Evidence-based indications for the planning of PET or PET/CT capacities are needed
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To identify evidence-based indications for PET/PET–CT scans in support of facilities planning and to describe a pilot project in which this information was applied for an investment decision in an Austrian region. The study updates a Health Technology Assessment (HTA) report (2015) on oncological indications, extending it to neurological indications and inflammatory disorders.
A systematic literature search to identify HTA reports, evidence-based guidelines, and systematic reviews/meta-analyses (SR/MA) was performed, supplemented by a manual search for professional society recommendations and explicit “not-to-do’s”. A needs-assessment was conducted in the context of the pilot study on investing in an additional PET–CT scanner in the Austrian region of Carinthia.
Overall recommendations for indications as well as non-recommendations for the three areas (oncology, neurology, and inflammatory disorders) were compiled from the 2015 PET–HTA report and expanded for a final total of ten HTA, comprising 234 (positive and negative) recommendations from professional societies and databases, and supplemented by findings from 23 SR/MA. For the investment decision pilot study in Carinthia, 1762 PET scans were analyzed; 77.8% were assigned to the category “recommended evidence-based indications” (54.7%), “not recommended” (1.8%) or “contradictory recommendations” (21.3%). The remaining could not be assigned to any of the three categories.
The piloting of PET capacity planning using evidence-based information is a first of its kind in the published literature. On one hand, the high number of PET scans that could not be ascribed to any of the categories identified limits to the instructive power of the study to use evidence-based indication lists as the basis for a needs-assessment investment planning. On the other hand, this study reveals how there is a need to improve indication coding for enhanced capacity planning of medical services. Overall recommendations identified can serve as needs-based and evidence-based decision support for PET/PET–CT service provision.
KeywordsEvidence-based planning Needs-based planning PET/PET–CT Oncology Neurology Inflammatory disorders Advanced diagnostics
Europe is one of the largest markets for the fast-growing sector of medical devices (MDs) and diagnostic procedures, which encompass a broad and heterogeneous range of technologies. Due to the rising costs associated with introducing of new MDs and procedures into the healthcare system, payers have started to pay more attention to the effectiveness and financial implications of such new technologies. In this context, health technology assessment (HTA) has gained increasing recognition at the European level as a decision support tool .
No other medical technology has been evaluated as frequently by HTA institutions in European countries as “positron emission tomography (PET)”, or rather “positron emission tomography/computed tomography (PET/PET–CT)” [2, 3]. In its 2015 assessment report  on PET/PET–CT, the Ludwig Boltzmann Institute for Health Technology Assessment (LBI-HTA) aimed to capture the evidence base on oncological indications for a needs-based planning of PET/PET–CT facilities in Austria. It identified around 160 assessments on PET or PET–CT in a 10-year period (2004–2014), of which the first HTA were already published in 1995. This expresses uncertainty about the value of PET diagnostics in patient care. Notably, despite ongoing and controversial discussions about the patient-relevant benefits of PET/PET–CT, these technologies have rapidly been adopted both in Europe and abroad . Additionally, the majority of those assessments is not accompanied by decisions regarding the reimbursement or planning of PET/PET–CT indications or devices. However, several approaches exist to deal with (to varying degrees) uncertain evidence or contradictory recommendations around reimbursement and capacity planning in Europe and globally . In practice, capacity planning employs a mix of different methods and methodological approaches such as comparative approaches (e.g., benchmarking), analytical (e.g., health care needs-assessment) and/or reactive approaches (e.g., waiting lists). To provide volume forecasts for facility planning and workload vis-à-vis PET/PET–CT, the number of patients with (sub-)indications is important as is the estimated number of patients eligible for therapy monitoring and radiotherapy dose planning. In addition, some special features of PET/PET–CT (e.g., required radionuclides/tracers) have to be taken into account. Yet the planning of capacities based on evidence-based indications is rarely seen—neither in the literature nor in practice.
