Study design for concurrent development, assessment, and implementation of new diagnostic imaging technology

With current constraints on health care resources and emphasis on value for money, new diagnostic imaging technologies must be assessed and their value demonstrated. The state of the art in the field of diagnostic imaging technology assessment advocates a hierarchical step-by-step approach. Although rigorous, such a hierarchical assessment is time-consuming, and, given the current rapid advances in technology, results are often too late to influence management and policy decisions. The purpose of this article is to discuss a study design in which development, assessment, and implementation of new diagnostic imaging technology take place concurrently in one integrated process. An empirically based pragmatic study design is proposed for imaging technology assessment. To minimize bias and enable comparison with current technology, a randomized controlled design is used whenever feasible and ethical. Outcome measures should reflect the clinical decision-making process based on imaging information and acceptance of the new test. Outcome measures can include additional imaging studies requested, costs of diagnostic work-up and treatment, physicians' confidence in therapeutic decision making, recruitment rate, and patient outcome measures related to the clinical problem. The key feature of the proposed study design is analysis of trends in outcome measures over time.     

Clinical decision rules in radiology

Clinical decision rules to guide physicians in the appropriate use of diagnostic imaging studies need to be developed, in part, to control the overutilization of imaging studies. These rules need to be evidence based. Randomized control trials can be designed to assess the value of imaging studies and interventional procedures at levels five and six, patient outcome and societal efficacies, in Fryback and Thornbury's hierarchical model of efficacy. Results of these trials can be used to develop clinical decision rules. However, the efficacy of most diagnostic imaging studies can be assessed better at levels three and four, diagnostic thinking and therapeutic efficacies. Studies can be designed to determine clinical situations in which imaging studies will be of no value or to determine clinical criteria for the use of imaging studies. Systematic reviews of the literature and other techniques of analysis of evidence, such as decision trees, also can be used to develop evidence-based clinical decision rules for the use of diagnostic imaging procedures.     

Evidence-based risk assessment in noninvasive imaging.

Assessment of important clinical and economic outcomes has become central to the evaluation of patient care. Outcome research is deeply rooted in epidemiology, including the use of multivariable, risk-adjusted regression analysis. In our current health care environment, these methods are increasingly being used to assess the quality of care and to profile physicians and laboratories. Nuclear medicine physicians therefore need to better understand outcome methodologies in order to evaluate patient outcomes, develop guidelines, and decide on patient management. METHODS: This review describes the methods of assessing the diagnostic and prognostic value of nuclear medicine techniques and, briefly, the methodologic limitations of sample size, frequency and type of events, and follow-up periods and the incremental value of imaging. Also described are logistic regression and Cox proportional hazards modeling. Models for risk assessment are designed to identify whether patients require conservative (i.e., low-risk) or aggressive (i.e., high-risk) treatment. Treatment selection is currently based on risk assessment and the formation of an integrated, empiric risk stratification algorithm of care. This review also includes the methods of assessing economic effectiveness and quality-of-life issues for patients examined with nuclear medicine techniques. CONCLUSION: In this era of constrained resources, low-cost outpatient-based care may be of increasing importance. High-quality evidence of the clinical and economic outcome of nuclear imaging is essential for helping health care providers and payers assess its value.     

Changes in the approval process for contrast media.

This paper discusses, from an academic perspective, the changes proposed by the Food and Drug Administration (FDA) regarding the approval process for contrast media. The proposed changes are extensive, covering indications, safety and efficacy assessments, and image acquisition and handling. The draft guidance unfortunately grouped together therapeutics and diagnostics. Indications were divided into the following categories: a) structure delineation, b) functional physiological, or biochemical assessment, c) disease or pathology detection/assessment, and d) diagnostic or therapeutic patient management. Such a division would greatly complicate the approval process, requiring multiple trials to gain approval. The draft guidance also disregarded that indications for imaging agents are often general and not disease specific. As issued, it implied that separate trials would be required for each clinical setting where lesions might be important. As the standard of truth, blinded reads with no clinical information were proposed as the primary endpoint. This ignores how diagnostic exams are interpreted and the value of medical history.     

Utility evaluations for Markov states of lung cancer for PET-based disease management.

