False Positives: What are the Risks?

A false positive is a test result that incorrectly indicates that a person has a certain disease or condition.¹ Potentially stressful, expensive and even dangerous to a patient,² false positives can also skew medical data and put an extra burden on healthcare facilities.² This is why tests need to be both accurate and reliable!³

While it’s understood that false negative test results are dangerous,^4,5 we typically don’t hear as much discussion about the impact of false positive test results.² 

A false positive can occur either during a health screening or when a patient is being tested for a specific condition such as HIV, cancer or COVID.^2,6,7,8 It can have a serious impact on both patients and healthcare systems.^2,6,7,8

We know that a false negative may cause treatment to be delayed until the patient’s disease has progressed, or even become terminal.^4,5 It may also contribute to the spread of an infectious disease because the patient doesn’t take the proper precautions.⁵ 

But what about the many adverse effects a false positive result can have?^2,6,7,8

Understanding the impact of false positives on healthy infants

Newborn screening (NBS) is a prime example of just how serious and far-reaching false positive test results can be.⁶

NBS programs are designed to test newborn babies for several rare but serious diseases.^6,9 The screening is done when the baby is around 5 days old, using a few drops of blood taken from the heel,^9,10 to test for genetic, metabolic and endocrine diseases.¹⁰ 

A false positive result in NBS can have a serious physical, financial and psychological impact:

• A healthy baby will be subjected to unnecessary follow-up testing, which is often expensive and invasive.⁶ 
• Parental anxiety levels will be high.⁶ Babies with false positive results are more likely to be taken to emergency rooms or hospitalized than those with negative results.⁶ 
• A false positive for a genetic condition can affect interpersonal relationships, as families may question the baby’s paternity, or worry about which other relatives could have the same condition.¹¹
• The prevalence of false positives opens up debates in the medical space about the harm-to-benefit ratio of NBS, which is an important preventative practice.^6,12
  

False positives in testing for chronic & infectious diseases

1. Imagine thinking you have HIV (when you don't)

Being misdiagnosed with a condition as serious as HIV can have a devastating effect on a patient.¹³ If an HIV-negative person receives an incorrect HIV-positive test result, they may be faced with:

• Unnecessary antiretroviral (ARV) treatment.¹⁴
• The expenses and side effects that come with treatment.^13,14
• Social consequences like stigma and discrimination.^14,15 
• Strained community and family relationships.¹⁴ 

Patients may also not make use of interventions to help prevent HIV infection, because they think they already have it.¹⁴

In a tragic case recorded in 1993, a pregnant patient who received a positive HIV test result made the decision to terminate her pregnancy, for fear of exposing her unborn baby to the illness.¹⁵ She discovered later that her test results had been a false positive.¹⁵ 

Today, 30 years later, HIV is better understood and patients have better access to support and effective treatment,^16,17 but stigma, exclusion and emotional distress are still problems faced by HIV-positive people^16,17 – and false positive results only exacerbate these problems.¹⁴

False positives in HIV testing also impact healthcare workers and the healthcare sector as a whole: 

• Unnecessary ARV treatment means that resources like medicines and monitoring are spent on patients who don’t need them, rather than going to those who do.¹⁴ 
• When a misdiagnosis is discovered, it reduces both the credibility of test results and patients’ trust in their health services.¹⁴ 
• In some cases, when a misdiagnosis is discovered, the patient may choose to take legal action due to the distress they have experienced.¹⁵ 

2. The dreaded COVID-positive result... But is it accurate?

SARS-CoV-2 (COVID-19 or COVID) is a current example that highlights how risky a false positive test result for an infectious disease can be.² The patient may have to:

• Undergo unnecessary treatment.²
• Isolate themselves from others, missing work and losing earnings.^2,18 
• Miss or delay an important scheduled surgery.²
• Share spaces with patients who really are COVID-positive, which will expose them to the virus.²

In the healthcare sector, false positive COVID results put additional pressure on clinics and hospitals, increase wastage of resources like personal protective equipment, and distort statistics about the prevalence of the disease.^2,18

What causes false positive test results?

