for initial advice before designing our project, as he is a researcher working on a diagnostic that also uses luciferase, and depends on a light reaction, but is currently in the market (Lumora).
He emphasised two points:
- The fidelity of the reaction is vital- therefore, we should increase the specificity of our test by designing a test that requires two guide RNAs to bind, and two dcas9s to recognise a DNA sequence for a positive result.
- He also helped us consider the hardware of a final product. It must be cheap to produce but effective to show a light reaction, e.g. a photodiode.
We applied his advice on improving the fidelity of our diagnostic when designing our guide RNAs.
Biological Safety Advisor- GM regulations and 'containment use'
After being denied the ability to take out GM plates for a demonstration at Techniquest, as they are not based in a GM registered building, we decided to interview Rachel Coombe, the Biological Safety Advisor at Cardiff School of Biosciences on GM regulations related to her work. She explained GM regulations set by the HSE, and terms like 'contained use', 'safe', and 'deliberate release', as well as the involvement of the regulatory bodies, which she suggested we investigate further for more specific advice related to our project. She also specified that cell-free systems are preferred from a GM regulatory viewpoint because they are simpler to license.
Further advice from MHRA, and wider social implications
After implementing this, we decided to investigate the importance of regulations and safety in diagnostic tests by asking the MHRA some questions about their importance in regulations. We decided to further explore the importance of reducing false positives: this was done by consulting MHRA on the regulatory process and by looking deeper at the human impact of testing 'positive' for a disease by consulting a retired HIV specialist social worker. This eventually led to our investigation into self-testing kits.
Investigation into self-testing kits for STIs (with HIV as a case study)
During a casual conversation with a retired social worker about our project, she raised some concerns about home testing kits for STIs, particularly HIV. This developed into a formal interview, in which she delved into the dangers of people burying their results, spreading infections, not receiving the support they need, and the potentially unmonitored effects on suicide rates.
This discussion led me to further investigate the issues raised by home testing kits for STIs, especially HIV, for which a self testing kit was approved in the UK in April 2014. BioSure is the only company that is legally allowed to sell HIV home testing kits in the UK. I wanted to learn what the general advantages and disadavantages were, how they had been taken into account to result in such a legislation, and the general public awareness of and attitudes towards various issues raised by a self testing kit.
- We conducted a survey to get the opinion of the general public. -We consulted an ethicist, Dr Jillian Craigie, on her responses to our survey results and, more generally, self-testing kit investigation.
- We asked the MHRA some questions about the regulatory process
- We consulted employees of the Terrence Higgins Trust (THT) and National Aids Trust (NAT) on empirical data from BioSure's HIV self-testing kits, including the THT's distribution of free BioSure HIV self-testing kits.
At the Science Cafe talk, we distributed our survey to gather the opinion of the audience, the vast majority of whom thought self-testing kits should be available for everyone, and were not concerned about people burying results. At the end of the second half of the presentation, after having gathered the results in the break, we brought up the issues raised in our investigation on self-testing kits.
Resulting Report: Should Cas-Find be used as a self testing kit for STIs?
When planning a point of care STI diagnostic tool that would eventually become Cas-Find, we envisaged it as a self testing kit for use at home. Our motivations were speed, saving the NHS time and money, and convenience. However, as our focus opened up from just chlamydia to a tool adaptable for all STIs, we began to think about the ethical and wider social implications, as well as safety regulations and the economic backdrop. Although not widely considered a life changing STI, chlamydia, the most commonly diagnosed STI with 200,288 diagnoses in 2015, still comes with issues that require support, such as potential infertility, and any treatment still requires medical consultation. We consulted many experts and relevant literature, and conducted a survey in our quest to make an informed decision about the future use of Cas-Find. HIV became a focal point in our understanding of self-testing kits for STIs as HIV self testing kits were recently legalised in the UK, in 2014, following which BioSure's kit entered the market in 2015.
In June 2015, the Treasury, keeping to its adoption of austerity, announced cuts to public health spending by local government of £200 million. Since local sexual healthcare makes up 10% of local governments' budget, reduced services in diagnosis and treatment of STIs to deal with demand is predicted for the coming decades. A report by the FPA strongly implies that a 10% cut in sexual healthcare expenditure will result in greater healthcare expenditure further down the line. For example, earlier diagnosis of HIV saves the NHS great amounts of money: patients are less likely to transmit the infection to others if they are treated earlier, saving money later on, and the cost of caring for a HIV patient to the NHS is reduced by half with earlier diagnoses.