On the initiative of the German Society for Nuclear Medicine (DGN), the LBI-HTA and the Department of Health Care Management at the Berlin University of Technology collaborated to (1) update the LBI-HTA 2015 report to identify indications recommended by evidence [HTA, systematic reviews/meta-analyses (SR/MA), evidence-based guidelines (EBG)] for PET/PET–CT scans supporting facility planning in Germany and Austria and (2) describe a pilot study which applied those recommendations identified in the evidence review from step (1) to an investment decision in the Austrian region of Carinthia. The subsequent, updated, HTA report extended the scope of the 2015 report by including indications for neurology and inflammatory disorders in addition to oncological indications.
The following article summarizes both the results of the updated PET–HTA report, which has already been published (in German ), and the pilot study in Austria testing the practicalities of the recommendations.
Materials and methods
(1) Evidence-based indications and recommendations
Sources of information, search strategy, and study selection
A systematic literature search was carried out in July 2017 to identify HTA reports, SR/MA, and EBG to be included in the study. The databases MEDLINE, EMBASE, PubMed, and Cochrane Library were searched using a search strategy retrieved from a published report by the German Institute for Quality and Efficiency in Health Care (IQWiG), which was then updated and adapted . A 5-year window (2012–2017) for EBG and SR/MA was chosen . HTA for the newly included indications (neurology and inflammatory disorders) were limited to the last 10 years (2007–2017), while the most recent HTA [8, 9, 10] included in the PET–HTA report  were used for oncological indications, though oncological guidelines already included in the PET–HTA were updated if newer ones were available. Details about the searches are found in the Appendix A of the report  and a translated version is found in the Online Resource 1 of this article.
The literature was screened in a two-stage process (First: title/abstract; second: full text) by two researchers of the author group. Inclusion and exclusion criteria were determined based on the criteria from the PET–HTA report 2015  for consistency. English- and German-language HTA, SR/MA, and EBG on the benefits of PET/PET–CT were included, if they discussed (1) patient-relevant benefits; (2) diagnostic accuracy/quality or change in patient management; (3) if they focused on one of the three indications/treatment areas (oncological and neurological indications, or inflammatory diseases); (4) were developed with an evidence-based methodology (e.g., a description of a literature search referenced more than two databases, inclusion/exclusion criteria and quality assessment, and double-check principle); and (5) were freely available. Differences in the assessment of literature were resolved through discussion and consensus building. A detailed overview of the criteria for inclusion and exclusion can be found in the Online Resource 2 of this article.
In addition to the systematic search, a supplementary, comprehensive manual search for evidence-based recommendations on the use of PET/PET–CT was conducted. The selection of databases or websites [e.g., Cancer Care Ontario (CCO) and National Comprehensive Cancer Network (NCCN)] was based on the PET–HTA report 2015  and complemented by relevant sources for the two new indications. The search could not be carried out in a systematic manner due to variation in search interfaces, but the search term PET was a common factor. Up-to-date recommendations of the following national and supranational societies of nuclear medicine were included: Austrian Society of Nuclear Medicine and Molecular Imaging (ÖGN), German Society for Nuclear Medicine (DGN), Swiss Society for Nuclear Medicine (SGNM), European Association of Nuclear Medicine (EANM), Society of Nuclear Medicine and Molecular Imaging (SNMMI), and Joint Collaboration of EANM and SNMMI. Databases (e.g., Choosing Wisely, NICE Do-not-Do database) that explicitly identify “inappropriate” (not-to-do) services were also included as a source of information. Screening of documents from websites or professional societies was carried out by one person, with the extraction performed using the double-check principle. During the process of updating the HTA report, information sources were again scanned between January and February 2018.
Extraction tables were compiled separately for the three indications, using the double-check principle. In a first summary table, study characteristics were extracted separately, because they differ among HTA (e.g., reported endpoints and number of included studies), SR/MA (e.g., reference standard), and EBG (e.g., funding/sponsoring and strength of the evidence). Evidence derived from HTA and SR/MA was thus presented in the further tables including the evidence base and verbatim conclusions. The recommendations from EBG and websites and databases of national and supranational societies were first extracted in tabular form and assessed along two dimensions: (1) appropriate use criteria and (2) inappropriate use criteria (e.g., suspension of decisions, recommendations based on insufficient evidence, and disinvestment recommendations), including also the corresponding strength of the evidence. Recommendations of a certain level/strength of evidence (see Box 1) were then considered and clustered according to type and content of recommendations for further analysis into their similarities and differences.
