Differences in Evidentiary Requirements Between European Medicines Agency and European Health Technology Assessment of Oncology Drugs—Can Alignment Be Enhanced?

ObjectivesNational health technology assessments (HTAs) across Europe show differences in evidentiary requirements from assessments by the European Medicines Agency (EMA), affecting time to patient access for drugs after marketing authorization. This article analyzes the differences between EMA and HTA bodies’ evidentiary requirements for oncology drugs and provides recommendations on potential further alignment to minimize and optimally manage the remaining differences.MethodsInterviews were performed with representatives and drug assessment experts from EMA and HTA bodies to identify evidentiary requirements for several subdomains and collect recommendations for potentially more efficiently addressing differences. A comparative analysis of acceptability of the evidence by EMA and the HTA bodies and for potential further alignment between both authorities was conducted.ResultsAcceptability of available evidence was higher for EMA than HTA bodies. HTA bodies and EMA were aligned on evidentiary requirements in most cases. The subdomains showing notable differences concerned the acceptance of limitation of the target population and extrapolation of target populations, progression-free survival and (other) surrogate endpoints as outcomes, cross-over designs, short trial duration, and clinical relevance of the effect size. Recommendations for reducing or optimally managing differences included joint early dialogues, joint relative effectiveness assessments, and the use of managed entry agreements.ConclusionsDifferences between assessments of EMA and HTA bodies were identified in important areas of evidentiary requirements. Increased alignment between EMA and HTA bodies is suggested and recommendations for realization are discussed.     

An Evidence-Based Review of Total Body Irradiation

The purpose of this literature review is to investigate clinical treatment methods of total body irradiation within the context of a clinical department adopting a paediatric cohort with no existing technique. An extensive review of the literature was conducted using PubMed, Science Direct, Google Scholar, and Clinicians Knowledge Network. Articles were limited to nonhelical tomotherapy, nonparticle therapies, and those using hyperfractionated regimes. Total marrow irradiation was excluded because of national treatment and trial limitations. Of the numerous patient positioning methods present within the literature, the most comfortable and reproducible positioning methods for total body irradiation include both supine and the supine and/or prone combination. These positions increased stability and patient comfort during treatment, while also facilitating computed tomography data acquisition at the simulation stage. Ideally, dose calculations should be performed using a three-dimensional treatment planning system and quality assurance procedures that include in vivo dosimetry measurements. The available literature also suggests inhomogeneity correction factors and intensity modulation are superior to conventional open field techniques and should be implemented within developing protocols. Dynamic machine dose modulation is suggested to reduce department impact, removing the need for tissue compensators and accessory shielding devices, while providing significant improvements to treatment time and dose accuracy. Further long-term survival and intensity modulation studies are warranted, including direct comparisons of both dose modulation and treatment efficiency.     

Family Caregivers' Subjective Caregiving Burden,Quality of Life,and Depressive Symptoms Are Associated With Terminally Ill Cancer Patients' Distinct Patterns of Conjoint Symptom Distress and Functional Impairment in Their Last Six Months of Life

Context

Family caregivers constitute a critical component of the end-of-life care system with considerable cost to themselves. However, the joint association of terminally ill cancer patients' symptom distress and functional impairment with caregivers' subjective caregiving burden, quality of life (QOL), and depressive symptoms remains unknown.

Hand-assisted laparoscopic nephroureterectomy for upper urinary tract transitional cell carcinoma.

OBJECTIVE: We report our experience with hand-assisted laparoscopic nephroureterectomy (HALN) for upper urinary tract transitional cell carcinoma and compare our results with a contemporary series of open nephroureterectomy (ON) performed at our institution. METHODS: Between August 1996 and May 2003, 90 patients underwent nephroureterectomy for upper-tract transitional cell carcinoma (TCC). Thirty-eight patients underwent HALN, while 52 had an ON. End-points of comparison included operative time, estimated blood loss (EBL), intraoperative and postoperative complications, length of hospital stay, pathologic grade and stage of tumor, and tumor recurrence. RESULTS: The mean patient age was 72.3 and 70.6 years in the ON and HALN groups, respectively. Mean operative duration was 243 minutes (ON) and 244 minutes (HALN), with an EBL of 478mL in the open group versus 191 mL in the hand-assisted group (P<0.001). No intraoperative complications occurred, but postoperative complications occurred in 4% and 11% of the ON and HALN groups, respectively (P=0.21). The mean hospital duration was 7.1 days (ON) versus 4.6 days (HALN) (P<0.01). No difference existed in the pathologic grade or stage distribution of urothelial tumors between the 2 groups. The mean follow-up was 51.0 months in the ON group and 31.7 months in the HALN group. Recurrence of urothelial carcinoma occurred in 50% of patients who underwent ON and 40% treated by HALN (P=0.38) at a median interval of 9.1 and 7.7 months, respectively, after surgery. CONCLUSION: Hand-assisted laparoscopic nephroureterectomy is an effective modality for the treatment of upper urinary tract urothelial carcinoma. Patients benefited from less intraoperative blood loss and a shorter hospitalization with an equivalent intermediate-term oncologic outcome compared with that of the open approach.     