A false positive result and subsequent misdiagnosis can happen because of technical issues, biological issues and/or human error:^7,14,20

• Poor quality of the testing reagents. (the raw materials used in the test)²⁰
• Changes in the biological material.²⁰ 
• Damage to testing instruments or testing kits.^14,20 
• Misinterpretation of results. (e.g. in a visually-read rapid-test result)^7,20 
• High workload and stress experienced by doctors and clinic staff. (the testing providers)¹⁴ 
• Providers not following standard operating procedures.¹⁴ 
• Mislabeling, mixing up or improperly handling specimens.⁷
• Autoimmune disorders and other medical conditions affecting the patient.⁷

So how do we reduce the number of false positive results?

One thing health professionals can do is use quality testing materials.^3,20

Improved test accuracy plays a crucial role in reducing the occurrence of false positives^3,20 and that accuracy is often determined by the quality of the raw materials used to make up the test, such as its antibodies or antigens (reagents).^3,20

For tests to work properly, and to reduce the likelihood of getting an incorrect result, the materials used must have the proper sensitivity (ability to recognize clinically relevant levels of a substance) and specificity (ability to bind to a specific target).^3,20,21 

Manufacturers must also ensure consistency between batches of these materials, so that test providers get the same level of performance every time.^3,20

Medix Biochemica: Providing quality raw materials to lower the risk of false positives

Medix Biochemica is a market-leading manufacturer and supplier of in vitro diagnostics (IVD) raw materials.^22,23 Our portfolio includes high-quality antibodies, antigens, clinical chemistry enzymes, DNA polymerases, ready-to-use master mixes, and other critical raw materials for IVD testing.^22,23

Medix Biochemica practises focus on quality, consistency and reliability - all of which help to reduce the likelihood of false positives:^3,20 

• We work across multiple disciplines and disease areas and offer 5 decades of experience.^22,23
• We manufacture our products to the high quality requirements. (ISO 13485:2016, EN ISO 13485:2016 and FDA QSR)²⁴
• We follow stringent validation processes to ensure our products are suitable for their intended use.³ 
• Our core expertise is producing monoclonal and recombinant antibodies in cell culture. These processes are widely considered to be especially reliable and reproducible, with excellent batch-to-batch consistency year after year³ 

Here is a recent and compelling example of the quality and reliability Medix Biochemica provides:

We conducted a study comparing three production batches of a monoclonal antibody which binds to human chorionic gonadotropin (hCG). Each antibody batch was studied in an immunoassay setup where the sensitive detection of hCG was challenged by high concentrations of a closely related unspecific protein called Luteinizing Hormone (LH). We didn’t detect any cross-reactivity to LH on any of the three antibody batches, even at very high LH concentrations ranging up to 20,000 ng/mL. Such highly specific antibodies enable the development of very sensitive diagnostic tests with very low false positivity rates. 

Partner with Medix Biochemica for all your IVD needs – quality is at the heart of everything we do, meaning every product is meticulously qualified to ensure its consistency and reliability.²³

To discuss your needs with one of our experts, please get in touch today.

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“At 5% prevalence using summary data in symptomatic people during the first week after symptom onset, the positive predictive value (PPV) of 89% means that 1 in 10 positive results will be a false positive, and around 1 in 5 cases will be missed. 
At 0.5% prevalence using summary data for asymptomatic people, where testing was widely available and where epidemiological exposure to COVID-19 was suspected, resulting PPVs would be 38% to 52%, meaning that between 2 in 5 and 1 in 2 positive results will be false positives, and between 1 in 2 and 1 in 3 cases will be missed.”¹⁹

References:

