Result card

  • SAF1: What are the incidence, severity and duration of direct harms to the patient related to the testing and sampling with uPA/PAI-1, Oncotype DX, or MammaPrint®?
  • SAF14: What are the incidence, severity and duration of psychological harms to the patient related to the testing and with uPA/PAI-1, Oncotype DX, or MammaPrint®? Jump to
English

What are the incidence, severity and duration of direct harms to the patient related to the testing and sampling with uPA/PAI-1, Oncotype DX, or MammaPrint®?

Authors: Iris Pasternack, Emilio Chiarolla, Narine Sahakyan, Leonor Varela

Internal reviewers: Pseudo100 Pseudo100, Pseudo163 Pseudo163, Pseudo169 Pseudo169, Pseudo219 Pseudo219, Pseudo90 Pseudo90, Pseudo94 Pseudo94

In addition to the basic search, a search was done in PubMed by IP on 15 March 2012 using search string

  • 3 (safety[Title/Abstract]) AND #2 >18 studies
  • 2 (surgical pathology[Title/Abstract]) AND #1 246
  • 1 quality[Title/Abstract] 449032

A questionnaire was sent to the manufacturers asking

  • What are the safety standards that the technology must follow?
  • What is the statistical, percentage of sampling error?
  • What systems are used to minimise or eliminate the risk of the sample contamination?

As there is no separate sampling needed for the three tests in this HTA, we did not evaluate the harms related to invasive sampling (surgery or core biopsy). Instead we looked at some general safety concerns of surgical tissue sample diagnostics, such as sample contamination, delays in transfer, incorrect labelling, and other features which may affect the reliability of the result and thus patient safety.

T = any surgical tissue analysis

I = NA

C = NA

O = errors and quality issues that affect safety

The tissue sample is cut up and prepared in the surgical theatre, moved to the further preparations gross room or the pathological laboratory, and finally sent to the manufacturer’s own laboratory or those recommended by the manufacturers for analysis. Several factors, both process dependent and operator dependent, contribute to error in this chain. The reported frequency of diagnostic errors in oncologic pathology depends on definitions and detection methods, and ranges from 1% to 15%. The large majority of diagnostic errors do not result in severe harm, although mild to moderate harm in the form of additional testing or diagnostic delays occurs in up to 50% of errors (1).

Pathology laboratories traditionally have considered two types of error: errors of accuracy and errors of precision of the test itself (2). Accuracy is the closeness of a measure to its true value, and precision is the degree to which repeated measures show the same results. But, there are additional process- and operator-dependent related errors that may affect patient safety, such as identification errors, specimen defects or contamination, and delays. In a study where surgical pathology amendment reports were analysed in a university hospital in the USA it was noticed that amendments (changes, corrections) were made to approximately five reports out of 1000. About one fifth of them were due to misidentifications (e.g. attribution of specimens to the wrong patient), one out of ten were due to specimen defects (e.g. lost or inadequate size of specimen), a quarter were due to misinterpretation (e.g. false negative), and almost half were due to reporting defects (e.g. dates, diagnostic codes) (3).

Misidentification

In summary, approximately 1/1000 patients and 2–4/1000 surgical pathology specimens end up being misidentified or having incorrect labels in the report.

