Effectiveness assessment of non-pharmaceutical interventions: lessons learned from the COVID-19 pandemic.

Effectiveness of non-pharmaceutical interventions (NPIs), such as school closures and stay-at-home orders, during the COVID-19 pandemic has been assessed in many studies. Such assessments can inform public health policies and contribute to evidence-based choices of NPIs during subsequent waves or future epidemics. However, methodological issues and no standardised assessment practices have restricted the practical value of the existing evidence. Here, we present and discuss lessons learned from the COVID-19 pandemic and make recommendations for standardising and improving assessment, data collection, and modelling. These recommendations could contribute to reliable and policy-relevant assessments of the effectiveness of NPIs during future epidemics.

Comparing a Sensor for Movement Assessment with Traditional Physiotherapeutic Assessment Methods in Patients after Knee Surgery-A Method Comparison and Reproducibility Study.

Wearable sensors offer the opportunity for patients to perform a self-assessment of their function with respect to a variety of movement exercises. Corresponding commercial products have the potential to change the communication between patients and physiotherapists during the recovery process. Even if they turn out to be user-friendly, there remains the question to what degree the numerical results are reliable and comparable with those obtained by assessment methods traditionally used. To address this question for one specific recently developed and commercially available sensor, a method comparison study was performed. The sensor-based assessment of eight movement parameters was compared with an assessment of the same parameters based on test procedures traditionally used. Thirty-three patients recovering after arthroscopic knee surgery participated in the study. The whole assessment procedure was repeated. Reproducibility and agreement were quantified by the intra class correlation coefficient. The height of a one-leg vertical jump and the number of side hops showed high agreement between the two modalities and high reproducibility (ICC > 0.85). Due to differences in the set-up of the assessment, agreement could not be achieved for three mobility parameters, but even the correlation was only fair (r < 0.5). Knee stability showed poor agreement. Consequently, the use of the sensor can currently only be recommended for selected parameters. The variation in degree of agreement and reproducibility across different parameters clearly indicate the need for developing corresponding guidance for each new sensor put onto the market.

Assessing the effect of a regional integrated care model over ten years using quality indicators based on claims data - the basic statistical methodology of the INTEGRAL project.

BACKGROUND: The regional integrated health care model "Healthy Kinzigtal" started in 2006 with the goal of optimizing health care and economic efficiency. The INTEGRAL project aimed at evaluating the effect of this model on the quality of care over the first 10 years. METHODS: This methodological protocol supplements the study protocol and the main publication of the project. Comparing quality indicators based on claims data between the intervention region and 13 structurally similar control regions constitutes the basic scientific approach. Methodological key issues in performing such a comparison are identified and solutions are presented. RESULTS: A key step in the analysis is the assessment of a potential trend in prevalence for a single quality indicator over time in the intervention region compared to the corresponding trends in the control regions. This step has to take into account that there may be a common - not necessarily linear - trend in the indicator over time and that trends can also appear by chance. Conceptual and statistical approaches were developed to handle this key step and to assess in addition the overall evidence for an intervention effect across all indicators. The methodology can be extended in several directions of interest. CONCLUSIONS: We believe that our approach can handle the major statistical challenges: population differences are addressed by standardization; we offer transparency with respect to the derivation of the key figures; global time trends and structural changes do not invalidate the analyses; the regional variation in time trends is taken into account. Overall, the project demanded substantial efforts to ensure adequateness, validity and transparency.

The impact of post-procedural complications on reimbursement, length of stay and mechanical ventilation among patients undergoing transcatheter aortic valve implantation in Germany.