Box 1: included professional societies and databases and the level/ strength of evidence taken into account for the recommendations
American College of Chest Physicians (ACCP): own grading system (only 1B recommendation available; grade 1B = strong recommendation, moderate quality evidence)
American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS): evidence hierarchy developed by the AANS/CNS Guidelines Committee (but no recommendation due to insufficient evidence)
American College of Radiology (ACR): ACR Appropriateness Criteria®: 7–9 = appropriate indications (4–6 = may be appropriate indications was not considered for the table, are available on request)*
British Society for Hematology (BSH): GRADE was used to evaluate LoE and to assess the strength of recommendation (only A and B recommendations were considered)
Canadian Association of Radiologists (CAR) Referral Guidelines: GRADE 1 = indicated, (“2 = Specialized Investigation” was not considered for this table, available on request)* & based on A (high-quality diagnostic studies such as studies in which a new test is independently and blindly compared with a reference standard in an appropriate spectrum of patients, etc.), B (lower case evidence in which the reference standard does not appear on all subjects, etc.), or C (studies in which the reference standard was not objective, expert opinion, etc.) were considered
Cancer Care Ontario (CCO): LoE/GoR not indicated (only literature assigned to the recommendations)
European Association of Nuclear Medicine (EANM)/Society of Nuclear Medicine and Molecular Imaging (SNMMI): only Grade A and B considered
European Federation of Neurological Societies (EFNS): good practice points not considered (lack of evidence but consensus by expert reached) and only recommendations for PET taken
German Society for Nuclear Medicine (DGN): LoE/GoR not indicated (only literature assigned to the recommendations)
International myeloma Working Group (IMWG): LoE/GoR according to OECBM (only A = Evidence of type I or consistent findings from multiple studies of types II, III, or IV and B = Evidence of II, III, or IV, findings are generally consistent) were considered
Response Assessment in Neuro-oncology working group/European Association for Neuro-Oncology (RANO/EANO): only 1–3 LoE according to OCEBM included in their study (no information of LoE for the recommendations separately)
Royal College of Radiologists and Royal College of Physicians (RCR/RCP): no LoE/GoR indicated (only literature assigned to the recommendations)
Ryken et al.: evidence hierarchy developed by the AANS/CNS Guidelines Committee (level III = Clinical uncertainty (inconclusive or conflicting evidence or opinion)
SNMMI/Alzheimer’s Association (AA): no LoE/GoR indicated (only literature assigned to the recommendations)
SNMMI + EANM and American College of Nuclear Medicine (ACNM), American College of Preventive Medicine (ACPM), American Society of Clinical Oncology (ASCO), Canadian Association of Nuclear Medicine (CANM), and Society for Pediatric Radiology (SPR): 7–9 = appropriate indications (4–6 = may be appropriate indications which were not considered for this table, available on request)
National Comprehensive Cancer Network (NCCN): only LoE category 2A was considered (= based on lower level evidence, there is uniform NCCN consensus that the intervention is appropriate; LoE 2B available on request; LoE 1 was not indicated for any of the recommendation)* & only ‘preferred’ recommendations were considered
ACR: 1–3 = not appropriate (4–6 = may be appropriate indications was not considered for the table, are available on request)*
Choosing Wisely USA (ChW) and NICE Do-not-Do database: respective recommendations (both without “ratings”) were evaluated
CAR: GRADE 5 = not indicated (GRADE 3 = not indicated initially, 4 = indicated only in specific circumstances were not considered for this table, available on request) based on A, B, and C LoE (see above)*
European Crohn’s and Colitis Organization/European Society of Gastrointestinal and Abdominal Radiology (ECCO/ESGAR): OECBM LoE 1–3 considered
NCCN guidelines provide no separate category for inappropriate use; all guidelines were searched manually for information on inappropriate use/insufficient evidence
BSH, CCO, CNS/AANS, EANM/SNMMI, EFNS, IMWG, RANO/EANO, RCR/RCP, Ryken, and SNMMI/AA: see information above on appropriate use
LoE level of evidence, GoR grade of recommendation
*Mainly due to the large amount, only those recommendation from ACR, CAR, and NCCN with a certain level of recommendation were taken into account
Synthesis of recommendations
Colour coding of recommendations and level of contradictions between the evidence sources for the overall recommendations table