1. False positive test result. National Cancer Institute. Accessed January 25, 2023. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/false-positive-test-result.
2. Healy B, Khan A, Metezai H, et al. The impact of false positive COVID-19 results in an area of low prevalence. Clin Med (Lond). 2021;21(1):e54-e56. doi:10.7861/clinmed.2020-0839. 
3. Expert opinion. Interview with Laura-Leena Kiiskinen, Vice President Innovation and Business Development, Medix Biochemica. November 21, 2022.
4. Petticrew M, Sowden A, Lister-Sharp D. False-negative results in screening programs. Medical, psychological, and other implications. Int J Technol Assess Health Care. 2001;17(2):164-170. doi:10.1017/s0266462300105021. 
5. Kufa T, Kharsany AB, Cawood C, et al. Misdiagnosis of HIV infection during a South African community-based survey: implications for rapid HIV testing. J Int AIDS Soc. 2017;20(Suppl 6):21753. doi:10.7448/IAS.20.7.21753. 
6. Malvagia S, Forni G, Ombrone D, et al. Development of strategies to decrease false positive results in newborn screening. Int J Neonatal Screen. 2020;6(4):84. doi:10.3390/ijns6040084. 
7. False-positive HIV test results. National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. Accessed January 25, 2023. https://www.cdc.gov/hiv/pdf/testing/cdc-hiv-factsheet-false-positive-test-results.pdf. 
8. Taksler GB, Keating NL, Rothberg MB. Implications of false-positives for future cancer screenings. Cancer. 2018;124(11):2390-2398. doi:10.1002/cncr.31271. 
9. Newborn screening overview. NHS.UK. Accessed January 25, 2023. https://www.nhs.uk/conditions/baby/newborn-screening/overview/. 
10. Newborn screening portal. Centers for Disease Control and Prevention. Accessed January 25, 2023. https://www.cdc.gov/newbornscreening/index.html. 
11. Tluczek A, Orland KM, Cavanagh L. Psychosocial consequences of false-positive newborn screens for cystic fibrosis. Qual Health Res. 2011;21(2):174-186. doi:10.1177/1049732310382919. 
12. Rosettenstein KR, Lain SJ, Wormleaton N, et al. A systematic review of the outcomes of false-positive results on newborn screening for congenital hypothyroidism. Clin Endocrinol (Oxf). 2021;95(5):766-781. doi:10.1111/cen.14562. 
13. Klarkowski D, O’Brien DP, Shanks L, et al. Causes of false-positive HIV rapid diagnostic test results. Expert Rev Anti Infect Ther. 2014;12(1):49-62. doi:10.1586/14787210.2014.866516. 
14. Johnson C, Fonner V, Sands A, et al. A report on the misdiagnosis of HIV status. Annex 14 to the Consolidated Guidelines on HIV Testing Services 2015. ISBN: 9789241508926. 
15. Coquillard N. Negligent HIV testing and false-positive plaintiffs: pardoning the traditional prerequisites for emotional distress recovery. Cleve St L Rev. 1995;43(4):655. 
16. Understanding a positive result. Centers for Disease Control and Prevention. Accessed January 31, 2023. https://www.cdc.gov/hiv/basics/hiv-testing/positive-hiv-results.html.
17. HIV and AIDS epidemic global overview. HIV.Gov. Accessed January 31, 2023. https://www.hiv.gov/federal-response/pepfar-global-aids/global-hiv-aids-overview. 
18. Braunstein GD, Schwartz L, Hymel P, et al. False positive results with SARS-CoV-2 RT-PCR tests and how to evaluate a RT-PCR-positive test for the possibility of a false positive result. J Occup Environ Med. 2021;63(3):e159-e162. doi:10.1097/JOM.0000000000002138.
19. Dinnes J, Sharma P, Berhane S, et al. Cochrane COVID-19 Diagnostic Test Accuracy Group. Rapid, point-of-care antigen tests for diagnosis of SARS-CoV-2 infection. Cochrane Database of Systematic Reviews 2022, Issue 7. doi: 10.1002/14651858.CD013705.pub3.
20. Expert opinion. Interview with Kevin Eboigbodin, PhD, MBA, Adj. Prof. Senior Director, Molecular Diagnostic Reagents at Medix Biochemica, Adj. Professor in Molecular Biology at University of Helsinki. November 17, 2022. 
21. Olliaro P, Torreele E. Managing the risks of making the wrong diagnosis: first, do no harm. Int J Infect Dis. 2021;106:382-385. doi:10.1016/j.ijid.2021.04.004.
22. What we IVDo. Medix Biochemica. Accessed January 31, 2023. https://www.medixbiochemica.com/what-we-ivdo.
23. Antibodies/antigens/enzymes. Medix Biochemica. Accessed January 31, 2023. https://www.medixbiochemica.com/antibodies-antigens-enzymes.
24. FAQs. Medix Biochemica. Accessed February 2, 2023. https://www.medixbiochemica.com/faqs. 
25. Kanto L, Svens E, Tiisala S. Comparison of eight commercial PROM tests: Actim® PROM is the only test not reporting PROM false positives for maternal sera, and not exhibiting hook effect. Medix Biochemica, Klovinpellontie 3, FI-02180 Espoo, Finland. November 2018.