bluuebunny/crossref_metadata_2025 huggingface dataset:
PP53 New Medical Device Law: Germany's Experience With Refund Restrictions
Authors: Müller Elvira , Neeser Kurt , Oelze Ilse-Barbara
Published: January 2019

Introduction:

Since 2005, new hospital examination and treatment methods (NUB) were reimbursed by hospital individual supplementary fees as long as they were not sufficiently covered by a DRG. In 2016, the NUB procedure was decisively changed by legal norm §137 h SGB.V to evaluate medical devices (MD) of high risk classes, particularly invasive, or new theoretical-scientific concepts versus treatment alternatives by the Federal Joint Committee (G-BA). Hospitals and manufacturers have to submit detailed information on the application of the MD and the scientific evidence to G-BA along with a NUB application. This assessment may lead to exclusion of the method from reimbursement by the statutory health insurance (SHI).

Methods:

The published MD consultation submissions, assessments and G-BA resolutions (to date) were analyzed regarding evaluation criteria, treatment potential and study obligation.

Results:

In 2017, nineteen procedures were reviewed by G-BA with respect to §137 h. Two ultra-controlled high-intensity focused ultrasound (HIFU) indications were regarded as having potential benefit but not sufficient evidence yet, thus respective studies have to be initiated. Three procedures were regarded as eligible according to §137 h but not yet evaluated. Six procedures (ultra-controlled HIFU in five indications, targeted lung denervation in chronic obstructive pulmonary disease) were rated as having no potential benefit, while eight procedures were regarded as not eligible according to §137 h.

Conclusions:

Initially put into place for high risk class and primarily invasive devices, consultations and assessments under §137 h show that there is some uncertainty around applicability criteria. The majority of those procedures which fell under the assessment law failed to be granted potential benefit as treatment alternative. Currently consultations are ongoing which could possibly lead to the exclusion of these methods from the performance spectrum of the SHI. Manufacturers should revise their study concepts in order to fulfill the specific demand for robust evidence.
PP67 Validity Of A Questionnaire Assessing Patient Medication Experiences
Authors: Kimman Merel , Wijsenbeek Marlies , Mostard Remy , Tak Nelleke , Rotteveel Adrienne , van Jaarsveld Xana , Storm Marjolein , Wijnsma Kioa , Gelens Marielle , van de Kar Nicole , Wetzels Jack , Dirksen Carmen
Published: January 2019

Introduction:

The Patient Experiences and Satisfaction with Medications (PESaM) questionnaire was recently developed. It consists of two disease-specific modules for evaluating drug treatment of idiopathic pulmonary fibrosis (IPF) and atypical hemolytic uremic syndrome (aHUS): (i) a generic module applicable to any medication, and (ii) a patient expectations module. This study assessed the validity and reliability of the generic module in a large sample of patients in the Netherlands.

Methods:

In 2017, the PESaM-questionnaire was sent out to IPF patients on pirfenidone or nintedanib, aHUS patients receiving eculizumab, and patients using advagraf after kidney transplantation. The generic module consists of 16 items related to the domains effectiveness, side-effects and ease of use, and assesses patient experiences regarding the impact of the medication on daily life and health, and satisfaction. Mean scores for each domain were calculated using a scoring algorithm. Content validity, construct validity, and reliability were assessed using recommended methods.

Results:

Patients (n=188) completed the generic module of whom 48 percent used pirfenidone, 36 percent nintedanib, 11 percent advagraf, and 5 percent eculizumab. Content validity was established. Expected associations between patient experiences, satisfaction, and quality of life (QoL) were generally confirmed, demonstrating construct validity. For example, a moderate to strong positive association was found between patient experiences and satisfaction with side-effects (correlation coefficient 0.625, p < 0.05), and low (positive) associations were found between patient experiences and QoL. Importantly, the PESaM-questionnaire was able to discriminate between patients using different medications. Intraclass correlation coefficients, for test-retest reliability, ranged between good and excellent for most domains.