BACKGROUND: Utilities for the health outcomes states (Markov states) of non-small cell lung carcinoma (NSCLC) should be measured to evaluate management options for patients because patients are key participants in the process of care, and their assessment of diagnostic and therapeutic value in the options presented to them ultimately impacts their net health outcomes. This investigation sought to measure utilities for stage-dependent outcomes states of NSCLC. METHODS: Persons (n = 23) with suspected NSCLC based on physical findings and computed tomography completed a short utilities survey. Utility valuations were obtained according to severity of morbidity and varied considerably. Respondents rated these health states according to accuracy measures for 18flurodeoxyglucose (18FDG) positron emission tomography (PET) imaging and medastinoscopy. RESULTS: The results demonstrate that stage-dependent morbidity is an important consideration for patients with NSCLC and should be included in any decision analysis regarding the evaluation or treatment of NSCLC. Respondents valued the quality of information obtained from non-invasive PET and invasive mediastinoscopy comparably. The utilities obtained from this investigation are useful in clinical decision-making based on Markov processes because they provide an initial estimation of utility assessment for 18FDG-based diagnostic evaluation of lung cancer. CONCLUSIONS: Consequently, these utilities will be useful in future decision analyses that require patient preference in the assignment of the evaluation of decision options (branches).     

Technology assessment--an American view.

Technology assessment of an imaging method such as magnetic resonance (MR) is a complicated concept that includes aspects of epidemiology, biostatistics, clinical efficacy determination, outcomes assessment, and knowledge of the technical and medical bases of the imaging method under study. To enhance understanding of the interrelations of the different aspects of technology assessment, a hierarchical model is proposed. This extends from the basic imaging physics domain through clinical applications in diagnosis and treatment decisions to patient outcomes and ultimately societal considerations. This overview paper presents the conceptual continuum of the hierarchical model, and then describes the interrelationships among efficacy, cost effectiveness, and outcomes research as components embedded within the context of technology assessment. It also points out how scientific quality of research in MR imaging assessment can be enhanced through improved research design that takes into account basic concepts of the model.     

Clinical and economic outcomes assessment in nuclear cardiology.

The future of nuclear medicine procedures, as understood within our current economic climate, depends upon its ability to provide relevant clinical information at similar or lower comparative costs. With an ever-increasing emphasis on cost containment, outcome assessment forms the basis of preserving the quality of patient care. Today, outcomes assessment encompasses a wide array of subjects including clinical, economic, and humanistic (i.e., quality of life) outcomes. For nuclear cardiology, evidence-based medicine would require a threshold level of evidence in order to justify the added cost of any test in a patient's work-up. This evidence would include large multicenter, observational series as well as randomized trial data in sufficiently large and diverse patient populations. The new movement in evidence-based medicine is also being applied to the introduction of new technologies, in particular when comparative modalities exist. In the past 5 years, we have seen a dramatic shift in the quality of outcomes data published in nuclear cardiology. This includes the use of statistically rigorous risk-adjusted techniques as well as large populations (i.e., > 500 patients) representing multiple diverse medical care settings. This has been the direct result of the development of multiple outcomes databases that have now amassed thousands of patients worth of data. One of the benefits of examining outcomes in large patient datasets is the ability to assess individual endpoints (e.g., cardiac death) as compared with smaller datasets that often assess combined endpoints (e.g., death, myocardial infarction, or unstable angina). New technologies for the diagnosis of coronary artery disease have contributed to the rising costs of care. In the United States and in Europe, costs of care have risen dramatically, consuming an ever-increasing amount of available resources. The overuse of diagnostic angiography often leads to unnecessary revascularization that does not lead to improvement in outcome. Thus, the potential exists that stress SPECT imaging, a highly effective diagnostic tool, could effect substantial change in reducing inappropriate use of an invasive procedure resulting in cost effective cardiac care. A synthesis of current economic evidence in gated SPECT imaging will be presented. In conclusion, a current state of the evidence review is presented on the clinical and economic data using nuclear cardiology imaging.     

Imaging readouts as biomarkers or surrogate parameters for the assessment of therapeutic interventions

Surrogate markers and biomarkers based on imaging readouts providing predictive information on clinical outcome are of increasing importance in the preclinical and clinical evaluation of novel therapies. They are primarily used in studies designed to establish evidence that the therapeutic principle is valid in a representative patient population or in an individual. A critical step in the development of (imaging) surrogates is validation: correlation with established clinical endpoints must be demonstrated. Biomarkers must not fulfill such stringent validation criteria; however, they should provide insight into mechanistic aspects of the therapeutic intervention (proof-of-mechanism) or document therapy efficacy with prognostic quality with regard to the long-term clinical outcome (proof of concept). Currently used imaging biomarkers provide structural, physiological and metabolic information. Novel imaging approaches annotate structure with molecular signatures that are tightly linked to the pathophysiology or to the therapeutic principle. These cellular and molecular imaging methods yield information on drug biodistribution, receptor expression and occupancy, and/or intra- and intercellular signaling. The design of novel target-specific imaging probes is closely related to the development of the therapeutic agents and should be considered early in the discovery phase. Significant technical and regulatory hurdles have to be overcome to foster the use of imaging biomarkers for clinical drug evaluation.     