BACKGROUND: The impact of various post-procedural complications after transcatheter aortic valve implantation (TAVI) on resource use and their consequences in the German reimbursement system has still not been properly quantified. METHODS: In a retrospective observational study, we use data from the German DRG statistic on patient characteristics and in-hospital outcomes of all isolated TAVI procedures in 2013 (N = 9147). The impact of post-procedural complications on reimbursement, length of stay and mechanical ventilation was analyzed using both unadjusted and risk-adjusted linear and logistic regression analyses. RESULTS: A total of 235 (2.57%) strokes, 583 (6.37%) bleeding events, 474 (5.18%) cases of acute kidney injury and 1428 (15.61%) pacemaker implantations were documented. The predicted reimbursement of an uncomplicated TAVI procedure was €33,272, and bleeding events were associated with highest additional reimbursement (€12,839, p < 0.001), extra length of stay (14.58 days, p < 0.001), and increased likelihood of mechanical ventilation for more than 48 h (OR 17.91, p < 0.001). A more moderate complication-related impact on resource use and reimbursement was found for acute kidney injury (additional reimbursement: €5963, p < 0.001; extra length of stay: 7.92 days, p < 0.001; ventilation >48 h: OR 6.93, p < 0.001) as well as for stroke (additional reimbursement: €4125, p < 0.001; extra length of stay: 4.68 days, p < 0.001; ventilation >48 h: OR 5.73, p < 0.001). Pacemaker implantations, in contrast, were associated with comparably small increases in reimbursement (€662, p = 0.006) and length of stay (3.54 days, p = 0.006) and no impaired likelihood of mechanical ventilation more than 48 h (OR 1.22, p = 0.156). Interestingly, these complication-related consequences remain mostly unchanged after baseline risk-adjustment. CONCLUSIONS: Post procedural complications such as bleeding events, acute kidney injuries and strokes are associated with increased resource use and substantial amounts of additional reimbursement in Germany, which has important implications for decision making outside of the usual clinical sphere.

Good functional outcome in patients suffering fragility fractures of the pelvis treated with percutaneous screw stabilisation: Assessment of complications and factors influencing failure.

BACKGROUND: Low energy pelvic ring fractures in the elderly have traditionally been treated conservatively, a treatment with potential long-term complications and loss of self-independence. Percutaneous screw stabilisation of the posterior pelvic ring is a new treatment modality that enables immediate mobilisation. The aim of this study was to assess the functional outcome after sacroiliac stabilisation in the elderly. METHODS: All elderly patients with a surgically stabilised low energy pelvic fracture between 2010 and 2015 were included. In 2016 a radiographic follow up and functional test was performed at least one year postoperative. RESULTS: The 50 operated patients had a mean age of 79 years and a one-year mortality of 10% (5/50). Only six patients lost independency after the pelvic fracture and moved to nursing home. The mean Timed Up and Go test was 16s at follow-up. The operation of the posterior pelvic ring averaged 63min with a radiation equal to a diagnostic pelvic CT. One intra-foraminally placed screw was immediately removed and 9 patients were later re-operated on due to symptomatic loosening of one or more screws. No loosening of screws was seen in 11 patients where both S1 and S2 were stabilised and out of 23 trans-sacral screws (crossing both sacroiliac joints) only two loosened. DISCUSSION: CT guided stabilisation of the posterior pelvis is safe and most patients resumed good function and independent living. The risk of a revision operation was 20%, but trans-sacral screw stabilisation in both S1 and S2 could reduce the risk of implant loosening.

Aortic atheroma as a source of stroke - assessment of embolization risk using 3D CMR in stroke patients and controls.

BACKGROUND: It was our purpose to identify vulnerable plaques in the thoracic aorta using 3D multi-contrast CMR and estimate the risk of cerebral embolization using 4D flow CMR in cryptogenic stroke patients and controls. METHODS: One hundred patients (40 with cryptogenic stroke, 60 ophthalmologic controls matched for age, sex and presence of hypertension) underwent a novel 3D multi-contrast (T1w, T2w, PDw) CMR protocol at 3 Tesla for plaque detection and characterization within the thoracic aorta, which was combined with 4D flow CMR for mapping potential embolization pathways. Plaque morphology was assessed in consensus reading by two investigators and classified according to the modified American-Heart-Association (AHA) classification of atherosclerotic plaques. RESULTS: In the thoracic aorta, plaques <4 mm thickness were found in a similar number of stroke patients and controls [23 (57.5%) versus 33 (55.0%); p = 0.81]. However, plaques ≥4 mm were more frequent in stroke patients [22 (55.0%) versus 10 (16.7%); p < 0.001]. Of those patients with plaques ≥4 mm, seven (17.5%) stroke patients and two (3.3%) controls (p < 0.001) had potentially vulnerable AHA type VI plaques. Six stroke patients with vulnerable AHA type VI plaques ≥4 mm had potential embolization pathways connecting the plaque, located in the aortic arch (n = 3) and proximal descending aorta (n = 3), with the individual territory of stroke, which made them the most likely source of stroke in those patients. CONCLUSIONS: Our findings underline the significance of ≥4 mm thick and vulnerable plaques in the aortic arch and descending aorta as a relevant etiology of stroke. CLINICAL TRIAL REGISTRATION: Unique identifier: DRKS00006234 ; date of registration: 11/06/2014.

