Difference between revisions of "Team:Munich/Safety"

New Regulations on IVDDs

Technological advances of the last decade facilitate development of new in vitro diagnostic devices (IVDD). Since these tests may have a high impact on individual and public health, their safety is a major concern. To keep up with scientific and technological progress and with needs of society, European Parliament adopted new regulation on in vitro diagnostic medical devices just few months ago - on 5 April 2017¹⁴. Australian Therapeutic Goods Administration issued a regulatory framework on 1 July 2010¹.

The general trend is the same - new policies are more strict and should promote safety of IVDDs. For example, while the previous directive in EU required only one out of five IVDD to be checked by a Notified Body before it was placed on the market, according to new regulation only safety class A tests (lowest risk) will be sole responsibility of the manfucaturer. All devices of higher risk classes will require involvement of Notified Body. This risk classification of IVDDs is new as well and scheme for performance evaluation during lifetime of a device was introduced. While U.S. system focuses on evidence of clinical efficiency, the FDA rarely requires clinical outcome studies¹; in contrast, new EU regulation introduces new requirements for clinical evidence including clinical data and continous performance evaluation including incident reporting.

Self-tests

Another big topic related to new IVDDs is usage of self-tests. There are several risks associated with them¹³:

Diagnostic sensitivity

False-negatives (device shows negative result, though the true result should be positive). Since self-testers often perform tests for reassurance, without considering the disadvantages¹², in the best case self-tests for high severity conditions should be available only false-negative ratio is in the similar range as for clinical tests. Poorly informed patient may be harmed in case of false-negative; treatment will postpone and condition worsen. Consumer information should promote more informed usage for self-testing¹².

False-positives (device shows positive result, though the true result should be negative). Though this fault may seem to be less harmful, since in case of testing for severe disease like HIV most of patients are aware that positive result must be confirmed³, in case of testing for milder conditions, patient may receive unnecessary and potentially harmful treatment.

Analytical sensitivity

False-negative between infection and seroconversion: this risk is related rather to immunoassays and is less relevant for tests like our which is based on detection of nucleic acids.

Accuracy

Deciding for accuracy are the performance of the test and ability of inexperienced person to properly use it¹³. While the performance is a subject of regulation, it was shown that some devices fail to deliver clear complete usage instructions¹³. But even provided instructions are not always followed by all the users¹³. There are contradictiory results provided regarding this aspect, for example a review of studies on usage of HIV self-tests showed that most participants properly performed home tests and obtained accurate results³. The same review suggests people often had trouble performing blood-based tests. On the other hand result of a study among young adults suggests that many of them did not follow all instructions while performing the test for such severe condition as HIV infection⁴.

A poorly functioning home HIV test may thereby undermine confidence in the reliability of HIV testing more generally and weaken critical efforts to expand HIV detection and linkage to lifesaving care for the estimated 300 000 U.S. citizens with unidentified HIV infection².

Absence of professional counseling

In case of self-test user does not get immediate counseling from health professional, which may cause possible delayed entry to care¹¹. Currently available HIV self-tests have limited follow-up options, for example, in U.S. they mostly provide only phone number that participant may call⁸. Rather governmental programs of follow-up counseling are required with clear instructions of acting in case of positive test. This study also points out interesting argument, that self-tests also fails to guide users whose tests are negative to prevention services so that they can reduce their future risk for HIV infection⁸. As a possible solution self-test devices may be equipped with an Internet of Things module reporting the case with delivery of timely, active follow-up counseling and referrals over the phone⁸.

Some of users may initiate self-treatment based on results they found on Internet, which may be misleading and harmful for their health.

Wrong interpretation of results by badly informed user may cause interrupt of treatment or change of dosages of taken mediacations.

Facing positive result for severe condition

Positive result for severe disease may have an effect on emotional and psychological condition of user. Before making self-tests for many diseases available to general public, this effect must be studied more thoroughly.

Overall effect on public health

There are not many studies conducted yet since there are self-test for few specific conditions available on the market until now and effect of ability to test yourself for everything is not known. Before the introduction of self-test for HIV, mathematical model in one study prognosed increase in HIV among men having sex with men, even if home-use tests will cause overall testing⁶.

Another concern is not reaching the target group. Before first HIV ST was permitted in the U.S., some experts expected that test will be mostly used by wealthy HIV-uninfected people, so that it will not fulfill its goal to help infected people to discover their condition². Their study suggested test may have the perverse effect of false-positive and false-negative results. On the other hand, it was shown in another study that self-test usage in Netherlands was higher among high-risk individuals⁷.

Probably not all the users who were tested positive for severe condition will ask for professional medical counseling, even if it’s available. Some diseases currently must be reported to epidemiology and infectious disease control centers to enable disease monitoring and epidemy prevention. In case of unreported self-positive epidemy may be overseen. This may be sollved by IoT module (8), but limits usage of device because of higher price.