Conclusions:

The PESaM questionnaire is a promising tool to provide scientific evidence regarding the patient's perspective in health technology assessments and reimbursement decision-making regarding (expensive) medications, but can also support shared decision-making and appropriate use of medication at the individual patient level. Further research will assess the questionnaire's responsiveness and generalizability of results to other patient populations.
PP96 Which Data For Dual Mobility Cups In Hip Arthroplasty?
Authors: Guerin Caroline , Olivier Cyril , Marguerite Camille , Pacull Aurélie , Collignon Corinne , Galmiche Hubert , Belorgey Chantal
Published: January 2019

Introduction:

The dual mobility concept was invented to prevent postoperative hip dislocation. It has been used for 40 years, but demonstrative data are limited and many designs are available. In France, many implants for hip arthroplasty are reimbursed by the national health insurance system through a generic description that corresponds to a class of products having the same indications and technical features (designs, coatings, types and systems of fixation). Dual mobility cups were one of them until 2017. The ministry decided to set up the assessment of each design of dual mobility cup, marketed in France for their reimbursement.

Methods:

Manufacturers of these devices submitted medico-technical application dossiers, with technical characteristics and clinical data, to the French National Authority for Health (HAS). HAS has assessed prospectively the actual benefit of these implants.

Results:

Sixteen companies marketing 42 kinds of dual mobility cups associated with 22, 28 or 32 mm femoral heads and cementless or cemented fixations have submitted dossiers. Their demands were argued on non-specific and specific clinical data. For few implants with non-specific clinical data, arguments to demonstrate the equivalence towards other implants were not accepted for reimbursement. For other implants, the specific data available were only low quality studies. No randomized controlled trials were identified. When the risk/benefit balance was acceptable, the implants were approved for reimbursement and HAS required post-launch data to assess the real-world safety of these implants (i.e. dislocation and long-term survival).

Conclusions:

All the dual mobility cups marketed in France have been assessed by the French health technology assessment authority. Most of them have been approved for reimbursement, despite of low level of evidence. The brand name inscription enables a specific follow up and the analysis of a post-approval study results in five years.
PP103 Early Decision Support In Innovative Procurement
Authors: Stome Linn Nathalie , Hengebol Kari , Kidholm Kristian , Kvaerner Kari
Published: January 2019

Introduction:

Procurement is one tool for the public sector to acquire need-based, innovative and effective solutions. To succeed in purchasing services that succeed in improving patients’ outcomes and optimize cost of care, the process must be accompanied with tools for early decisional support. Documenting the effects of healthcare innovation is therefore fundamental when dealing with prioritizing adequate technology. The aim of the present study was to review the literature to identify early assessment methodology applicable to innovative procurement processes.

Methods:

A scoping review was performed in January and February 2017 with the objective of selecting literature reporting on early assessment of health innovation. Methods for early assessment of health innovation were identified with the aim of investigating whether the methods change depending on where in the innovation process (development, introduction, and early diffusion) they are applied, and if the literature pointed to dominant methods. Next, critical elements of the innovative procurement process were identified, and methods relevant to the need-based phase of procurement were assessed.

Results:

In total 1064 articles met the search strategy. Based on predefined inclusion and exclusion criteria, thirty-nine articles were included in the study. When viewed in the light of innovative procurement, stakeholder insight was an important source of data in early assessment of potential benefits of health innovation. Such data can be applied in scenario analyses to provide necessary outcome overviews and to direct and accelerate the procurement process. Further, various simulation and analysis methods may be used in new ways to increase the impact of the scarce availability of data in early innovation phase.

Conclusions:

The present review identified tools for early decisional support that address risks and step-wise healthcare management support. Information based on the present review will also be addressed in Panel 26 “Accelerating Value Based Health Care with Innovative Procurement and Early Decisional Support”
PP109 Use Of Speech Recognition In Medical Reports: A Systematic Review
Authors: Poder Thomas , Déry Véronique , Fisette Jean-Francois
Published: January 2019

Introduction:

Speech recognition is increasingly used in medical reporting. The aim of this article is to identify in the literature the advantages and weaknesses of this technology, as well as barriers and facilitators to its implementation.

Methods:

A systematic review of systematic reviews has been conducted in PubMed, Scopus, Cochrane Library and Center for Reviews and Dissemination up to August 2017. The grey literature has also been consulted. The quality of systematic reviews has been assessed with the AMSTAR checklist. Inclusion criteria were to use speech recognition for medical reporting (front or back-end). A Survey has also been conducted in Quebec, Canada, to identify the dissemination of this technology in this province, as well as the factors of success or failure in its implementation.

