The ABCs of the FDA: A Primer on the Role of the United States Food and Drug Administration in Medical Device Approvals and IR Research.

The role of the US Food and Drug Administration (FDA) in medical device regulation is important to device-driven specialties such as interventional radiology. Whether it is through industry-sponsored trials during the approval process for new devices or investigator-initiated research prospectively evaluating the role of existing devices for new or established procedures, interaction with the FDA is an integral part of performing significant research in interventional radiology. This article reviews the potential areas of interface between the FDA and interventional radiology, as understanding these areas is necessary to continue the innovation that is the hallmark of this specialty.

Characteristics of pivotal clinical trials of FDA-approved endovascular devices between 2000 and 2018: An interrupted time series analysis.

Background: The Food and Drug Administration (FDA) reviews safety, efficacy, and the quality of medical devices through its regulatory process. The FDA Safety and Innovation Act (FDASIA) of 2012 was aimed at accelerating the regulatory process for medical devices. Objectives: The purpose of our study was to (1) quantify characteristics of pivotal clinical trials (PCTs) supporting the premarket approval of endovascular medical devices and (2) analyze trends over the last two decades in light of the FDASIA. Methods: We surveyed the study designs of endovascular devices with PCTs from the US FDA pre-market approval medical devices database. The effect of FDASIA on key design parameters (e.g., randomization, masking, and number of enrolled patients) was estimated using an interrupted time series analysis (segmented regression). Results: We identified 117 devices between 2000-2018. FDASIA was associated with a decrease in double blinding (p < 0.0001) and a decrease in historical comparators (p < 0.0001). Discussion: Our results reveal an overall trend of decreased regulatory requirements as it relates to clinical trial characteristics, but a compensatory increased rate of post-approval across device classes. Furthermore, there was an emphasis on proving equivalence or non-inferiority rather than more use of active comparators in clinical trials. Medical device stakeholders, notably clinicians, must be aware of the shifting regulatory landscape in order to play an active role in promoting patient safety.

Review of venous anatomy for venographic interpretation in chronic cerebrospinal venous insufficiency.

Chronic cerebrospinal venous insufficiency (CCSVI) represents a recently described condition that may potentially contribute to the symptoms experienced by patients with multiple sclerosis. The evaluation of a prospective patient for CCSVI often involves an invasive evaluation with venography of the internal jugular and azygos veins. The purpose of this article is to review the normal anatomy of the internal jugular, vertebral, and azygos veins, as an understanding of these veins is necessary for appropriate interpretation of the venograms obtained to evaluate patients for CCSVI.

Percutaneous Biliary Endoscopy for Stones.

Intraductal biliary stones can result in significant acute and long-term complications. When patients' anatomy precludes more traditional management, the interventional radiologist may be called upon to provide well-established techniques for percutaneous biliary drainage and stone removal. This can be particularly challenging when the patient has excessively mobile, impacted, large or multiple stones. Percutaneous biliary endoscopy with adjunct interventional techniques can successfully treat these patients avoiding the patient dreaded "tube for life" scenario. Direct percutaneous visualization of the biliary tree can also diagnose and provide symptomatic relief for stone-mimicking pathologic conditions such as biliary tumors. This article will review the role, technique, and considerations for percutaneous biliary endoscopy and adjunct interventions in patients with isolated and complex, biliary stone disease and stone-mimicking pathologies.

Ureteral Interventions.

Interventional radiologists are commonly called upon to manage patients with benign and malignant ureteral pathologic conditions. Unfortunately, treatments for both cure and palliation can be fraught with problems causing patients to be undesirably maintained with lifelong catheters. This review describes outcomes for antegrade and retrograde therapeutic options and techniques for patients with most types of ureteral pathologic conditions that the interventional radiologist would encounter in practice.

Stone volume is best predictor of operative time required in retrograde intrarenal surgery for renal calculi: implications for surgical planning and quality improvement.

Retrograde intrarenal surgery (RIRS) is highly successful at eliminating renal stones of various sizes and compositions. As urologists are taking on more complex procedures using RIRS, this has led to an increase in operative (OR) times. Our objective was to determine the best predictor of OR time in patients undergoing RIRS. We retrospectively reviewed the records of patients undergoing unilateral RIRS for solitary stones over a 10 year time span. Stones were fragmented and actively extracted using a basket. Variables potentially affecting OR time such as patient age, sex, BMI, lower pole stone location, volume, Hounsfield units (HU), composition, ureteral access sheath (UAS) use, and pre-operative stenting were collected. Multivariable linear and stepwise regression was used to evaluate the predictors of OR time. There were 118 patients that met inclusion criteria. The median stone volume was 282.6 mm3 (IQR 150.7-644.7) and the mean OR time was 50 min (±25.9 SD). On univariate linear regression, stone volume had a moderate correlation with OR time (y = 0.022x + 38.2, r 2 = 0.363, p < 0.01). On multivariable stepwise regression, stone volume had the strongest impact on OR time, increasing time by 2.0 min for each 100 mm3 increase in stone volume (p < 0.001). UAS added 13.5 (SE 3.9, p = 0.001) minutes and renal lower pole location added 9 min (SE 4.3, p = 0.03) in each case they were used. Pre-operative stenting, HU, calcium oxalate stone composition, sex, and age had no significant effect on OR time. Amongst the main stone factors in RIRS, stone volume has the strongest impact on operative time. This can be used to predict the length of the procedure by roughly adding 2 min per 100 mm3 increase in stone volume.

Using Hounsfield unit measurement and urine parameters to predict uric acid stones.

