An assessment of nucleic acid amplification testing for active mycobacterial infection



Download 12.08 Mb.
Page6/56
Date28.05.2018
Size12.08 Mb.
#51325
1   2   3   4   5   6   7   8   9   ...   56

Comparator


Patients with the clinical signs and symptoms of active TB will receive NAAT in addition to AFB microscopy. Standard microbial testing in Australia for TB, in people with signs and symptoms of active disease, involves AFB microscopy and culture of suitable specimens. As both the intervention and comparator groups receive AFB testing, the main comparator for NAAT is culture alone.

The patient population suspected of having an NTM infection receive NAAT in addition to culture, and this may replace further testing such as additional biopsies. Therefore, the appropriate comparator in the identified population is current testing without NAAT.


The reference standard


The accuracy of NAAT at determining the presence of MTB or NTM in a specimen will be determined using culture as the reference standard. The diagnostic accuracy of NAAT in determining the presence of rifampicin-resistant MTB in a specimen will also be determined using DST as the reference standard.

It is important to note that culture is an imperfect reference standard for the diagnosis of MTB and NTM. Not all patients who are clinically diagnosed as having TB or NTM infections (on the basis of histopathology, symptoms and response to drug therapy, as well as culture) will have received a positive culture result.


Research questions


Outlined below are the clinical questions formulated according to the information provided in the protocol, which was revised and accepted by the Protocol Advisory Subcommittee (PASC) of the MSAC.

Research questions:


  • What are the safety, effectiveness, and cost-effectiveness of NAAT versus NAAT plus AFB microscopy in diagnosing TB in patients who have signs and symptoms of TB?

  • What are the safety, effectiveness, and cost-effectiveness of NAAT versus current testing in diagnosing NTM in patients suspected of having an NTM infection?

Subquestions (for a linked evidence approach):


Accuracy

  • What is the accuracy of NAAT in the diagnosis of patients with suspected MTB, compared with AFB microscopy and culture?

  • What is the accuracy of NAAT plus AFB microscopy in the diagnosis of patients with suspected MTB, compared with AFB microscopy alone?

  • What is the accuracy of in-house NAAT compared with commercial NAAT in the diagnosis of patients with suspected MTB, using culture as the reference standard?

  • What is the accuracy of NAAT in the detection of genetic mutations on the rpoB gene that are associated with rifampicin resistance?

  • What is the accuracy of NAAT in the diagnosis of NTM in patients suspected of having an NTM infection, compared with culture?

Change in management

  • Does AFB microscopy plus NAAT to determine the presence of MTB and rifampicin resistance change patient management, compared with management decisions made based on AFB microscopy alone, in patients with a high pre-test probability of active TB?

  • Does AFB microscopy plus NAAT to determine the presence of MTB and rifampicin resistance change patient management, compared with management decisions made based on AFB microscopy alone, in patients with a low-pre-test probability of TB?

  • Does NAAT plus culture change patient management, compared with culture plus other tests, in patients suspected of having an NTM infection?

Effectiveness of change in management

  • To what extent does treating patients who have rifampicin-resistant MTB infections with alternative treatments result in better health outcomes for the patient and their contacts?

  • What is the health impact of early versus delayed treatment of TB on the individual and their contacts?

  • What adverse events (AEs) are associated with inappropriate antibiotic treatment for TB?

Diagnostic assessment framework


This assessment uses the theoretical framework outlined in the MSAC Guidelines for the assessment of diagnostic technologies (MSAC 2005).

This means that evidence of the clinical effectiveness of diagnosing MTB or NTB using NAAT requires either:



  • evidence of the effectiveness of NAAT from high-quality comparative studies evaluating the use of NAAT and subsequent treatment, compared with culture plus DST and treatment (direct evidence). RCTs provide the highest quality evidence for this comparison; or, if this is not available:

  • evidence of treatment effectiveness from high-quality comparative studies evaluating the change in management for TB, linked with applicable and high-quality evidence of the accuracy of NAAT to diagnose MTB or NTM, compared with culture plus DST. This is called ‘linked evidence’.

