Assessment and non-clinical impact of medical devices.

Medical devices (MDs) cover a wide variety of products. They accompany changes in medical practice in step with technology innovations. Innovations in the field of MDs can improve the conditions of use of health technology and/or modify the organisation of care beyond the strict diagnostic or therapeutic benefit for the patients. However, these non purely clinical criteria seem to be only rarely documented or taken into account in the assessment of MDs during reimbursement decisions at national level or for formulary listing by hospitals even though multidimensional models for the assessment of health technologies have been developed that take into account the views of all stakeholders in the healthcare system In this article, after summarising the background concerning the assessment of health technologies in France, a definition of non-clinical criteria for the assessment of MDs is proposed and a decision tree for the assessment of MDs is described. Future lines of approach are proposed as a conclusion.

Scientific evaluation and pricing of medical devices and associated procedures in France.

Medical devices are many and various, ranging from tongue spatulas to implantable or invasive devices and imaging machines; their lifetimes are short, between 18 months and 5 years, due to incessant incremental innovation; and they are operator-dependent: in general, the clinical user performs a fitting procedure (hip implant or pacemaker), a therapeutic procedure using a non-implantable invasive device (arrhythmic site ablation probe, angioplasty balloon, extension spondyloplasty system, etc.) or follow-up of an active implanted device (long-term follow-up of an implanted cardiac defibrillator or of a deep brain stimulator in Parkinson's patients). A round-table held during the XXVIII(th) Giens Workshops meeting focused on the methodology of scientific evaluation of medical devices and the associated procedures with a view to their pricing and financing by the French National Health Insurance system. The working hypothesis was that the available data-set was sufficient for and compatible with scientific evaluation with clinical benefit. Post-registration studies, although contributing to the continuity of assessment, were not dealt with. Moreover, the focus was restricted to devices used in health establishments, where the association between devices and technical medical procedures is optimally representative. An update of the multiple regulatory protocols governing medical devices and procedures is provided. Issues more specifically related to procedures as such, to non-implantable devices and to innovative devices are then dealt with, and the proposals and discussion points raised at the round-table for each of these three areas are presented.

Place of patient-reported outcomes & experiences measurements (PROMS/PREMS) in the assessment and pricing of Health technologies in France.

In the context of health technologies assessment, patient-reported outcome measures (PROMs) have become assessment criteria that are expected by evaluation agencies along with the other usual clinical criteria. PROMs instruments measure all aspects of patient experience in connection with their health: symptoms, activities of daily living (physical function, sleep, etc.), various aspects of health-related quality of life (QoL), compliance, global impression of change in wellbeing. PROMs are useful both as 1) a primary or secondary efficacy endpoints, and 2) a tolerability criterion to supplement vigilance data reported by clinicians. Measurement of PROMs must be subject to methodological rigor that is identical to that of other assessment criteria measured by an observer. Scales must be validated, suitable for the objective, and where possible specific to a disease. In addition to standard measures of quality of life, PROMs are taken into consideration in the assessments performed by the HAS, even if their impact on the conclusions is difficult to isolate, as assessments are multifactorial and take into account all data available with regard to the medical context. The CEPS will indirectly take into account PROMs in the fixing of the price or tariff only if they have contributed to the award of the ASA/ASMR by the ad hoc committee of the HAS. The working group has formulated three recommendations which aim to further the implementation of patient-reported outcome measures: (1) Better information for all parties involved in a dossier for technology assessment, (2) Systematization of the collection of PROMs for evaluation of health products, (3) Improved quality of dossiers thanks to the use of relevant and validated tools.

[Epithelioid schwannoma of the colon. Report of two cases]. / Schwannome épithélioïde colique: étude anatomo-clinique de deux cas.

Schwannomas of the colon are rare tumors. Most of them are spindle cell tumors. The epithelioid variant is exceedingly rare with only 10 cases reported in the literature. We report two fortuitously discovered cases in 37 and 42-year-old women. The masses were located in the sigmoid and the right colon. They measured 2,5 and 3 cm in diameter. On microscopic examination, they were composed of sheets of uniform epithelioid cells without atypia or mitosis. One of them had a cuff of benign lymphoid hyperplasia. Immunohistochemical study showed positive staining of the tumor cells for S100 protein and some of them for glial fibrillary acidic protein. Some CD34-positive fibroblast-like cells were identified in the two tumors. There was no recurrence with a follow-up ranging from 6 to 24 months. Epithelioid schwannoma of the colon is a benign tumor of uncertain histogenesis which may be confused with more aggressive neoplasms.

Long-term prognostic value of detection of circulating colorectal cancer cells using CGM2 reverse transcriptase-polymerase chain reaction assay.