Two-year post-discharge costs of care among patients treated with transcatheter or surgical aortic valve replacement in Germany.

BACKGROUND: This study presents data on post-discharge costs of care among patients treated with transcatheter or surgical aortic valve replacement over a two year period. METHODS: Based on a prospective clinical trial, post-discharge utilization of health services and status of assistance were collected for 151 elderly patients via 2250 monthly telephone interviews, valued using standardized unit costs and analysed using two-part regression models. RESULTS: At month 1 post-discharge, total costs of care are substantially elevated (monthly mean: €3506.7) and then remain relatively stable over the following 23 months (monthly mean: €622.3). As expected, the majority of these costs are related to in-hospital care (~98% in month 1 post-discharge and ~72% in months 2-24). Patients that died during follow-up were associated with substantially higher cost estimates of in-hospital care than those surviving the two-year study period, while patients' age and other patient characteristics were of minor relevance. Estimated costs of outpatient care are lower at month 1 than during the rest of the study period, and not affected by the event of death during follow-up. The estimated costs of nursing care are, in contrast, much higher in year 2 than in year 1 and differ substantially by gender and type of procedure as well as by patients' age. Overall, these monthly cost estimates add up to €10,352 for the first and €7467.6 for the second year post-discharge. CONCLUSIONS: Substantial cost increases at month 1 post-discharge and in case of death during follow-up are the main findings of the study, which should be taken into account in future economic evaluations on the topic. Application of standardized unit costs in combination with monthly patient interviews allows for a far more precise estimate of the variability in post-discharge health service utilization in this group of patients than the ones given in previous studies. TRIAL REGISTRATION: German Clinical Trial Register Nr. DRKS00000797 .

Value-based and benefit-based strategies in deciding to bring a test into use should be distinguished.

BACKGROUND: Regulatory and health technology assessment agencies have commented differently on the question whether results from enrichment studies can be used to justify to bring a test into use. We try to provide a framework to discuss this issue. RESULTS: Mathematical definitions for the value and the benefit of a new diagnostic test are given. The possible conclusions about value and benefit from enrichment studies and interaction studies are explored. The terms benefit-based strategy and value-based strategy are introduced. Several potential consequences of using one of the two strategies in deciding to bring a test into use are identified and quantified. Interaction designs allow to assess benefit and value. Enrichment designs allow only to assess benefit. However, it is often probable that interaction studies allow no firm conclusions about the value. The advantage of a benefit-based strategy stems mainly from allowing test-positive patients earlier or even ever to benefit. The main disadvantage is a potential delay in detecting tests of no value. CONCLUSIONS: Benefit-based strategies are preferable if the risk of off-label use and of delayed decisions on the value of a test can be limited. Otherwise, the superiority depends highly on research practice.

Cost-effectiveness of chiropractic care versus self-management in patients with musculoskeletal chest pain.

AIMS: To assess whether primary sector healthcare in the form of chiropractic care is cost-effective compared with self-management in patients with musculoskeletal chest pain, that is, a subgroup of patients with non-specific chest pain. METHODS AND RESULTS: 115 adults aged 18-75 years with acute, non-specific chest pain of musculoskeletal origin were recruited from a cardiology department in Denmark. After ruling out acute coronary syndrome and receiving usual care, patients with musculoskeletal chest pain were randomised to 4 weeks of community-based chiropractic care (n=59) or to a single information session aimed at encouraging self-management as complementary to usual care (n=56). Data on resource use were obtained from Danish national registries and valued from a societal perspective. Patient cost and health-related quality-adjusted life years (QALYs; based on EuroQol five-dimension questionnaire (EQ-5D) and Short Form 36-item Health Survey (SF-36)) were compared in cost-effectiveness analyses over 12 months from baseline. Mean costs were €2183 lower for the group with chiropractic care, but not statistically significant (95% CI -4410.5 to 43.0). The incremental cost-effectiveness ratio suggested that chiropractic care was cost-effective with a probability of 97%, given a threshold value of €30 000 per QALY gained. In both groups, there was an increase in the health-related quality of life, and the mean increases were similar over the 12-month evaluation period. The mean differences in QALYs between the groups were negligible. CONCLUSIONS: Chiropractic care was more cost-effective than self-management. Therefore, chiropractic care can be seen as a good example of a targeted primary care approach for a subgroup of patients with non-specific chest pain. TRIAL REGISTRATION NUMBER: NCT00462241.