Results:

Five systematic reviews were identified. These reviews indicated a high level of heterogeneity across studies. The quality of the studies reported was generally poor. Speech recognition is not as accurate as human transcription but can dramatically reduce the turnaround times for reporting. In front-end use, medical doctors need to spend more time for dictation and correction than with human transcription. With speech recognition, major errors can be up to three times more frequent. In back-end use, a potential increase in the productivity of transcriptionist is noted.

Conclusions:

Speech recognition offers some advantages for medical reporting, the main one being a reduction in turnaround times. However, these advantages are challenged by an increased burden for medical doctor and risks of additional errors in medical reports. It is also hard to identify for which medical specialties and which clinical activities the use of speech recognition will be the most beneficial.
PP116 Health Utilities And Neglected Conditions: A Chagas Disease Study
Authors: Miguel Sandro , Bagattini Ângela , Cruz Luciane , de Almeida Eros
Published: January 2019

Introduction:

Chagas disease (ChD), also known as American trypanosomiasis, is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. About 6 to 7 million people worldwide are estimated to be infected, most in Latin America. Health-related quality of life (HRQoL) and utility measures are still poorly employed for assessment of ChD lifetime impairments. Brazilian HRQoL published data showed that the cardiac subgroup of patients have worse scores than other ChD chronic groups. For the time being, utility scores are not available yet for the ChD population. The present study aims to assess quality of life (QoL), as utility scores, of patients with chronic Chagas Disease.

Methods:

This is a cross-sectional study. Data were collected from 183 outpatients with chronic ChD in a reference center in Brazil. Information pertaining to sociodemographics, clinical status, and quality of life were collected using self-administered questionnaires. Utilities were obtained by the European Quality of Life – 5 Dimensions (EQ-5D) questionnaire. Comparisons were made between clinical subtypes and population normative values. Continuous variables were compared using t-test or ANOVA, and categorical variables were compared using Chi-square test. Associations between QoL and patient characteristics stratified by demographics, clinical status were identified by linear regression models.

Results:

Most subjects were female (61 percent). The average age of men was 53.3 years and women 56.6. When analyzing the EQ-5D utility scores, it was observed that the results were lower for cardiac patients (0.610–95% CI 0.582–0.638) in comparison to indeterminate form patients (0.659–0.632–0.687). When comparing patients with the general population of the same age and sex, patients with ChD showed lower utility scores than normative values (0.624–95% CI 0.596–0.652).

Conclusions:

Chronic ChD causes a negative impact on quality of life, physical functioning, as well as psychosocial function, with the impairment becoming worse in cardiac patients.
PP122 A Quick Cost-Effectiveness Analysis Of Patent Foramen Ovale Closure In Korean Patients With Cryptogenic Stroke
Authors: Ahn Jeonghoon , Kim Eung Ju , Oh Kyungmi , Yoo Justin Seung-Ho , Koullick Maria
Published: January 2019

Introduction:

Patent foramen ovale (PFO) is an open hole between the right and left upper chambers of the heart. It may increase the risk of stroke, so closure of the hole is considered a secondary prevention in patients who have experienced cryptogenic stroke. Recent evidence has been published on the effectiveness of PFO closure, including a publicly funded prospective study on the effectiveness of PFO closure for preventing recurrent stroke or transient ischemic attack in selected Korean patients who have experienced cryptogenic stroke. The objective of this study was to examine the cost-effectiveness of PFO closure using this recent evidence.

Methods:

Available clinical data from the aforementioned Korean prospective study and other recent multicenter trials funded by public bodies were used. The cost data were obtained from the current Korean National Health Insurance fee schedule. Utility data were extracted from local research on stroke patients. A cost-effectiveness analysis, based on a 20-year Markov model, was conducted using these data to compare PFO closure plus antiplatelet therapy with oral anticoagulants alone.

Results:

The initial analysis showed that PFO plus antiplatelet therapy costs KRW 7.13 million (USD 6,547) more than oral anticoagulants alone but has a higher utility of 1.3 quality-adjusted life-years (QALYs) per patient, which corresponds to an incremental cost-effectiveness ratio (ICER) of KRW 5.6 million (USD 5,142) per QALY. The implicit Korean ICER threshold is KRW 25 million (USD 22,955) for non-cancer drugs, so it seems that PFO plus antiplatelet therapy is cost effective in the Korean setting.