Therefore, earlier and cheaper testing that can meet higher demands seems a suitable option. This is where more widespread usage of point of contact testing for STIs comes in: shorter and fewer GP appointments, no need to send samples to a lab, and instantaneous results. Of course, the cost can be further reduced by the employment of accurate self-testing kits that appeal to consumers.
However, economic considerations alone do not justify the widespread production of self-testing kits for a range of STIs.
Wider Social Considerations
All STI diagnoses require medical and, in some cases, social support. Currently, the majority of this is provided at GPs, sexual health clinics, or through referrals to external bodies. If all STI testing kits can be mail ordered or bought over the counter, medical and social support access may come down to self-referrals and personal preference.
A conversation with Emily Engel, a retired social worker who spent 1990-2000 working with HIV affected families in a London hospital, shone light on the level of support required to accompany HIV diagnosis and treatment. She has concerns about self-testing kits supporting “secrecy and denial”, stating that those at risk need “to acknowledge a need to change behaviour, maybe even lifestyle, and taking responsibility”, something that “very few people will be able to manage without support”.
Emily has seen first-hand “many people [who] went through phases of resisting the changes they needed to make, including telling their partners, and who needed a lot of support to come to terms with this: after all, it is a life-changing diagnosis, even if it isn’t a terminal diagnosis anymore.” A core part of her job as a social worker was “helping people to see the wider implications of various courses of action and make the best decisions in the circumstances.”
She specified that the pre-test counselling that she offered meant preparing the patient for any result and its consequences: “considering their experiences and relationships and who else might need to know, [and] how a negative test might change their life as well as a positive result. It often means the person will go away and think, and maybe talk to friends and partners, to make the decision with their eyes wide open.”
This interview helped us see the need for pre-test counselling and post-test counselling, and to consider potential social behaviours that had not previously crossed our minds. With the knowledge that HIV self-testing kits exist in Britain (produced by BioSure) and the US (produced by OraQuick), we consulted the literature. Wood et al. (2014) gave a comprehensive analysis of arguments for and against the use of HIV self-testing kits, complementing Emily's concerns, while giving us new insight into the negative implications. They acknowledge that counselling and care is not linked in to testing, false negatives, and the dangers of partners coercing testing with the potential of domestic violence. This analysis links in with Emily's experiences of patients refusing to involve their partners, and her concerns about unmonitored suicide rates, particularly if the test is a false positive.
A Case Study: BioSure's HIV self-testing kits
Michael Brady's presentation to BHIVA, which was pointed out to us by a Nadia from NAT, gives interesting empirical data from HIV self-testing kits in the UK so far. The number of cases of false positives (0.02%) and failure of device to work (0.04%) are both very low. HIV self testing kits are popular with 27,917 units sold between April ‘15 and February ‘16, which our survey results also seem to suggest- see below. Although they are collecting some post-marketing surveillance data, true to Emily's concerns, there seems to be little data so far on how consumers react to certain results. Surveys on BioSure experience are optional. Feedback has been mostly positive, befitting of the economic backdrop mentioned above. However, only 4.7% of the consumers of BioSure self-testing kits from April 2015 to February 2016 provided some feedback, with only 1.96% of consumers providing solicited feedback. It is worrying that very little feedback has been provided, and that reactions are not being monitored, which is excerbated by the inability to ensure that support is provided with self-testing kits.
General Public Perceptions
We conducted a survey for the general public, which received 47 respondents. The reception to self-testing kits was mainly positive, with those saying that self-testing kits should be available to all mostly citing privacy, embarrassment of going to clinics, saving time, lifting burden on NHS, and convenience as their reasons. This seems to fit in with the 'for' arguments noted by Wood et al. (2014), for example that self-testing giving power to consumers, if they don't feel ashamed and more 'normal' testing themselves in private.
We noticed a disparity between the age of respondents, and whether they thought that kits should be available to buy: older respondents seem to be more sceptical about self-testing kits.
Another interesting relationship we noted is that it seems like people who think that pre-test counselling is not necessary for a self-testing diagnostic kit, also believe that there is no risk of people burying results.