A framework to assess the value of application of formal criteria to check clinical relevance in RCTs as part of a benefit assessment strategy.

Recently, the topic of assessing clinical relevance on top of statistical significance in the analysis of randomized control trials (RCTs) has got increasing attention, in particular as part of benefit assessments. Several formal criteria to serve this purpose have been published. In this paper, we present a framework to assess the value of the application of such criteria. We propose to quantify the need for the assessment of clinical relevance by the actual risk of having accepted a benefit for a treatment with an irrelevant effect in a successful RCT. We then study how this risk can be controlled by two popular criteria based on comparing the effect estimate or the lower bound of the confidence interval with a given threshold. We further propose to quantify the impact of using formal criteria by considering the expected costs when specifying error-specific costs for each of the three possible types of errors: A benefit may be accepted for a treatment, which is actually inferior, or which is not inferior, but only implies an irrelevant improvement, or a benefit may be rejected for a treatment implying a relevant improvement. This way we can demonstrate that the impact depends on parameters which are typically not explicitly defined in the frame of benefit assessments. Depending on the values of these parameters, formal checks of clinical relevance may imply better decisions on average, but they may also imply more harm than good on average.

In-hospital resource utilization in surgical and transcatheter aortic valve replacement.

BACKGROUND: Little is known about preoperative predictors of resource utilization in the treatment of high-risk patients with severe symptomatic aortic valve stenosis. We report results from the prospective, medical-economic "TAVI Calculation of Costs Trial". METHODS: In-hospital resource utilization was evaluated in 110 elderly patients (age ≥ 75 years) treated either with transfemoral (TF) or transapical (TA) transcatheter aortic valve implantation (TAVI, N = 83), or surgical aortic valve replacement (AVR, N = 27). Overall, 22 patient-specific baseline parameters were tested for within-group prediction of resource use. RESULTS: Baseline characteristics differed between groups and reflected the non-randomized, real-world allocation of treatment options. Overall procedural times were shortest for TAVI, intensive care unit (ICU) length of stay (LoS) was lowest for AVR. Length of total hospitalization since procedure (THsP) was lowest for TF-TAVI; 13.4 ± 11.4 days as compared to 15.7 ± 10.5 and 21.2 ± 15.4 days for AVR and TA-TAVI, respectively. For TAVI and AVR, EuroScore I remained the main predictor for prolonged THsP (p <0.01). Within the TAVI group, multivariate regression analyses showed that TA-TAVI was associated with a substantial increase in THsP (55 to 61 %, p <0.01). Additionally, preoperative aortic valve area (AVA) was identified as an independent predictor of prolonged THsP in TAVI patients, irrespective of risk scores (p <0.05). CONCLUSIONS: Our results demonstrate significant heterogeneity in patients baseline characteristics dependent on treatment and corresponding differences in resource utilization. Prolonged ThsP is not only predicted by risk scores but also by baseline AVA, which might be useful in stratifying TAVI patients. TRIAL REGISTRATION: German Clinical Trial Register Nr. DRKS00000797.

Duplex ultrasound assessment of native stenoses in the superficial femoral and popliteal arteries: a comparative study examining the influence of multisegment lesions.

PURPOSE: To evaluate duplex ultrasonography (DUS) in the assessment of femoropopliteal stenoses comparing a single native stenosis (SNS) to multisegmental native stenoses (MNS). METHODS: Among the 1284 patients treated for atherosclerotic occlusive disease involving the femoropopliteal segment between November 2002 and November 2012, 139 patients (97 men; mean age 68±8 years) with 142 SNS or 143 MNS in 79 and 60 patients, respectively, were eligible for this retrospective analysis. The peak systolic velocity ratios with proximal (PSVRprox) and distal (PSVRdist) reference for the 285 lesions were compared with their respective angiographic stenosis grade as measured by 2 independent readers using quantitative vascular analysis to ensure objectivity. Receiver operating characteristic curve analysis was used to evaluate sensitivity, specificity, and the optimal thresholds of PSV and PSVR for detection of stenoses by grade (>50%, >70%, or >80% diameter stenosis). The area under the curve (AUC) values of dependent and independent receiver operating characteristic curves were compared. RESULTS: For SNS, correlation of PSVRprox to diameter stenosis (R=0.88) was higher (p<0.001) than the correlation for MNS (R=0.78). In the SNS group, the AUC for detecting a >50% (0.99±0.01), >70% (0.98±0.01), and >80% (0.96±0.01) stenosis with PSVRprox was significantly higher than in the MNS group [AUC50% 0.93±0.02 (p=0.01), AUC70% 0.92±0.02 (p=0.02), and AUC80% 0.87±0.03 (p=0.003)]. The optimal thresholds for detecting >50%, >70%, and >80% stenoses for SNS using PSVRprox were 2.6, 3.3, and 3.9, respectively. For MNS, the optimal thresholds of PSVRprox were 2.6, 3.4, and 3.9, respectively, with respective sensitivities of 87%, 81%, and 75%; respective specificities of 93%, 90%, and 82%; negative predictive values of 45%, 64%, and 74%; and positive predictive values of 99%, 95%, and 83%. CONCLUSION: DUS is an optimal tool for quantification of SNS. However, a multisegment setting has a significant negative impact on the quantification of femoropopliteal artery stenosis.