Cost-effectiveness analysis in the assessment of diagnostic imaging technologies

In many ways, diagnostic technologies differ from therapeutic medical technologies. Perhaps most important, diagnostic technologies do not generally directly affect long-term patient outcomes. Instead, the results of diagnostic tests can influence the care of patients; in that way, diagnostic tests may affect long-term outcomes. Because of this, the benefits associated with the use of a specific diagnostic technology will depend on the performance characteristics (eg, sensitivity and specificity) of the test, as well as other factors, such as prevalence of disease and effectiveness of available treatments for the disease in question. The fact that diagnostic tests affect short-term, or "surrogate," outcomes, rather than long-term patient outcomes makes evaluation of these tests more complicated than the evaluation of therapeutic technologies. This article will trace the history of technology assessment in medicine, address the role of cost-effectiveness and decision analysis in health technology assessment, and describe unique features and approaches to assessing diagnostic technologies. The article will then conclude with a consideration of the limits of medical technology assessment.     

The implications of patient antibody response for the clinical usefulness of immunoscintigraphy

The evolving clinical role for tumour immunoscintigraphy appears to be in monitoring patients for metastatic spread and tumour recurrence. Such diagnostic strategies inevitably involve repeat imaging investigations, and therefore the probability of patient immunization against the administered radiopharmaceutical is increased. Patient antibody responses would appear to affect the quality and sensitivity of repeat imaging studies, and this also has implications for the therapeutic efficacy of subsequent therapy doses. A simple test for determining patient sensitization to antibody is required.     

Precision imaging—its impact on image quality and diagnostic confidence in breast ultrasound examinations

Objective:

To determine the effect of noise-reducing innovation—precision imaging (PI)—on image quality and diagnostic efficacy in breast ultrasound.

Methods:

The study, which assessed four levels of PI from zero to three, consisted of two parts: image quality assessment and diagnostic efficacy evaluation. For the first part, 247 sets of ultrasound images displayed at each PI level were evaluated by 6 experienced breast imaging observers, by rating image quality using visual grading analysis on a 1–4 scale. For the diagnostic efficacy part 51 breast lesions were displayed at each PI level and scored 1–6 to generate a receiver operating characteristic (ROC) curve. These images were evaluated by radiologists and sonographers. Analyses were performed using non-parametric Friedman and Wilcoxon signed rank tests and a multireader multicase methodology.

Results:

Statistically, higher scores of image quality were observed with increased levels of PI than with the zero setting (p < 0.001). The ROC analysis did not demonstrate any significant change in diagnostic efficacy, with mean scores for all observers being 0.79, 0.80, 0.81 and 0.81 for settings zero, one, two and three, respectively.

Conclusion:

This study suggested a perceived improvement in image quality with increasing levels of PI; however, no changes in diagnostic efficacy were noted. The importance of looking at the impact of new imaging technologies in a multifaceted way is emphasized.

Advances in knowledge:

To our knowledge, this is the first article investigating the impact of the PI algorithm on ultrasound image quality and breast lesion characterization.     

MR imaging of soft-tissue vascular malformations: diagnosis, classification, and therapy follow-up

Vascular malformations and tumors comprise a wide, heterogeneous spectrum of lesions that often represent a diagnostic and therapeutic challenge. Frequent use of an inaccurate nomenclature has led to considerable confusion. Since the treatment strategy depends on the type of vascular anomaly, correct diagnosis and classification are crucial. Magnetic resonance (MR) imaging is the most valuable modality for classification of vascular anomalies because it accurately demonstrates their extension and their anatomic relationship to adjacent structures. A comprehensive assessment of vascular anomalies requires functional analysis of the involved vessels. Dynamic time-resolved contrast material-enhanced MR angiography provides information about the hemodynamics of vascular anomalies and allows differentiation of high-flow and low-flow vascular malformations. Furthermore, MR imaging is useful in assessment of treatment success and establishment of a long-term management strategy. Radiologists should be familiar with the clinical and MR imaging features that aid in diagnosis of vascular anomalies and their proper classification. Furthermore, they should be familiar with MR imaging protocols optimized for evaluation of vascular anomalies and with their posttreatment appearances. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.315105213/-/DC1.     