We consulted an ethicist, Dr Jillian Craigie of Kings College London, for her input on survey comments. She particularly picked up on a comment about “Freedom of Knowledge”, saying that our survey itself does not approach a fundamental question: should people have the right to know that they have an STI, for example HIV, regardless of considerations of other issues that come with knowing in private? It is worth considering, she emphasised. Juggling a right to information and privacy with a duty of care is difficult. I think Emily provided a good account of this struggle, hinting that sometimes it is necessary for doctors to prioritise the spread of infections and how a diagnosis affects others over patient confidentiality:
“Doctors have a duty to public health, but they were reluctant to use it to breach someone’s confidentiality at the risk of losing the patient, causing a much bigger risk... sometimes I did hear them become pretty firm, telling someone if they didn't bring their partner in to the next appointment, they’d have to invite them personally!”
Personally, I think that privacy is important but that for certain matters, a utilitarian approach is beneficial where public health is concerned: intervention should trump the concept of “freedom of knowledge regardless of the consequences” if guaranteeing support to all patients testing for STIs means reducing the spread of infection and extending support to all those affected.
Conclusions and the Future: Education and Progress
We decided to think more carefully about the wider implications of a home testing kit- more consultations with experts and more data collecting is needed to make a full decision. However, we have found major areas to consider in relation to our results from this investigation. So far, we have moved away from our initial positive take on a home testing kit, and think that if we were to make one in future, we would:
- -consider not doing it for HIV- proceed cautiously!
- -consider a scheme whereby a pharmacist consultation is necessary beforehand
- consider the scale of personalised pre and post testing support available for patients
Ideally we would like to consider a solution that may deal with the elements that deter a person from getting tested for STIs at all or earlier as recorded in the surveys (e.g. embarrassment/lack of convenience/waiting time for appointments) and the greater potential of 'burying' results, not receiving the right support, passing on the infection, and unmonitored changes in suicide rates (as suggested by Emily and some survey respondents). Below are some points to consider:
This problem of embarrassment deterring people from getting tested for STIs may change with improvement in public perception towards STIs, and changes in the law to increase the rights of people with HIV: for example, the law in 2013 enabling health workers affected with HIV to perform Exposure Prone Procedures. Public perception of STIs, particularly HIV, has come a long way since the 1980s- if we build on this, perhaps 'embarrassment' will no longer be an issue. When Charlie Sheen went public with his HIV positive status, the number of people buying Biosure's HIV kit reached its highest (in the period April 2015 - February 2016); this itself suggests that increased awareness of HIV through popular culture helps to 'normalise' STI testing. The Royal Family are also promoting this, with Prince Harry recently being tested for HIV in a live stream, which resulted in 3,000 more tests being ordered. In that case, point of care testing kits in a healthcare setting would deal with the 'time saving and cost saving' issues without sacrificing the wider negative social impacts of STI testing brought about by home testing kits.
When considering a self-testing kit, one current limit is the lack of guaranteed support. Could we consider ensuring that no one can buy a test without being registered for a pre-test and post-test consultation- for example by instant messaging or a phone call? This could in theory be integrated with the activation of a self-testing kit, or connected to public social media profiles. Further research into this may prove useful.
Another aspect of “normalising” STIs is by future laws that may encourage greater widespread education in schools and in public (e.g. on social media) on STIs, the administration of such tests, the importance of support, the improvement in the legal rights of HIV positive people in professional settings, and the importance of not spreading infections. Again, we have come a long way since HIV was a taboo subject in schools, and also when any teachings related to homosexuality (including sexual health) were illegal in schools (Section 28- introduced by Thatcher but lifted in 2003 by Blair- meant that local authorities were not legally allowed to teach anything about STI prevention in relation to homosexuality). However, I think that there is still more that can be done, especially where parents can object to their children learning about STIs on religious grounds, and for that matter, teachings in religious schools where it may be assumed that young people don't engage in activities that may result in the spread of STIs.
Appendix- Quantitative Survey Data, and All Interview Transcripts
Please find quantitative survey data from 47 respondents presented below. Qualitative comments are only referred to in the report above. Statistical tests were performed on the data to evaluate potential relationships between answers to different questions, as shown in the contingency tables and box plot below- the significance of the results is referred to in the report. In addition, all the interview transcripts and consultations for our Human Practices have been compiled into a pdf below for reference.