Conclusions:

Since this study used some transition probabilities from foreign sources, the results may not be completely transferable to the Korean setting. However, this is the best available evidence so far in Korea for the economic evaluation of the PFO closure procedure. Therefore, use of PFO closure in carefully selected patients with a history of cryptogenic stroke may benefit the public payer in Korea.
PP124 Health Technology Assessment And Feedback For Healthy Workplace Culture In Malaria Care In Low And Middle Income Countries
Authors: Okwen Patrick , Cheabum Raphael , Che Etienne , Mbunu Joy Ngwemsi , Nkangu Miriam
Published: January 2019

Introduction:

Malaria is a leading cause of mortality and morbidity in children under five in low and middle income countries (LMICs). Management of malaria in children under five years of age is challenging. One challenge faced by clinical practice in LMICs is lack of evidence to guide practice. This challenge is further compounded by different training backgrounds of team members. In the management of malaria in Cameroon, conflicts usually arise between clinicians, lab technicians and pharmacists resulting in over diagnosis and treatment of malaria. The patient's view is usually not considered. This leads to over diagnosis and over prescriptions for malaria in children under five years of age.

Methods:

We used the Joanna Briggs Institute (JBI) approach of getting research into practice to organize stakeholder meetings, assess existing evidence in malaria care, develop evidence criteria for management based on levels of evidence, assess the gamut of care for malaria, provide feedback to clinicians and re-assess practice. We used the JBI practical application of clinical evidence system (PACES) and getting research into practice (GRiP) evidence implementation tools in the process to facilitate teamwork, collaboration on evidence and provide feedback.

Results:

A collaborative approach to assessments and feedback including all healthcare stakeholders significantly improved workplace culture of evidence-based care and staff-to-staff relationships as well as staff-to-patient relationships. Over a period of twelve months, we reported eighty-four percent fewer conflicts between staff and ninety-eight percent fewer conflicts between staff and patients. For malaria management, overall criteria showed a thirty-one percent improvement in compliance with best practice recommendations with evidence levels of Grade 1.

Conclusions:

The project demonstrated that local leadership and evidence-based care can significantly improve practice in resource limited settings.
PP135 Cost-Effectiveness Of Cryoballoon Ablation In China: Real-World Results
Authors: Ming Jian , Sun Hui , Wang Gongru , Wei Yan , Chen Yingyao , Pong Raymond
Published: January 2019

Introduction:

Paroxysmal atrial fibrillation (PAF) represents a significant economic burden to the healthcare system. Catheter ablation is a commonly adopted treatments for PAF, and cryoballoon ablation (CBA) has been recently proven to be as effective as radiofrequency ablation (RFA). This study aims to evaluate the cost-effectiveness of CBA versus RFA in patients with drug-refractory PAF in China.

Methods:

A Markov model was developed to study the effects and the costs of CBA versus RFA. Cost and probability inputs data were obtained mainly from a real-world study of 85 CBA and 284 RFA patients treated in a tertiary hospital between July 2014 and July 2016. Propensity score matching was used to overcome retrospective bias, resulting in including 75 patients in each group. Input data gaps were closed with literature review and advisory board. A simulation was carried out for 14 cycles/years, and a discount rate of 3 percent was used. Then, a probabilistic sensitivity analysis was carried out with Monte Carlo approach.

Results:

In the base case scenario, the cumulative costs incurred by the CBA and RFA groups were CNY 132,222 (USD 20,767) and CNY 147,304 (USD 23,136), respectively. Over the 14-year period, the quality-adjusted life years (QALYs) gained by the CBA group was 7.85 versus 7.71 in the RFA group. The incremental cost-effectiveness ratio for CBA versus RFA was thus CNY 107,729 (USD 16,920)/QALY. Model results were most sensitive to the cost incurred during the first hospitalization, recurrence rate, and relative utility weights. The probability of CBA being cost-effective for willingness to pay thresholds of per capita GDP in China was estimated to be 99 percent.