The quality of the included information sources was appraised by appropriate and validated tools, depending on the respective sources. The quality of HTA was assessed via a double-check approach supported by a checklist from the International Network of Agencies for Health Technology Assessment (INAHTA ) of 14 questions answered with “yes”, “partly”, and “no” (no total score). The AGREE II instrument (German version ) was used to assess the quality of EBG. Each guideline was evaluated by three independent reviewers across six domains and a total of 23 items on a seven-point scale. It was determined that reviewers would deviate a maximum of two points in their final evaluations. In the event of a discrepancy of more than two points per item, the questions were discussed and a consensus was reached. The EBG were finally re-evaluated in their entirety resulting in an average score for each guideline. The SR/MA were assessed by two reviewers independently with AMSTAR-2 , comprising a questionnaire consisting of 16 yes/no questions. Discrepancies were resolved by consensus. Overall quality was determined primarily by considering the critical questions (defined by the developers of the instrument ) and by allocating each SR/MA into one of four suggested categories (high, moderate, low, and critically low) . For more details on the methods used, see the full report and the corresponding Appendix C .
(2) Pilot study: evidence-based PET/PET–CT planning
A study was carried out to guide the investment decision for an additional PET–CT scanner in the region of Carinthia in Austria (561,000 inhabitants). First, a needs-assessment based on a data analysis of PET scans was conducted. Diagnoses were coded according to the International Statistical Classification of Diseases and Related Health Problems 10th revision (ICD-10, 2016 ). All PET scans performed from January to September 2017 were retrieved and clustered according to disease diagnosis (e.g., tumour type: C.00; malignant neoplasm of lip) and, if available, to subgroups of indications (e.g., C00.1 external lower lip). The information was then matched to identify recommendations for evidence-based indications or non-indications [see step (1)]. Indications with contradictory recommendations were—due to lack of detailed clinical information—ascribed to the category of dissenting or unclear evidence from HTA and/or guidelines. The categorization as well as the matching with evidence-based indications was performed by two researchers.
(1) Evidence-based indications and recommendations
Results of the evidence selection process
The updated search results in guideline databases and websites and databases of relevant national and supranational societies regarding recommendations (see tables in report ) was compared with the results of the systematic research and the PET–HTA Report 2015, resulting in additional “appropriate use” recommendations from seven professional societies: DGN and the joint collaboration between EANM and SNMMI, RCP/RCR, ACR Appropriateness Criteria®, CAR Referral Guidelines, and two oncology expert networks for guideline development, CCO and NCCN. It also resulted in concrete “not-to-use” recommendations from four societies or databases: ACR, CAR, and the two disinvestment databases Choosing Wisely and NICE Do-not-Do database. Thus, a total of ten HTA, and 234 positive and negative recommendations from professional societies and databases were included, supplemented by the statements from 23 SR/MA.
Evidence on oncological indications
The PET–HTA report (2015) included 35 HTA assessments on 20 oncological indications. In addition, the report update revealed two novel HTA on bronchial carcinoma from the US Agency for Healthcare Research and Quality (AHRQ)  and the HTA-Center for the Västra Götaland Region, Sweden  as well as one HTA each on mamma carcinoma, compiled also by AHRQ , on penile/testicular carcinoma and on bladder/renal cancer, the latter two compiled by the Scottish Health Technologies Group within Healthcare Improvement Scotland (SHTG/HIS [17, 18, 19, 20]). For further oncological indications considered in the PET–HTA report 2015, no more recent HTA was found. Reported endpoints in the included studies used for the HTA reports refer to diagnostic accuracy (mainly tumour grading and change in management).
Recommendations as well as non-recommendations (n = 188) from professional societies (see Box 1 for abbreviations) were retrieved and extracted from AANS/CNS , ACCP , BSH , CCO [24, 25, 26], DGN , IMWG , and RCR/RCP . Three common guidelines, one from SNMMI/EANM and others (ACNM, ACPM, ASCO, CANM, and SPR) , one from RANO/EANO , and one from EANM/SNMMI , were also considered. One guideline (Ryken et al. ) has been elaborated by several universities.