[Benefit assessment of diagnostic procedures: quo vadimus?]. / Nutzenbewertung diagnostischer Maßnahmen - quo vadimus?

Not only therapeutic procedures, but also diagnostic procedures, have to demonstrate their patient-relevant benefits if they are to be reimbursed by public health insurance. Randomized trials comparing two diagnostic procedures allow us to assess these benefits directly if appropriate outcomes are used. However, owing to the widespread lack of such studies, it is now necessary to use the "linked evidence" approach as well, trying to predict the patient-relevant benefits from the results of comparative accuracy studies. Such a prediction is based on explicitly specifying our expectations with regard to the consequences of a change in diagnosis at the level of a single patient. We discuss the basic properties of these two approaches, which are relevant to the understanding of their possible role in the benefit assessment of diagnostic procedures. We try to predict the future roles of the two approaches and outline some of the issues on which a consensus is required to allow their successful use in benefit assessment. Furthermore, we indicate some of the developments related to the paradigm of individualized care that may influence the use of benefit assessments for diagnostic studies in the future.

Analysis of the additional costs of clinical complications in patients undergoing transcatheter aortic valve replacement in the German Health Care System.

BACKGROUND: This study aims at analyzing complication-induced additional costs of patients undergoing transcatheter aortic valve replacement (TAVR). METHODS: In a prospective observational study, a total of 163 consecutive patients received either transfemoral (TF-, n=97) or transapical (TA-) TAVR (n=66) between February 2009 and December 2012. Clinical endpoints were categorized according to VARC-2 definitions and in-hospital costs were determined from the hospital perspective. Finally, the additional costs of complications were estimated using multiple linear regression models. RESULTS: TF-TAVR patients experienced significantly more minor access site bleeding, major non-access site bleeding, minor vascular complications, stage 2 acute kidney injury (AKI) and permanent pacemaker implantation. Total in-hospital costs did not differ between groups and were on average €40,348 (SD 15,851) per patient. The average incremental cost component of a single complication was €3438 (p<0.01) and the estimated cost of a TF-TAVR without complications was €34,351. The complications associated with the highest additional costs were life-threatening non-access site bleeding (€47,494; p<0.05), stage 3 AKI (€20,468; p<0.01), implantation of a second valve (€16,767; p<0.01) and other severe cardiac dysrhythmia (€10,611 p<0.05). Overall, the presence of complication-related in-hospital mortality increased costs. CONCLUSIONS: Bleeding complications, severe kidney failure, and implantation of a second valve were the most important cost drivers in our TAVR patients. Strategies and advances in device design aimed at reducing these complications have the potential to generate significant in-hospital cost reductions for the German Health Care System.

Cost-effectiveness of PET and PET/computed tomography: a systematic review.

The development of clinical diagnostic procedures comprises early-phase and late-phase studies to elucidate diagnostic accuracy and patient outcome. Economic assessments of new diagnostic procedures compared with established work-ups indicate additional cost for 1 additional unit of effectiveness measure by means of incremental cost-effectiveness ratios when considering the replacement of the standard regimen by a new diagnostic procedure. This article discusses economic assessments of PET and PET/computed tomography reported until mid-July 2014. Forty-seven studies on cancer and noncancer indications were identified but, because of the widely varying scope of the analyses, a substantial amount of work remains to be done.

"Heart Team" decision making in elderly patients with symptomatic aortic valve stenosis who underwent AVR or TAVI - a look behind the curtain. Results of the prospective TAVI Calculation of Costs Trial (TCCT).