Approaches for end-of-life care in the field of gynecologic oncology: an exploratory study

We sought to explore the Society of Gynecologic Oncologists (SGO) members' opinions and decisions about end-of-life issues and incurable conditions. A survey was mailed to members of the SGO. Their responses were recorded on a Likert scale and entered into a database. The survey explored opinions, experiences, and decisions in managing terminally ill gynecologic oncology patients. Of 900 surveys, 327 were returned (response rate, 36%). Seventy-three percent were men, 89% were white, and 72% were of Christian denomination. Respondents believed that 97% of patients who are dying realize that they are dying but stated only 40% of these patients initiate conversations about end-of-life issues. In contrast, 92% of respondents stated that they initiate end-of-life discussions with patients. Ninety-two percent of respondents thought that the patients should be allowed to make end-of-life choices independently after the facts are given to them. However, 44% thought that it is important to influence the way information is presented, and 54% believe that the gynecologic oncologist (GO) controls the outcome of end-of-life discussions. Although the physicians' sex, race, religion, and age did not correlate with their treatment decisions, religion did correlate with less fear of death (P = 0.011) and less discomfort when talking with patients about death (P = 0.005). Fifty-four percent of respondents believed that the GO controls the outcome of end-of-life discussions, and 40% believe that their actions prolong the process of dying. Expanding our understanding of what motivates GOs to recommend continued treatment over palliation is important for preserving informed patient-motivated end-of-life decisions.     

妇科腹腔镜手术几种激光对兔子宫壁损伤的实验研究

为掌握妇科腹腔镜手术所应用的激光器的治疗剂量，对几种激光引起的兔子宫壁热损伤进行观察。实验研究证实：所有激光产生的损伤程度与所用的剂量呈正相关。术后４８ｈ与即刻损伤程度相比，半导体激光的损伤程度明显加深、加宽；但ＣＯ２激光和ＮｄＹＡＧ激光接触式光刀无显著变化。说明应用激光行妇科腹腔镜手术治疗时，所产生的损伤与应用的功率密度有关，为临床合理选用腹腔镜下的激光治疗提供依据     

高强度聚焦超声及其医学应用

HIFU技术的研究在国内外已掀起了热潮．到目前为止．HIFU技术已得到广泛的实验和临床支持。本文将对HIFU治疗设备的总体结构做一阐述．并讨论其在医学领域中的应用及发展方向。     

History of Pediatric Oncology

Pediatric oncology emerged as a subspecialty in the United States of America following the observations in 1948 of Farber and his associates of the benefits of chemotherapy for acute leukemia. The establishment of national cooperative chemotherapy groups furthered its development. More recently, the subspecialty has been recognized by the American Board of Pediatrics. Even more recently, training programs for the subspecialty have been given accreditation. Parallel to development of the specialty in the United States has been a similar evolution of pediatric oncology in Europe.     

Anal metastasis from carcinoma of the lung: Report of a case

We report herein the case of a 75-year-old man who developed anal canal metastasis from squamous cell carcinoma of the lung. Initially, he underwent a right middle and lower lobectomy combined with left atrial wall resection under cardiopulmonary bypass. He presented 3 months later with an anal polyp which had prolapsed and bled, for which he underwent a transanal polypectomy. Histologically, the polyp was classified as squamous cell carcinoma and considered to be a metastasis from the primary lung cancer. He is presently well with no signs of recurrence 9 months after his initial operation. To our knowledge, there has been no other case of anal metastasis from lung cancer ever reported.