Three guidelines (CCO , RCR/RCP , SNMMI/EANM/others ) provided recommendations for tumours generally as well as for non-oncological indications. Another three guidelines dealt with tumours of the head (DGN , Ryken , RANO/EANO ); two focused on myeloma (BSH , IMWG ); and one guideline addressed prostate cancer (EANM/SNMMI ), anal canal carcinoma (CCO ), lung carcinoma (ACCP ), paraneoplastic syndrome (PNS) (CCO ), and pituitary adenoma (AANS/CNS ), respectively. The recommendations of ACR , CAR  and NCCN  as well as the explicit non-recommendations of choosing Wisely  and NICE Do-not-Do  were also considered.
Moreover, 12 SR/MA for seven oncological sub-indications were included [39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50]; of those, two supplemented an HTA report [49, 50] and all considered diagnostic accuracy as an endpoint, especially for primary diagnosis and staging for pre-treatment/treatment planning. The systematic reviews consisted primarily of retrospective studies.
The quality of the HTA was overall very good, with only a few questions not evaluated with “yes”. The assessment of the quality of the guidelines varied. In domain 1: “scope and purpose” and domain 4: “clarity of presentation”, the guidelines received high ratings and there were fewer variations among the guidelines. Domain 3 (“rigour of development”), which considers the accuracy of guideline development, ranged from 11% (DGN ) to 93% (ACCP ), showing the largest differences among the guidelines. In the overall rating, the ACCP guideline  was given a score of 5.67 (max. 7) and also ranked highest among two domains 3 and 4. The RCR/RCP guideline  attained last place with a mean score of 2.67.
The quality of the SR/MA in terms of overall qualitative assessment (no overall score) revealed that 10 out of 12 were “critically low”. Hence, the SR/MA is used only as supplementary information.
There is a (relative) consensus that there is sufficient evidence for sub-indications in eight indications in favour of PET or PET–CT examinations (in Table 2 highlighted green). The first six were already determined in the 2015 report—(1) bronchial carcinoma (update: mainly pre-treatment, contradictory in re-staging and response control and in therapy monitoring), (2) colon carcinoma, (3) malignant lymphoma, (4) malignant melanoma (update: contradictory for diagnosis of recurrence), (5) mamma carcinoma (treatment response, for diagnosis of recurrence), and (6) head–neck tumours (in 2015 report: CUP, thyroid carcinoma; update: mainly for diagnosis of recurrence)—while two new treatment areas were added by the update: (7) myeloma and (8) neuroendocrine tumours.
There is a (relative) consensus that, in eight other indication areas, there was too little evidence in favour of PET examination (individual decisions possible) (in Table 2 highlighted red): (1) bladder carcinoma, (2) hepatic cancer, (3) cervical carcinoma, (4) gastric cancer, (5) ovarian and (6) uterus carcinoma, (7) prostate cancer, and (8) paraneoplastic neurological syndrome.
For a further set of eight indications, there is contradictory and equivocal evidence and recommendations were developed along with reservations (in Table 2 highlighted yellow or blue): (1) anal canal, (2) brain (especially glioma), (3) testicular, (4) renal, (5) penile carcinoma, (6) esophagus cancer (except re-staging), and (7) pancreatic carcinoma as well as (8) bone and soft-tissue tumour (+ gastrointestinal stromal tumour).
Evidence on neurological indications
Two HTA reports were identified about neurological indications for the use of PET—one from the Australian Medical Services Advisory Committee (MSAC)  looking into Alzheimer’s dementia (AD) and one compiled by the Canadian Agency for Drugs and Technologies in Health (CADTH) on epilepsy . Reported endpoints in the included studies of these HTA reports refer mainly to diagnostic accuracy; no study could be identified that investigates diagnostic effectiveness and safety.
