Difference between revisions of "Team:Munich/Safety"

New Regulations on IVDDs

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

The current trend is to develop new stricter policies to guarantee the safety of IVDDs. Only one out of five IVDD were required by the previous EU directive to be checked by a Notified Body, before it was placed on the market. However, the new regulation states that only the safety class A tests (lowest risk) will be sole responsibility of the manufacturer, while all devices of higher risk classes will require involvement of a Notified Body¹⁴. The risk classification of IVDDs is new itself. Besides, a scheme for performance evaluation during the lifetime of a device was introduced. While the U.S. system focuses on evidence of clinical efficiency, the FDA rarely requires clinical outcome studies¹. In contrast, the new EU regulation introduces new requirements for clinical evidence including clinical data and continuous performance evaluation including incident reporting.

Self-tests

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

Diagnostic sensitivity

False-negatives occur when the device shows a negative result, eventhough 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 if the false-negative ratio is in the similar range as for clinical tests. Otherwise poorly informed patients may be harmed in case of false-negative results; treatment will be postponed and the condition will worsen. Consumer information should promote more informed usage for self-testing¹².

False-positives occur when the device shows a positive result, though the true result should be negative. Although this incorrect result might be seen as less harmful, because a positive result for a severe disease like HIV must be then confirmed ³, a patient testing positive for a milder condition might receive unnecessary and potentially harmful treatment.

Analytical sensitivity

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

Accuracy

Accuracy depends on the performance of the test and the ability of an 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. However, even when the instructions are provided, they are not always followed by all the users¹³. There are contradictory results regarding this aspect, for example a review about the 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, the results of another study among young adults suggests that many of them did not follow all instructions while performing the test for such severe conditions as a HIV infection⁴.

A poorly functioning home test may harm credibility in the reliability of rapid tests and, for example, weaken efforts to expand HIV detection².

Absence of professional counseling

In case of self-testing the user does not get immediate counseling from a health professional, which means delayed access to professional care¹¹. Currently available HIV self-tests have limited follow-up options, for example, in the U.S. generally only a phone number is provided which participants may call⁸. Instead, governmental programs of follow-up counseling with clear further instructions are required in case of a positive result. This study also points out that self-tests additionally fail to guide users, whose tests are negative, to preventive services in order to reduce the risk of future HIV infections⁸. 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 users may initiate self-treatment based on results they found on the Internet, which may be misleading and harmful for their health.

Wrong interpretation of results by badly informed users may cause treatment interruption or changes in the dosage of prescribed medications.

Facing positive results for severe conditions

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

Overall effect on public health

Not many studies have been conducted in this regard since there are few self-testing devices for specific conditions available on the market. Thus, the effect of the ability to test yourself for everything is not known. Before the introduction of self-tests for HIV, a mathematical model in one study predicted an increase in HIV among men having sex with men, even if home-use tests would increase overall testing⁶.

Another concern is not reaching the target group. Before the first HIV ST was permitted in the U.S., some experts expected that this 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 that the test may have a perverse [CHECK] effect of false-positive and false-negative results. On the other hand, it was shown in another study that self-test usage in the 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 is available. Some diseases currently must be reported to epidemiology and infectious disease control centers to enable disease monitoring and epidemic prevention. In case that an unreported self-positive epidemic is overseen, this may be solved by an IoT module⁸, but this would limit the device usage because of a 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 a 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.

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