BACKGROUND: The criteria commonly used for prognosis of colorectal cancer remain histoprognostic and are based on primarily TNM classification. The lack of discrimination of purely histoprognostic criteria is evidenced by the development of different outcomes in similarly staged patients. The aim of this work was to study the long-term prognostic value of preoperative detection of circulating enterocytes in the blood of colorectal cancer patients using the CGM2 reverse transcriptase-polymerase chain reaction (RT-PCR) assay. METHODS: A nested RT-PCR with specific primers for CGM2 was used preoperatively to detect circulating enterocytes in 121 patients (64 men, 57 women; mean age, 70 years) with colorectal neoplasms. RESULTS: Circulating enterocytes were detected in 58/121 (48%) patients. The positivity rate was not correlated with American Joint Committee on Cancer (AJCC) staging (stage I, 11/28 (39%); stage II, 13/34 (38%); stage III, 15/23 (65%); stage IV, 17/32 (53%); sterilized (after radiotherapy, no residual neoplasm) 2/4 (50%); not significant [NS]), but circulating enterocytes were detected more frequently in patients with metastatic lymph nodes (60% vs 41%, P = .06). Overall 5-year survival rates (mean +/- SD) were 40 +/- 13% and 45 +/- 13% for patients without and with circulating enterocytes, respectively (P = NS). Similarly, recurrence-free survival rates were 71 +/- 4% versus 72 +/- 14% (P = NS). Using univariate analysis, AJCC stage (P < .0001) was correlated with survival. AJCC stage (P = .007) and obstructive neoplasms (P = .043) were correlated with recurrence-free survival. Using multivariate analysis, AJCC stage was correlated with survival and recurrence-free survival. CONCLUSIONS: Preoperative detection of circulating enterocytes using CGM2 RT-PCR assay provides no specific prognostic information and cannot be used as a decision criterion for adjuvant therapy.

Immunobead multiplex RT-PCR detection of carcinoembryonic genes expressing cells in the blood of colorectal cancer patients.

Circulating cell detection using reverse transcriptase-polymerase chain reaction (RT-PCR) techniques has been studied as a new prognostic factor in colorectal cancer patients. With the view of enhancing detection sensitivity, we developed a new multiplex RT-PCR assay for circulating cell detection based on the expression of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5; formerly CEA) and CEACAM7 (formerly CGM2). Between November 2002 and December 2003, 45 stage III-IV, 39 stage I-II colorectal cancer patients, 32 non-colorectal cancer patients and 41 healthy individuals were included. Positive selection using HEA-125 immunobeads was applied to blood samples before mRNA extraction, cDNA synthesis and a multiplex CEACAM5/CEACAM7 RT-PCR assay. For both CEACAM5 and CEACAM7, the limit of detection was found to be as low as 1 expressing cell in 10(6) nucleated blood cells. The multiplex RT-PCR assay was negative for the 41 healthy individuals and the 32 non-colorectal cancer patients. The test was positive in 53/84 (63%) of the colorectal cancer patients for CEACAM5 and/or CEACAM7, whereas 32/84 (38%) were positive for both markers. Colorectal cancer patients were positive for one of the two markers in 80% of cases (36/45) for stage III-IV patients (CEACAM5 73%, CEACAM7 51%) and in 44% of cases (17/39) for stage I-II patients. This multiplex RT-PCR assay with two markers proved to be more sensitive than use of a single marker in detecting circulating tumour cells. The discrepant expression of CEACAM5 and CEACAM7 may label circulating tumour cells that have different levels of differentiation and subsequent aggressive behaviour.

Decrease in left ventricular ejection time on digital arterial waveform during simulated hypovolemia in normal humans.

BACKGROUND: Left ventricular ejection time (LVET) measured in central arteries is modified during hypovolemia. We compared modifications of the pulse wave in a central artery (carotid) and in a peripheral artery (digital) during central hypovolemia induced by lower body negative pressure (LBNP) in conscious volunteers. METHODS: Hypovolemia was simulated with progressive LBNP (baseline, -10, -20, and -30 mm Hg) in nine young healthy volunteers. The carotid arterial pressure waveform was recorded using a Millar tonometric method. The digital pulse wave was measured with a volume-clamp method (Finapres) and the stroke volume with a thoracic impedance method (Biomed). RESULTS: Mean arterial pressure did not change during LBNP. Compared with baseline values, heart rate increased significantly at the -30 mm Hg level (68 +/- 13 beats/min vs. 59 +/- 11 beats/min), and stroke volume decreased as soon as -10 mm Hg was achieved (113 +/- 41 mL vs. 127 +/- 35 mL). Both carotid and digital LVET decreased significantly at the -10 mm Hg level (337 +/- 26 and 339 +/- 24 ms vs. 360 +/- 35 and 361 +/- 24 ms, respectively). CONCLUSION: Peripheral LVET could reflect variation of central LVET during LBNP and be a reliable noninvasive parameter for monitoring hypovolemia.