Coercion

Another concern regarding self-tests is coercion¹¹, since it allows someone to force test usage. It may be especially the case for stigmatized conditions like HIV infection.

Counterfeit

Counterfeit self-tests which are providing false results to users may have huge effect on individual and public health. Strict regulation of tests market and informing of potential users about trusted sources of tests is crucial especially in less-developed countries.

Since our project’s ultimate goal is to diagnose infectious diseases, we thoroughly addressed safety aspects of our work. Originally we had an intention to work with saliva samples, but since our lab has S1 biosafety level, we had to find another solution. So we decided to obtain RNA of non-pathogenic parts of B.subtilis, Norwalk virus and Hepatitis virus by method of in vitro transcription. Besides that we work with E.coli only.

More details about regulations, law and safety aspects of our work can be found in our Safety Form.

References

1. Favaloro EJ, Plebani M, Lippi G. Regulation of in vitro diagnostics (IVDs) for use in clinical diagnostic laboratories: towards the light or dark in clinical laboratory testing?. Clin Chem Lab Med. 2011 Aug 30;49(12):1965-73. PubMed PMID: 21875399.
2. Walensky RP, Paltiel AD. Rapid HIV testing at home: does it solve a problem or create one?. Ann Intern Med. 2006 Sep 19;145(6):459-62. PubMed PMID: 16983134.
3. Ibitoye M, Frasca T, Giguere R, Carballo-Diéguez A. Home testing past, present and future: lessons learned and implications for HIV home tests. AIDS Behav. 2014 May;18(5):933-49. PubMed PMID: 24281697; NIHMSID: NIHMS544781; PubMed Central PMCID: PMC3988264.
4. Schnall R, John RM, Carballo-Dieguez A. Do High-Risk Young Adults Use the HIV Self-Test Appropriately? Observations from a Think-Aloud Study. AIDS Behav. 2016 Apr;20(4):939-48. PubMed PMID: 26518679; NIHMSID: NIHMS734779; PubMed Central PMCID: PMC4799728.
5. Martinez O, Carballo-Diéguez A, Ibitoye M, Frasca T, Brown W, et al. Anticipated and actual reactions to receiving HIV positive results through self-testing among gay and bisexual men. AIDS Behav. 2014 Dec;18(12):2485-95. PubMed PMID: 24858480; NIHMSID: NIHMS599022; PubMed Central PMCID: PMC4229402.
6. Katz DA, Cassels SL, Stekler JD. Replacing clinic-based tests with home-use tests may increase HIV prevalence among Seattle men who have sex with men: evidence from a mathematical model. Sex Transm Dis. 2014 Jan;41(1):2-9. PubMed PMID: 24335742; NIHMSID: NIHMS549009; PubMed Central PMCID: PMC3955208.
7. Bil JP, Prins M, Stolte IG, Dijkshoorn H, Heijman T, et al. Usage of purchased self-tests for HIV and sexually transmitted infections in Amsterdam, the Netherlands: results of population-based and serial cross-sectional studies among the general population and sexual risk groups. BMJ Open. 2017 Sep 21;7(9):e016609. PubMed PMID: 28939577; PubMed Central PMCID: PMC5623511.
8. Wray T, Chan PA, Simpanen E, Operario D. eTEST: Developing a Smart Home HIV Testing Kit that Enables Active, Real-Time Follow-Up and Referral After Testing. JMIR Mhealth Uhealth. 2017 May 8;5(5):e62. PubMed PMID: 28483744; PubMed Central PMCID: PMC5440737.
9. Haddow LJ, Robinson AJ. A case of a false positive result on a home HIV test kit obtained on the internet. Sex Transm Infect. 2005 Aug;81(4):359. PubMed PMID: 16061549; PubMed Central PMCID: PMC1745018.
10. Figueroa C, Johnson C, Verster A, Baggaley R. Attitudes and Acceptability on HIV Self-testing Among Key Populations: A Literature Review. AIDS Behav. 2015 Nov;19(11):1949-65. PubMed PMID: 26054390; PubMed Central PMCID: PMC4598350.
11. Wood BR, Ballenger C, Stekler JD. Arguments for and against HIV self-testing. HIV AIDS (Auckl). 2014;6:117-26. PubMed PMID: 25114592; PubMed Central PMCID: PMC4126574.
12. Ickenroth MH, Grispen JE, Ronda G, Tacken M, Dinant GJ, et al. Motivation and experiences of self-testers regarding tests for cardiovascular risk factors. Health Expect. 2014 Feb;17(1):60-72. PubMed PMID: 22032617; PubMed Central PMCID: PMC5060707.
13. A.W. van Drongelen, C.G.J.C.A. de Vries, J.W.G.A. Pot. Assessment of files of in vitro diagnostic devices for self-testing. Report 360050017/2008. National Institute for Public Health and Environment.
14. Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devicesOfficial Journal of the European Union Volume 60 5 May 2017