AIMS: Little is known about how "Heart Team" treatment decisions among patients suitable for either surgical aortic valve replacement (AVR) or transcatheter aortic valve implantation (TAVI) are made under routine conditions. METHODS AND RESULTS: The "Heart Team" decision-making process was analysed with respect to124 patients of a non-randomised prospective clinical trial that included patients aged ≥75 years: 41 patients underwent AVR and 83 underwent TAVI. By use of the non-parametric classification and regression tree (CART) methodology, 21 baseline parameters were tested to reconstruct the decision process retrospectively. Next, multivariate logistic and Cox regression models were fitted to evaluate the decision and outcome relevance (two-year survival) of the parameters as identified in the CART procedure. For patients with a baseline EuroSCORE I ≥13.48%, no further cut-off points were identified and the majority of these patients underwent TAVI. Among patients with a baseline EuroSCORE I <13.48%, age and left ventricular ejection fraction (LVEF) were identified as further relevant decision parameters. The decision relevance of EuroSCORE I (p=0.003), age (p=0.024) and LVEF (p=0.047) were confirmed by multivariate analysis; however, outcome relevance can be confirmed for EuroSCORE I (p=0.015) only, while treatment decision (TAVI or AVR) was not a significant predictor of mortality (p=0.655). CONCLUSIONS: Despite or even because of the systematic risk selection according to EuroSCORE I values, we observed two-year survival rates of about 75% regardless of whether the patient received TAVI or AVR, suggesting that the decisions made by the "Heart Team" were appropriate.

Hybrid CT angiography and quantitative 15O-water PET for assessment of coronary artery disease: comparison with quantitative coronary angiography.

PURPOSE: CT angiography (CTA) can rule out significant stenoses with a very high reliability, whereas its ability to confirm significant stenoses is suboptimal. In contrast, measurements of myocardial blood flow (MBF) provide information on the haemodynamic consequences of stenoses. Therefore, a combination of the two might improve diagnostic accuracy. We conducted a head-to-head comparison of CTA, measurement of MBF by (15)O-water PET, and hybrid PET/CTA for the detection of significant coronary artery stenoses. METHODS: The study group comprised 44 outpatients scheduled for invasive coronary angiography (ICA) with an intermediate pretest likelihood of coronary artery disease. The patients underwent 64-slice CTA and baseline and hyperaemic PET before ICA with quantitative coronary angiography analysis. RESULTS: On a per-patient basis, the negative predictive values (NPV; 95% confidence intervals in parentheses) were 88 % (64 - 97%) for CTA, 90% (71 - 97%) for PET and 92% (74 - 98%) for PET/CTA, and the positive predictive values (PPV) were 71% (53 - 85%) for CTA, 87% (68 - 95%) for PET and 100% (84 - 100%) for PET/CTA. Similarly, on a per-vessel basis the NPVs (which were generally high) were 97% (94 - 100%) for CTA, 95 % (90 - 99%) for PET and 97% (95 - 100%) for PET/CTA, and the PPVs (which were lower, but higher with PET/CTA) were 53% (39 - 66%) for CTA, 53 % (40 - 66%) for PET and 85 % (73 - 97%) for PET/CTA. In six patients, CTA analysis was hampered by the presence of severe calcifications. However, with the addition of the PET data, all six patients were correctly categorized. CONCLUSION: Cardiac quantitative hybrid PET/CTA imaging has better diagnostic accuracy than CTA alone and PET alone. CTA has a suboptimal PPV, suggesting that hybrid PET/CTA imaging should be used to assess the significance of coronary stenoses diagnosed by CTA.

Generating evidence for clinical benefit of PET/CT in diagnosing cancer patients.

For diagnostic methods such as PET/CT, not only diagnostic accuracy but also clinical benefit must be demonstrated. However, there is a lack of consensus about how to approach this task. Here we consider 6 clinical scenarios to review some basic approaches to demonstrating the clinical benefit of PET/CT in cancer patients: replacement of an invasive procedure, improved accuracy of initial diagnosis, improved accuracy of staging for curative versus palliative treatment, improved accuracy of staging for radiation versus chemotherapy, response evaluation, and acceleration of clinical decisions. We also develop some guidelines for the evaluation of clinical benefit. First, it should be clarified whether there is a direct benefit of the use of PET/CT or an indirect benefit because of improved diagnostic accuracy. If there is an indirect benefit, then decision modeling should be used initially to assess the benefit expected from the use of PET/CT. Only if decision modeling does not allow definitive conclusions should randomized controlled trials be planned.