Independent committee to evaluate KTPH lab error that led to breast cancer patients getting unnecessary treatment

• About 200 breast cancer patients were misdiagnosed with a type of malfunctioning gene due to a lab error at Khoo Teck Puat Hospital
• The National Healthcare Group has set up an independent committee to evaluate the incident, Senior Minister of State Koh Poh Koon said
• Affected patients will receive a full refund of portions of their bill arising from unnecessary treatment
• The hospital will also provide financial and clinical support, including follow-up treatment where needed

SINGAPORE — The National Healthcare Group (NHG) has set up an independent review committee to carry out a “thorough evaluation” of an incident at Khoo Teck Puat Hospital (KTPH) that led to 200 breast cancer patients being misdiagnosed with a type of malfunctioning gene in the past eight years.

About 90 of the patients may have received unnecessary treatment, the authorities revealed last month. 

On Monday (Jan 4), Dr Koh Poh Koon, who is Senior Minister of State for Health, told Parliament that affected patients will receive full refunds of the portions of their bills arising from unnecessary treatment at the hospital.

They will also receive financial and clinical support, including for ongoing and follow-up treatment that may be needed as a result of over-treatment from the misdiagnosis.

Dr Koh was responding to questions from five Members of Parliament (MPs) over the incident. 

It came about due to an incorrect process in KTPH’s laboratory in relation to tests for the human epidermal growth factor receptor 2 (HER2), a gene determining how a healthy cell grows.

Some patients were classified to be HER2-positive, instead of HER2-negative, because of slip-ups at the lab. A positive test result suggests that the gene is malfunctioning, leading to the uncontrolled growth of cells, and affects how a patient is treated, usually with a drug called Herceptin.

Initial estimates made public on Dec 11 last year showed that about 180 breast cancer patients may have to be reclassified from HER2-positive to HER2-negative, and about half of them may have received unnecessary treatment.

Dr Koh said that as of Dec 23 last year, 200 patients had been reclassified from HER2-positive to HER2 negative.

Among the parliamentary questions tabled, MP Joan Pereira of Tanjong Pagar Group Representation Constituency (GRC) wanted to know what was being done to prevent similar incidents. Dr Lim Wee Kiak, MP for Sembawang GRC, asked about the cost of medication incurred by patients who were misdiagnosed and how many of them suffered side-effects as a result of being given the wrong treatment.

In his response, Dr Koh said that the committee convened by NHG, the public healthcare cluster overseeing KTPH, comprises external experts from “multiple relevant disciplines” in the healthcare industry.

“The objective is to conduct a thorough evaluation of the incident, to understand better the lapses that have occurred and recommend appropriate measures to improve the process. This ensures that any system gaps are identified and addressed swiftly to prevent recurrence of similar incidents.”

He added that the committee’s investigations were in progress and it would provide an update when more information becomes available.

Of the 200 affected patients, 192 were treated at government hospitals and eight at private hospitals. Another eight patients have pending re-tests, Dr Koh said.

He added that KTPH and the patients’ doctors were reviewing their care plans and would assess them for potential side-effects due to the unnecessary treatment.

Common side-effects from the Herceptin treatment include diarrhoea, chills and fatigue. About 3 to 4 per cent may also experience heart problems.

On Nov 19 last year, KTPH was informed by its lab that its tests for HER2 were producing higher-than-expected rates of positive results for breast cancer patients.

Based on preliminary investigations by the lab, the inaccurate results could be due to a sub-optimal staining process.

Dr Koh said that the hospital has since stopped in-house testing of HER2 and the Ministry of Health (MOH) has not received any reports of similar risks in testing from other healthcare institutions.

KTPH has sent the samples of all patients who have tested HER2-positive since 2012 — when testing for the gene started at the hospital — to external laboratories for re-testing to determine how many had received inaccurate results. 

The department of laboratory medicine at KTPH is subject to regular inspections by MOH. This is part of regulatory processes under the Private Hospitals and Medical Clinics Act, to ensure that lab facilities, systems and processes are in place to meet safety standards for patients and employees.

The lab is also accredited by the College of American Pathologists and the last inspections by peers — done every two years — were in 2019, Dr Koh said.

Mrs Chew Kwee Tiang, KTPH’s chief executive officer, last month apologised to patients as well as their families and treating oncologists. 

“I am very sorry that they have to go through this. We will provide all the necessary support and assistance, and will do our best to take care of them,” she said, vowing to take “all the necessary steps to ensure this does not happen again”.

WHY WAS PROBLEM NOT DETECTED SOONER? 

In Parliament, Ms Cheryl Chan, MP for East Coast GRC, pressed Dr Koh on why the misdiagnoses had not been picked up earlier, despite patients going for recurring visits to their doctors. 

Dr Koh said that in any lab test, there is always the chance of a false positive or false negative happening, depending on the sensitivity and specificity of the tests. 

In the case of immunohistochemistry tests, which are used to test for HER2, a false negative or false positive could be produced if any part of the mixing process, which involves stains, dyes or counter-stains, is not done optimally.

While the false-positivity rate of the test has dropped to about 6 per cent or less over the years, “it is never going to be zero”, Dr Koh said. 

In view of this, institutions need to regularly review data accumulated over time to ensure that the false-positivity rate does not exceed 6 per cent. When that happens, a review is triggered by the multi-disciplinary tumour board that examines tumour outcomes, assessments and treatments, Dr Koh added. 

Non-Constituency MP Hazel Poa, who is from the opposition Progress Singapore Party, asked why it took such a long time to discover the errors that appeared to have started in 2012.

Dr Koh clarified that while KTPH is reviewing all its tests since 2012, this does not mean that all test results since then are erroneous. The hospital is trying to be “comprehensive and careful”, he said.

In response to Ms Poa’s question on whether a second, independent test for serious illnesses should be introduced in light of the lab error, Dr Koh said that clinicians already exercise judgement in calling for a second test should they be unsure if a particular test can predict the presence of an illness. 

When it comes to immunohistochemistry tests, patients will have to consider if a second test could delay their treatment or incur more costs, he added.

It is up to experts to draw up guidelines on the testing algorithm to decide Herceptin-related treatment, Dr Koh said.

Dr Lim of Sembawang GRC asked Dr Koh if there were avenues available for affected patients to seek compensation, citing the example of his resident who believed that she was affected but had not been contacted by the authorities. 

Dr Koh gave the assurance that patients who have not been contacted by now would not have their HER2 status affected. He emphasised again that KTPH would reach out to affected patients.