Recommendations and non-recommendations (n = 28) from professional societies (see Box 1 for abbreviations) were retrieved and extracted from CCO [24, 53], EFNS , RCR/RCP , SNMMI/AA , and a common guideline from EANM/SNMMI . RCR/RCP  provides recommendations for several non- and oncological indications. Two further guidelines ([54, 55]) consider Alzheimer’s dementia/dementia (ADD) or AD only, while another guideline (EANM/SNMMI ) presents general recommendations on brain-related disorders (refer to SNMMI/AA ) CCO [24, 53] (two guidelines) which considers epilepsy. In total, three SR/MA were included (for AD) [57, 58, 59]. All consider diagnostic accuracy in terms of primary diagnosis as the endpoint. Primarily, prospective studies were included in the SR/MA.
The quality of the HTA was rated as very good, with only one question not judged as “yes”. The assessment of the quality of the guidelines showed that domains 1 (“scope and purpose”) and 4 (“clarity of presentation”) received very high ratings and are quite consistent. However, in terms of editorial independence, applicability, and accuracy of the guideline development, big differences were observed. In the overall assessment, SNMMI/AA  ranks first; RCR/RCP is in last place . All the SR/MA rated “critically low” in the overall quality assessment (no comprehensive score). As such, the SR/MA are to be used as supplementary information for the overall recommendations.
PET/PET–CT indications (neurology): overall recommendations
There is a (relative) agreement that there is not sufficient evidence in favour of a PET/PET–CT for either of these two sub-indications (in Table 3 highlighted red), though professional societies uniformly/consistently name specific cases of AD or specific patient characteristics that speak for/against the use of PET, depending mainly on the respective tracer (amyloid vs. FDG). These recommendations, however, are only based on one source [55, Update: 60] and the authors themselves acknowledge the limitations, stating that, “At the time of this review, experience with clinical amyloid PET imaging [was] limited. Most published studies to date … [were] designed to validate this technology and understand disease mechanisms rather than to evaluate applications in clinical practice. As a result, published data are available primarily from highly selected populations with prototypical findings rather than from patients with comorbidities, complex histories, and atypical features often seen in clinical practice (e7)” .
Equivocal evidence (e.g., contradictory between HTA and EBG in Table 3, highlighted yellow or blue) was also found for the application of PET/PET–CT in patients having epilepsy (again, only in certain cases, in specialized epilepsy centres), though there is (some) consensus among the professional societies.
Evidence on inflammatory disorders
In total, three HTA could be included about inflammatory disorder indications. One focused on infections in general from CADTH , dating back to 2008, and two other reports (each consists of a scoping report and an advice statement) from SHTG/HIS (2013) focus on pyrexia of unknown origin and sarcoidosis [62, 63, 64, 65]. Reported endpoints in the studies within these HTA reports refer to diagnostic accuracy (mainly for primary diagnosis).
Recommendations and non-recommendations (n = 18) from professional societies (see Box 1 for abbreviations) were retrieved and extracted from ECCO/ESGAR , a common guideline of EANM/SNMMI  and RCR/RCP  who gave recommendations for several non-oncological indications. EANM/SNMMI  gave general recommendations on inflammatory disorders and ECCO/ESGAR  considers inflammatory bowel disease alone. Explicit non-recommendations by Choosing Wisely  or NICE Do-not-Do  were not identified.
In total, eight SR/MA were included for five indications [68, 69, 70, 71, 72, 73, 74, 75]. All but two reviews [68, 69] include a meta-analysis and consider diagnostic accuracy as the primary endpoint.
The quality of the three HTA was rated “very good”, with only a few questions that could not be judged “yes”. And the quality of the three guidelines revealed that domain 3 [on the rigour of the guideline development (including evidence clearly assigned to recommendations)] ranges widely, from 16% (RCR/RCP ) to 55% (ECCO/ESGAR ). Notably, all guidelines were rated 0% with regard to editorial independence (domain 6). The RCR/RCP  guideline scored poorest on in all areas compared to the other two. In the overall rating, ECCO/ESGAR  ranked first of the guidelines and all SR/MA were rated as “critically low”.