Morton neuroma: effect of MR imaging findings on diagnostic thinking and therapeutic decisions.

PURPOSE: To determine the effect of magnetic resonance (MR) imaging results on diagnostic thinking and therapeutic decisions by orthopedic surgeons in cases of a possible Morton neuroma. MATERIAL AND METHODS: Orthopedic surgeons completed a questionnaire before and after MR imaging for 54 feet in 49 patients thought to have Morton neuroma. Clinical diagnosis (Morton neuroma, differential diagnosis), location, diagnostic confidence, and therapeutic decisions were noted before and after MR imaging. The influence of the size of the neuroma on therapeutic decisions was analyzed. MR imaging diagnoses were compared with surgical results for 23 revised intermetatarsal spaces. RESULTS: After MR imaging, the clinical diagnosis of Morton neuroma was withdrawn in 15 of 54 (28%) feet. In 14 of 39 maintained diagnoses, the location or number of neuromas was changed after MR imaging. Confidence levels for Morton neuroma increased substantially after MR imaging. In 31 (57%) feet, a change in treatment plan resulted after MR imaging. Diameters of neuromas on MR images were significantly larger (P = .003) in surgically treated feet than in conservatively treated feet. MR imaging diagnoses were correct in all 23 revised intermetatarsal spaces. CONCLUSION: MR imaging has a major effect on diagnostic thinking and therapeutic decisions by orthopedic surgeons when Morton neuroma is suspected, especially because MR imaging helps in localization and size assessment of Morton neuromas.     

Uterine Artery Embolization for Symptomatic Adenomyosis: Proceedings from a Society of Interventional Radiology Foundation Research Consensus Panel

Adenomyosis poses an important diagnostic and therapeutic challenge in women’s health because of a variety of clinical/imaging presentations and frequent coexistence with other benign gynecologic conditions. In recent years, uterine artery embolization (UAE) for the treatment of adenomyosis has shown encouraging and favorable outcomes and long-term symptom improvement. To expand the current understanding of adenomyosis pathophysiology, imaging diagnostic criteria, and treatment outcomes, the Society of Interventional Radiology Foundation gathered a multidisciplinary Research Consensus Panel with experts from diverse backgrounds. The topics addressed were centered around the following: (i) the clinical presentation and imaging findings to diagnose adenomyosis; (ii) the currently available medical, interventional, and surgical treatment options; and (iii) existing literature for and experiences with UAE in symptomatic disease. The panel acknowledged that before the pursuit of a clinical trial, it would be necessary to first evaluate the imaging criteria for adenomyosis and correlate them with pathology and symptoms to establish a noninvasive imaging classification system. Second priority was given to the development of a quality of life questionnaire to assess patient outcomes following treatment. The third priority was the performance of a prospective clinical trial comparing UAE with medical therapy, which would help establish UAE in the treatment algorithm and societal guidelines for symptomatic adenomyosis.     

Diagnosis of lumbar spinal stenosis in adults: a metaanalysis of the accuracy of CT, MR, and myelography.

We undertook a literature synthesis of CT, MR, and myelographic studies to evaluate what is known about the diagnostic accuracy of these imaging tests for the diagnosis of lumbar spinal stenosis in adults without prior surgery. From 116 possibly relevant studies, we reviewed 14 articles that included cases of spinal stenosis with a reference standard other than the imaging tests of interest. Of the studies we reviewed, two involved only MR, nine only CT, and three used both; six studies included myelography. Rating categories of A, B, C, or D were assigned for the quality of research methods used to estimate diagnostic accuracy. All studies received either a C or D rating. Common methodologic problems were failure to assemble a representative cohort for study, small sample size, and failure to maintain independence between image readings and reference standards. Sensitivity ranged from 0.81 to 0.97 for MR, from 0.70 to 1.0 for CT, and from 0.67 to 0.78 myelography. Studies varied greatly in case selection, definition of test and disease categories, and geographic locale, so no pooled estimates could be derived. In asymptomatic patients, abnormal findings appeared on CT or MR in 4-28% of cases and were more common in the elderly. Published studies of the value of CT and MR for the diagnosis of lumbar stenosis lack methodologic rigor and do not permit strong conclusions about the relative diagnostic accuracies of these procedures. For the present, the choice between MR or CT depends on issues such as costs, reimbursements, access to equipment, skill of radiologists, and patient safety. Better studies will be needed to document claims for improvements in imaging accuracy as MR technologies evolve. These studies should emphasize larger sample sizes, more attention to research designs that avoid methodologic biases, and the contribution of imaging diagnoses to ultimate clinical outcome.     