OBJECTIVE: To determine the in vivo ability to predict uric acid stone composition by Hounsfield units (HU) with the addition of urine parameters. METHODS: We reviewed all consecutive stones sent for analysis during a 4-year period from our institution for patients with an in-house computed tomography (CT) scan within the prior 6 months and urinalysis within the prior week. CT scans were independently reviewed by a radiologist blinded to stone composition. RESULTS: Of the 507 patients with stones sent for analysis, 235 met the criteria for inclusion. Analysis showed 212 stones were predominantly calcium-based, and 22 were predominantly uric acid in composition. There was a significant difference between calcium stones and uric acid stones in mean HU (890 ± 20 vs 484 ± 44; P <.01) and urine pH (6.4 ± 0.8 vs 5.1 ± 0.2; P <.01). Receiver operating characteristic curve evaluation gave optimal predictive values of HU ≤494 (rounded to 500) and pH of ≤5.5 to predict uric acid stones. The combination of HU and pH criteria resulted in a sensitivity of 86% and a specificity of 98%, with a positive predictive value of 80%, which increased to 90% if we limited to stones >4 mm. CONCLUSION: Uric acid stones show a significant difference in HU and urine pH from calcium stones, and the use of both criteria is superior to either separately. For a stone >4 mm, a HU ≤500 and pH ≤5.5 has a positive predictive value of 90% for uric acid composition. Our prediction model gives a straightforward tool that can be easily measured to predict a uric acid stone.

Internet-based social networking and its role in the evolution of chronic cerebrospinal venous insufficiency.

The Internet is being seen as a growing resource for health-related information for a large number of patients. It is undeniable that its widespread presence has led to the growth of awareness that chronic cerebrospinal venous insufficiency (CCSVI) as an entity that may contribute to the symptoms experienced by patients with multiple sclerosis (MS). Social networking and file-sharing Web sites have brought patients with MS together from all over the world and have facilitated the distribution of personal experiences and information derived from medical research as it relates to CCSVI. As a result, there has been an accelerated growth in the number of patients seeking treatment for this syndrome in light of the possibility that it may improve their present condition. This article will review this phenomenon, the Internet-based resources available to MS patients seeking information about CCSVI, and the responsibilities of physicians as they participate in these online discussions.

Leiomyoma infarction after uterine artery embolization: a prospective randomized study comparing tris-acryl gelatin microspheres versus polyvinyl alcohol microspheres.

PURPOSE: To determine the degree of leiomyoma infarction after uterine artery embolization (UAE) performed with tris-acryl gelatin microspheres or polyvinyl alcohol (PVA) microspheres. MATERIALS AND METHODS: Patients determined to be candidates and scheduled for UAE were randomized prospectively to receive tris-acryl gelatin microspheres or PVA microspheres. The manufacturers' recommended technique was used for both products during the UAE procedures (including the recently described refined protocol for PVA microspheres). All patients underwent magnetic resonance (MR) imaging of the pelvis with contrast agent enhancement before and after the UAE procedure. On the postprocedural MR study, the degree of tumor infarction was assessed on postcontrast images. These findings were classified as follows: 100% infarction, 90%-99% infarction, 50%-89% infarction, and less than 50% infarction. Treatment failure was defined by enhancement of more than 10% of a patient's entire tumor burden. RESULTS: A total of 53 patients were enrolled in this study. Twenty-seven (mean age, 44.9 years) received PVA microspheres and 26 (mean age, 45.1 years) received tris-acryl gelatin microspheres. There were no significant differences in the preprocedural uterine volume, dominant tumor volume, location of dominant tumor, and presenting symptoms between populations. In the PVA microsphere group, treatment failure was seen in eight patients (29.6%). In the tris-acryl gelatin microsphere group, treatment failure was seen in one patient (3.8%), which was a significant difference between groups (P < or = .025). CONCLUSIONS: There was a significantly greater degree of tumor infarction in patients treated with tris-acryl gelatin microspheres during UAE than in patients who received PVA microspheres administered in accordance with a newly refined protocol. Given the known risk of recurrence in patients with persistent tumor enhancement after UAE, it is concluded that tris-acryl gelatin microspheres should be the preferred agent for UAE at this time.

Safety of limited supplemental iodinated contrast administration in azotemic patients undergoing CO2 angiography.

PURPOSE: To determine if limited doses of iodinated contrast significantly worsen the underlying renal insufficiency that had warranted the use of CO(2) for diagnostic angiography. METHODS: The records of 122 consecutive patients who had undergone CO(2) angiography for peripheral vascular disease at our institution over a 5-year period were reviewed. The volume and type of iodinated contrast and the volume of CO(2) administered were recorded. Serum creatinine measurements obtained before angiography and from 2 to 3 days after angiography were recorded. RESULTS: One hundred patients had pre-angiography and post-angiography creatinine levels available for analysis (51 CO(2) only, 49 CO(2) with iodinated contrast). The average pretreatment creatinine level was 2.8+/-1.5 mg/dL (range 1.8-6.6) for the CO(2) only group and 3.0+/-1.4 mg/dL (range 1.8-8.2) for the CO(2) plus iodinated contrast group (p=0.46). After angiography, the mean change in creatinine was +0.17+/-0.87 mg/dL for the CO(2) only group and +0.03+/-0.98 mg/dL in the CO(2) plus contrast group (p=0.27). Complications included 1 patient with a failing renal transplant who received iodinated contrast and ultimately required return to hemodialysis. A second patient had a transient 1-mg/dL rise of creatinine but did not require dialysis. CONCLUSIONS: This study supports the relative safety of CO(2) angiography with the limited used of iodinated contrast supplementation for diagnostic studies or interventions in azotemic patients with peripheral vascular disease.