PET/PET–CT indications (inflammatory indications): overall recommendations
(2) Pilot study: evidence-based PET/PET–CT planning
In a second step, the recommendations derived from the evidence were applied (matched) to the hospital data on PET scans in one hospital (Carinthia, Austria) to gain an understanding of the PET utilization and capacity needs. Between January and September 2017, 1762 PET scans were conducted at the Clinicum Klagenfurt/Carinthia (KABEG Management: Needs-assessment of PET–CT at the Clinicum Klagenfurt, June 2018, unpublished). Of those, 1370 (77.8%) could be assigned to the three categories (see Tables 1–4) as recommended by evidence-based indications (963, 54.7%), not recommended (311.8%) and contradictory recommendations (376, 21.3%). The other 392 (of 1762, 22.2%) could not be allocated to any of the three treatment areas due to missing information of the diagnostic code or lack of information from recommendations in HTA or clinical guidelines.
PET scans and corresponding ICD-10 category matched to evidence-based recommendations (n = 994), Clinicum Klagenfurt/Carinthia (KABEG Management: Needs-assessment of PET–CT at the Clinicum Klagenfurt, June 2018, unpublished)
Recommended evidence-based indications
(n = 963), n (%)
Not recommended evidence-based indications
(n = 31), n (%)
C15–C26: malignant neoplasms, digestive organs
C30–C39: malignant neoplasms, respiratory system and intrathoracic organs
C43–C44: malignant neoplasms, skin
C50–C58: malignant neoplasms, breast, and female genital organs
C60–C63: malignant neoplasms of male genital organs
C64–C68: malignant neoplasms, urinary organs
C73–C75: malignant neoplasms, endocrine glands, and related structures
C76–C80: malignant neoplasms, secondary and ill-defined
5 (< 1)
C81–C96: malignant neoplasms, stated or presumed to be primary, of lymphoid, haematopoietic and related tissue
D00–D09: in situ neoplasms
D10–D36: benign neoplasms
D37–D48: neoplasms of uncertain or unknown behaviour
G30–G32: other degenerative diseases of the nervous system
2 (< 1)
The majority (22, 70%) of the 31 PET scans not recommended within evidence-based recommendations (see Table 5) were in the following three ICD-10 indications: C64–C68: Malignant neoplasms, urinary organs (10, 32%), C15–C26: malignant neoplasms digestive organs (6, 19%), and C50–C58: malignant neoplasms, breast and female genital organs, respectively (6, 19%).
Summary of findings: (1) evidence-based indications and recommendations
Evidence assessments on PET/PET–CT have been increasingly published over the past two decades in many countries and languages. Taking a 2004–2014 perspective, the PET–HTA 2015 report identified 155 HTA reports to evaluate PET or PET–CT; even with a timeframe of 2008–2014, there were still 82 HTA available. Thirty-five of these were included and extracted for their statements on the use of PET/PET–CT for oncological indications. Five more recent HTA on oncological (sub-)indications were identified during the HTA report update. For the new indications—for neurological and inflammatory disorders—only five HTA could be considered. Recommendations of professional societies (e.g., guidelines) were also updated and explored for the three indications. A total of 234 recommendations were, therefore, included in the updated report. In addition, a total of 23 SR/MA provided supplementary information. Fifteen looked only at oncological indications. Cost-effectiveness of PETs was not an inclusion criterion and was, therefore, not explicitly considered; however, while almost no evidence exists, information was extracted from the reports when there was mention of cost-effectiveness.
In a comparison of HTA results, the tabulated recommendations of professional societies and SR/MA for oncological indications reveal that there is general agreement on “significant” indications (e.g., bronchial carcinoma, and head and neck tumours) for the use of PET/PET–CT. However, there are significant differences in the level of detail of sub-indications and in the approach for when a scan should not be performed. There is also significant variance in the reliance on the access of graded pre-diagnostics.
Mamma carcinoma (now recommended for certain sub-indications such as tumour response assessment for metastatic mamma carcinoma (mainly bone metastases), before: not recommended)
Cervix carcinoma (not recommended, before contradictory)
Testicular, renal, and penis carcinoma (contradictory, before not recommended)
New (not included in the PET–HTA report 2015): myeloma (recommended), neuroendocrine tumours not recommended), anal canal cancer (contradictory)
In the case of neurological indications and inflammatory disorders, there is comparatively more discrepancy in the recommendations of professional societies and between the HTA and professional societies. There is a notable, consistent emphasis on the weak and insufficient evidence base. The SR/MA included in our report demonstrate this: all were considered “critically low” in the quality assessment.