Studies: Anecdotal evidence indicated that identification errors are frequent (4). Identification errors were studied in a prospective study including 136 laboratories from several countries (5). Of the 427 255 cases reviewed, 1811 had some type of mislabelling (0.4%). The entire case was mislabelled in 1.1/1000 (490) cases, 1/1000 specimens were mislabelled (796 specimens of 358 cases), 1.7/1000 blocks were mislabelled (2172 blocks in 461 cases) and  1/1000 slides were mislabelled  (2509 slides in 502 cases). Misidentification of cases and specimens occurred most often at collection or at accessioning (i.e. when specimens are received, sorted, and entered in the laboratory). In 1751 out of the 1811 mislabelled cases (97%) the mislabelling was corrected without any additional consequences. In 59 cases (3%) a correction report was issued, and in 24 cases (1%) patient care was affected some way. Another retrospective study examined quality control records for an 18-month period and identified mislabelled surgical specimens. Out of 29 500 specimens 2.5/1000 were mislabelled (6). A prospective cohort study with 21 300 surgical specimens noted that 4.3/1000 specimens were incorrectly labelled. Reasons were, in order of frequency: not labelled at all, empty container, laterality incorrect, incorrect tissue site, incorrect patient, no patient name, and no tissue site (7). The majority of routine practices for identification and labelling probably underestimate the frequency of occurrence of errors, and many errors probably go undetected (4). Errors detected before patient harm or inconvenience has occurred are often called near misses.

Contamination

Significant and worrisome levels of contamination of non-primate genome assemblies with human DNA sequences have been noted (8).

Important
Completely
Pasternack I et al. Result Card SAF1 In: Pasternack I et al. Safety In: Jefferson T, Vicari N, Raatz H [eds.]. Prognostic tests for breast cancer recurrence (uPA/PAI-1 [FEMTELLE], MammaPrint, Oncotype DX ) [Core HTA], Agenzia nationale per i servizi sanitari regionali (age.na.s), Italy ; 2013. [cited 28 November 2021]. Available from: http://corehta.info/ViewCover.aspx?id=113

What are the incidence, severity and duration of psychological harms to the patient related to the testing and with uPA/PAI-1, Oncotype DX, or MammaPrint®?

Authors: Iris Pasternack, Emilio Chiarolla, Narine Sahakyan, Leonor Varela

Internal reviewers: Pseudo100 Pseudo100, Pseudo163 Pseudo163, Pseudo169 Pseudo169, Pseudo219 Pseudo219, Pseudo90 Pseudo90, Pseudo94 Pseudo94

Information has been published on psychological harms related to prognostic genetic tests that estimate the predisposition of healthy individuals to become cancer patients. But, as the three tests in this HTA are part of the cancer management pathway, and are diagnostic aids for physicians to select the best treatment, and the time lag from testing to treatment (adjuvant chemotherapy) is short, it is less likely that these tests have similarly significant psychological consequences for patients. We looked for evidence of psychological outcomes from the effectiveness studies of this report, and identified further studies from the basic search.

In the USA, 78 women who were tested with Oncotype DX and treated for early-stage breast cancer in one clinic between 2004and 2009 were sent a questionnaire assessing their knowledge of breast cancer their experiences of testing (9). Approximately 26% (17 of 65) of women agreed or strongly agreed that getting the Oncotype DX test result made them worried and anxious. Greater endorsement of test-related distress was associated with higher actual recurrence risk based on the test, as the majority of women who experienced test related distress had intermediate or high recurrence risks based on their test results (low = 18%, 6 of 33; intermediate = 30%, 7 of 23; high = 44%, 4 of 9). Stronger feelings of distress were also related to having chemotherapy, rather than radiation, and having more frequent worries about breast cancer recurrence.

The emotions of patients receiving MammaPrint were examined in the Netherlands (10). Patients who received a concordant high-risk result from both tests, i.e. clinical and gene tests, and patients who received a discordant low-risk result in clinical tests and a high-risk result from the gene test showed significantly more negative emotions than patients who received concordant low risk results from both tests or discordant high-risk results from clinical tests and a low-risk result from the gene test.

Important
Partially
Pasternack I et al. Result Card SAF14 In: Pasternack I et al. Safety In: Jefferson T, Vicari N, Raatz H [eds.]. Prognostic tests for breast cancer recurrence (uPA/PAI-1 [FEMTELLE], MammaPrint, Oncotype DX ) [Core HTA], Agenzia nationale per i servizi sanitari regionali (age.na.s), Italy ; 2013. [cited 28 November 2021]. Available from: http://corehta.info/ViewCover.aspx?id=113