Nuclear cardiac stress testing in the era of molecular medicine.

The objective of cardiac stress testing is to detect coronary artery disease (CAD) and to prevent future adverse events, such as myocardial infarction or death. The progression from electrocardiographically based stress testing to current SPECT and PET technologies has brought improvements in diagnostic efficacy and resolution. Myocardial perfusion imaging facilitates management of CAD in elective and acute settings by providing valuable diagnostic and prognostic information. Hybrid PET/CT and SPECT/CT systems impart complementary information of coronary anatomy and its physiologic significance on blood flow reserve. In the current era, diagnosis and treatment of cardiovascular disease is increasingly defined by underlying molecular and genomic aberrations rather than by clinical signs and symptoms alone. Nuclear imaging is uniquely primed to exploit the targeting of expressed cell-surface molecules and intracellular processes of cardiovascular disease and to foster the development of innovative therapeutic interventions in the future.     

Efficacy of CBCT for assessment of impacted mandibular third molars: a review – based on a hierarchical model of evidence

A radiographic examination of mandibular third molars is meant to support the surgeon in establishing a treatment plan. For years panoramic (PAN) imaging has been the first choice method; however, where an overprojection is observed between the third molar and the mandibular canal and when specific signs suggest a close contact between the molar and the canal, CBCT may be indicated. The present review provides an evaluation of the efficacy of CBCT for assessment of mandibular third molars using a six-tiered hierarchical model by Fryback and Thornbury in 1991. Levels 1–3 include studies on low evidence levels mainly regarding the technical capabilities of a radiographic method and the diagnostic accuracy of the related images. Levels 4–6 include studies on a higher level of evidence and assess the diagnostic impact of a radiographic method on the treatment of the patient in addition to the outcome for the patient and society including cost calculations. Only very few high-evidence studies on the efficacy of CBCT for radiographic examination of mandibular third molars exist and, in conclusion, periapical or PAN examination is sufficient in most cases before removal of mandibular third molars. However, CBCT may be suggested when one or more signs for a close contact between the tooth and the canal are present in the two-dimensional image—if it is believed that CBCT will change the treatment or the treatment outcome for the patient. Further research on high-evidence levels is needed.     

Temporomandibular joint diagnostics using CBCT

The present review will give an update on temporomandibular joint (TMJ) imaging using CBCT. It will focus on diagnostic accuracy and the value of CBCT compared with other imaging modalities for the evaluation of TMJs in different categories of patients; osteoarthritis (OA), juvenile OA, rheumatoid arthritis and related joint diseases, juvenile idiopathic arthritis and other intra-articular conditions. Finally, sections on other aspects of CBCT research related to the TMJ, clinical decision-making and concluding remarks are added. CBCT has emerged as a cost- and dose-effective imaging modality for the diagnostic assessment of a variety of TMJ conditions. The imaging modality has been found to be superior to conventional radiographical examinations as well as MRI in assessment of the TMJ. However, it should be emphasized that the diagnostic information obtained is limited to the morphology of the osseous joint components, cortical bone integrity and subcortical bone destruction/production. For evaluation of soft-tissue abnormalities, MRI is mandatory. There is an obvious need for research on the impact of CBCT examinations on patient outcome.     

Magnetic resonance imaging or arthrography for shoulder problems: a randomised study

Objective: Diagnostic technologies are often assessed merely by their accuracy, rather than by their impact on diagnosis and patient management. To this end the authors have undertaken a study to assess the diagnostic and therapeutic impact of magnetic resonance imaging (MRI) and arthrography of the shoulder for patients referred from a rheumatology clinic. Methods and patients: Patients referred from a rheumatology clinic with symptoms warranting imaging of the shoulder were randomised to either MRI or arthrography. Data on the clinician’s diagnostic confidence and management were recorded before and after imaging using questionnaires. Patients were followed-up at least 10 months after imaging to see how management plans evolved, and what proportion of patients required further imaging. Results: Fifty three shoulders underwent imaging over a year and entered into the study; 29 randomised to MRI and 24 to arthrography. Both MRI and arthrography had a similar beneficial diagnostic impact in terms of clinical diagnoses (refuted and retained) and new diagnoses established. MRI and arthrography had a similar therapeutic impact, although MRI was associated with a significant shift towards surgical intervention. Conclusion: MRI and arthrography a have similar diagnostic and therapeutic impact.