There was limited direct evidence available that met all the inclusion criteria that assessed the safety and effectiveness of NAAT in the diagnosis of MTB or NTB infections.

Review of literature

Literature sources and search strategies


The medical literature was searched to identify relevant studies and reviews for the period between 1990 and June 2014. Searches were conducted for the databases described in Table 5. Search terms are described in Table 6 to Table 10.

Due to the large volume of evidence for the diagnostic accuracy of NAAT compared with culture, only studies published after 2005 that provided 2x2 data suitable for meta-analysis for both AFB microscopy and NAAT compared with culture, were included in the final analysis. Studies on the only commercial NAAT product (Xpert) available in Australia were published in 2006 onwards. In-house NAAT, on the other hand, was available before 2005. However, as there have been significant changes in laboratory practice over the past 10 years (Boyle & Pai 2012; Moore, Guzman & Mikhail 2005; Nybo 2012; Public Health and Ambulatory Care 2012), it seemed reasonable to limit study eligibility to publications in the previous decade.

The diagnostic accuracy of in-house NAAT performed more than 10 years ago compared with culture was reported in two SRs. Pai et al. (2004) reported that the pooled sensitivity in pleural fluid specimens was 71% (95%CI 63, 76; k=26), and Pai et al. (2003) reported that the pooled sensitivity in CSF specimens was 76% (95%CI 57, 83; k=35). These values are much lower than that reported in this assessment for non-sputum specimens (90%; 95%CI 83, 94, k=44; see Figure 15). Thus, the inclusion of only those studies published after 2005 in the final analysis provided more-accurate data on the accuracy of NAAT as currently performed in the diagnostic laboratory.

An SR by Takwoingi et al. (2013) showed that there was a > 2-fold discrepancy in the relative diagnostic odds ratio between non-comparative studies (that compared either the index test or the comparator with the reference standard) and comparative studies (that compared both the index test and the comparator with the reference standard). Thus, these studies provide the highest quality evidence available to assess the accuracy of NAAT and AFB microscopy compared with culture to diagnose MTB infections.



Table 5 Electronic databases searched

Electronic database

Period covered

Cochrane Library – including, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, the Cochrane Central Register of Controlled Trials (CENTRAL), the Health Technology Assessment Database, the NHS Economic Evaluation Database

1990 – 6/2014

Current Contents

1990 – 6/2014

Embase

1990 – 6/2014

PubMed

1990 – 6/2014

Web of Science – including Science Citation Index Expanded and Conference Proceedings Citation Index- Science

1990 – 6/2014

Cinahl

1990 – 6/2014

Econlit

1990 – 6/2014

Scopus

1990 – 6/2014

Table 6 Search terms used for NAAT for MTB (direct evidence, accuracy and change in management)

Element of clinical question

Search terms

Population

(tuberculosis OR MTB OR MTB/RIF OR “tubercle bacillus” OR Tuberculosis [MeSH] OR Mycobacterium OR “M. africanum” OR “M. bovis” OR “M. microti” OR “M. canettii” OR “M. caprae” OR “M. pinnipedii” OR “M. mungi”)

Intervention

(Amplicor OR Amplified OR “Direct Test” OR “Direct Detection” OR TaqMan OR Xpert OR “nucleic acid amplification” OR NAAT OR “polymerase chain reaction” OR PCR OR “Nucleic Acid Amplification Techniques” [MeSH])

Comparator (if applicable)

N/A

Outcomes (if applicable)

N/A

Limits

1990 – June 2014; NOT (Other Animals NOT Humans)

MeSH = Medical Subject Heading, based on a Medline/PubMed platform; N/A = not applicable

Table 7 Search terms used for NAAT for NTM (direct evidence, accuracy and change in management)



Element of clinical question

Search terms

Population

(“mycobacterium nontuberculous” OR “Mycobacterium Infections, Nontuberculous” [MeSH] OR “environmental mycobacteria” OR “mycobacteria other than tuberculosis” OR MOTT OR NTM OR NTMB OR “M. abscessus” OR “M avium” OR “M. chelonae” OR “M. flavescens” OR “M. fortuitum” OR “M. genavense” OR “M. gordonae” OR “M. haemophilum” OR “M. intracellulare” OR “M. kansasii” OR “M. malmoense” OR “M. marinum” OR “M. peregrinum” OR “M. scrofulaceum” OR “M. simiae” OR “M. smegmatis” OR “M. szulgai” OR “M. terrae” OR “M. ulcerans” OR “M. xenopi”)