Summary of findings: (2) pilot study on evidence-based PET/PET–CT planning
Based on evidence-based recommended and not recommended indications formulated in step (1) of this study, a first-ever pilot of planning PET capacities was conducted and, as such, has no comparator.
A data-driven needs-assessment was initially conducted to provide a basis for an investment decision around the need for an additional PET–CT scanner in Carinthia, Austria. First, diagnoses were coded according to ICD-10 classifications. Then, the 1762 PET scans performed between January and September 2017 were matched to relevant recommendations for evidence-based indications/non-indications, resulting in 77.8% being assigned to either recommended (54.7%), not recommended (1.8%) or contradictory (21.3%) evidence-based indications. 22.2% could not be ascribed due to missing information of the diagnostic code or lack of information from recommendations in HTA or clinical guidelines. Based on the data analysis and an additional assessment of the utilization as well as occupancy rates, it was decided against the investment in a second PET scanner in Carinthia.
The main strength of the presented work is the rigorous, systematic approach applied in all steps (e.g., double-check principle and quality assessment), complemented a comprehensive, targeted manual search. Nevertheless, the methodical process has some limitations. The systematic synthesis of available evidence, which mainly relies on already aggregated evidence, may result in a certain loss of detailed information. In addition, the primary outcome of interest in the data extraction was the conclusions as articulated by the respective authors, which are different in terms of formulation and meaning and, therefore, difficult to compare. As a result, a trend can be seen in the statements.
Moreover, the multitude of recommendations from professional organizations necessarily led to a capping of the number of sources, meaning that some were not included and important contextual insight may have been lost. For example, the S3 guidelines from the Association of Scientific Medical Societies e.V. (AWMF) in Germany and the guidelines from the Scottish Intercollegiate Guidelines Network (SIGN) were not included as they do not have a specific PET/PET–CT focus. However, they both provide important recommendations as they consider not only “study evidence”, but also detailed aspects of the diagnostic-therapeutic chain and differentiate more comprehensively among tumour entities. That some guidelines were a priori omitted may lead to a potential bias (of the overall picture). Similarly, the heterogeneous quality of the included guidelines may also result in a skewed overall picture of existent recommendations. The summary tables make this transparent by assigning respective recommendations to the corresponding guidelines, referencing, as well, the strength of evidence. Finally, in Tables 2, 3, and 4 of the overall recommendations, a differentiated consideration of tumour entities is lost. Nevertheless, they provide an overall picture that can be useful (see pilot).
Regarding the 22.2% of PET scans in Carinthia, Austria, that could not be assigned to a recommendation in the pilot study, one reason could be the very specific indications found in the evidence or a too detailed coding. In general, while the high number of PET scans that could not be ascribed to any category could be seen as limiting the explanatory/instructive power of the pilot to use evidence-based indication lists as basis for a needs-assessment and investment decisions, it also shows clearly that there is a need for improvement of coding indications within the context of planning of medical services. For the final investment decision, further information on timing and frequency of PET utilization and occupancy rate over full work days and weeks are needed.
Overall, this study has resulted in more detailed information and specifications around PET/PET–CT indications as compared to the 2015 PET–HTA report. This update together with the aggregate list of overall recommendations for indications as well as the explicit non-recommendations from the 2015 PET–HTA report can serve as needs-based and evidence-based decision support for PET/PET–CT service provision in hospitals as evidenced by the pilot study in Austria. A better coding of PET utilization is needed for planning. Furthermore, additional information such as timing, frequency of PET utilization, as well as occupancy rate over full work days and weeks, is also necessary to guide an investment decision.
The support of Helene Eckhardt, Fabian Dressenhöfer, Christian Nam Kai Tran, and Anna Irshad in compiling the HTA report is hereby gratefully acknowledged. We would also like to thank Katherine Polin for the language check.
This study was funded by the German Society for Nuclear Medicine (DGN) who did not have any influence on the content of the report.
Compliance with Ethical Standards
Conflict of interest
All authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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