Intervention

(Amplicor OR Amplified OR “Direct Test” OR “Direct Detection” OR Xpert OR TaqMan OR “nucleic acid amplification” OR NAAT OR “polymerase chain reaction” OR PCR OR “Nucleic Acid Amplification Techniques” [MeSH])

Comparator (if applicable)

N/A

Outcomes (if applicable)

N/A

Limits

1990 – June 2014; NOT (Other Animals NOT Humans)

MeSH = Medical Subject Heading, based on a Medline/PubMed platform; N/A = not applicable

Table 8 Search terms used for impact of early identification of drug resistance and alternative treatment



Element of clinical question

Search terms

Population

(tuberculosis OR MTB OR MTB/RIF OR “tubercle bacillus” OR Tuberculosis [MeSH] OR Mycobacterium OR “M. africanum” OR “M. bovis” OR “M. microti” OR “M. canettii” OR “M. caprae” OR “M. pinnipedii” OR “M. mungi”) AND (“rpoB protein, Mycobacterium tuberculosis” [Supplementary Concept] OR rpoB OR resistant OR resistance OR “multidrug resistant” OR MDR OR “Drug resistance, Bacterial” [MeSH])

Intervention

N/A

Comparator (if applicable)

(Rifampin [MeSH] OR rifampicin OR benemycin OR rimactan OR tubacin OR rifadin OR rimactane OR isoniazid)

Outcomes (if applicable)

(infectious OR contagious OR contacts OR delay OR “excess morbidity” OR “excess mortality” OR public health OR outbreak)

Limits

1990 – June 2014; NOT (Other Animals NOT Humans)

MeSH = Medical Subject Heading, based on a Medline/PubMed platform; N/A = not applicable

Table 9 Search terms used for impact of early versus delayed treatment for TB



Element of clinical question

Search terms

Population

(tuberculosis OR MTB OR MTB/RIF OR “tubercle bacillus” OR Tuberculosis [MeSH] OR Mycobacterium OR “M. africanum” OR “M. bovis” OR “M. microti” OR “M. canettii” OR “M. caprae” OR “M. pinnipedii” OR “M. mungi”)

Intervention and comparator

(early OR delayed OR delay OR immediate OR timely OR speed OR expedited) AND (antibiotics OR drug OR treatment OR isoniazid OR rifampicin OR rifampin OR ethambutol OR myambutol OR pyrazinamide)

Outcomes (if applicable)

N/A

Limits

1990 – June 2014; NOT (Other Animals NOT Humans)

MeSH = Medical Subject Heading, based on a Medline/PubMed platform; N/A = not applicable

Table 10 Search terms used for impact of inappropriate antibiotic use



Element of clinical question

Search terms

Population

(tuberculosis OR MTB OR MTB/RIF OR “tubercle bacillus” OR Tuberculosis [MeSH] OR Mycobacterium OR “M. africanum” OR “M. bovis” OR “M. microti” OR “M. canettii” OR “M. caprae” OR “M. pinnipedii” OR “M. mungi”)

Intervention

(antibiotics OR drug OR treatment OR isoniazid OR rifampicin OR rifampin OR ethambutol OR myambutol OR pyrazinamide)

Outcomes (if applicable)

(“adverse events” OR side-effects OR reaction* OR “Drug-Related Side Effects and Adverse Reactions”[MeSH])

Study type

“systematic review” OR “meta-analysis”

Limits

1990 – June 2014; NOT (Other Animals NOT Humans)

MeSH = Medical Subject Heading, based on a Medline/PubMed platform; N/A = not applicable


Download 12.08 Mb.

Share with your friends:
1   2   3   4   5   6   7   8   9   ...   56



The database is protected by copyright ©ininet.org 2024
send message
    Main page
process used
australian government department