Conclusions:

Compared with RFA, CBA is a cost-saving treatment providing increased QALYs. It represents good value for money for patients with drug-refractory PAF in China. However, further evidence needs to be generated from larger-scale studies in China.
PP138 Cost-Effectiveness Analysis Of Influenza A (H1N1) Chemoprophylaxis
Authors: Vecoso Luisa , Silva Marcus , Silva Everton , Resende Mariangela , Galvao Tais
Published: January 2019

Introduction:

Influenza A (H1N1) virus is the most relevant virus in death by flu complications. Oseltamivir and zanamivir are used for influenza prophylaxis in epidemics. We aimed to evaluate the efficacy of chemoprophylaxis for influenza A (H1N1) for the Brazilian health care system.

Methods:

We systematically searched the literature to identify efficacy results. Costs assessed from the system perspective were obtained from official Brazilian Ministry of Health systems, and completed from medical care at a university hospital of Campinas, Sao Paulo. Model outcomes were quality-adjusted life years (QALY) with willingness to pay BRL 30,000 (USD 8,212)/QALY and prevention of H1N1. A decision-tree model was used to calculate the incremental cost-effectiveness ratios for prophylaxis, compared to no prophylaxis. Deterministic and probabilistic sensitivity analyses were used to test robustness of the model.

Results:

Prophylaxis had 70 percent adherence to treatment, 9 percent adverse events, effectiveness in avoiding H1N1 (relative risk = 0.43; 95% confidence interval: 0.33, 0.57); no evidence of prophylaxis efficacy for complication, hospitalization and death was found. Both scenarios had 14 percent H1N1 attack rate, 67 percent of ambulatorial consult, 43 percent of inpatient care, 14 percent of deaths in hospital, 23 percent of intensive care where death was 40 percent. Utility was 0.50 during H1N1 infection, 0.23 with hospitalization, 0.195 less with adverse events, 0 for deaths and 0.885 for healthy. Cost was BRL39 (USD 11) for chemoprophylaxis; BRL 12 (USD 4) for outpatient care; BRL 5,728 (USD 1,568) for hospital admission; BRL 19,217 (USD 5,260) for intensive care; and BRL 292 (USD 80) for adverse events. Incremental cost of prophylaxis was BRL 40 (USD 11) and utility increased 0.004, which mean saving of BRL 2,921 (USD 780)/QALY. Prophylaxis saves BRL 338 (USD 92) per H1N1 case avoided. Univariate and probabilistic sensitivity analysis assure the robustness of results, with 43 percent probability of being of lower cost and higher effectiveness.

Conclusions:

Prophylaxis is cost-effective from the health care system perspective using utility and avoided H1N1 cases outcomes.
PP151 Comparison Of Patients Undergoing New Technology For Prostate Cancer
Authors: Silva Deyvid , Lazarini Letícia , Aline Araujo , Trindade Evelinda , Becker Otavio , Nishio Elizabeth
Published: January 2019

Introduction:

Prostate neoplasia affects more than one million people worldwide. Surgical treatments have evolved from open or video prostatectomy, up to the High Intensity Focused Ultrasound (HIFU) technique. HIFU studies cite less costs and better quality of life during the first year of follow-up. The objective of this study is to describe a consecutive series of eligible patients, with Gleason score 6 and 7, and compare resources used along those three treatment techniques.

Methods:

A comparative and retrospective study was conducted during the first 2017 semester, at Hospital de Transplantes de São Paulo, São Paulo city, Brazil. Consecutive eligible patients were matched by age, disease stage and profile and Gleason score 6 or 7. Resources used were assessed through medical records review and in- and out-patient visit interviews.

Results:

A total of 152 patients were followed: 50 underwent open surgery prostatectomy, 50 underwent video prostatectomy and 52 underwent HIFU. Mean age did not differ between groups (66.6, 64.1 and 65.6 years, respectively). All patients were followed for at least three months. The average operating room time was 4.7, 4.1 and 2.3 hours, and the average anesthetic recovery time was 2.0, 1.9 and 2.0 hours, respectively. Average inpatient length of stay was 2.5, 2.7 and 1.5 days, respectively. Postoperatively, nine (18 percent) open surgery patients, and 14 (28 percent) video-prostatectomy patients required an average of one full day of intensive care, compared to only one (2 percent) HIFU patient. During follow-up, the same effectiveness was observed between the groups, none required re-intervention. Thus, considering the 50 percent economy in hours of operating room and of days of hospital stay, as well as 10 times less use of intensive care unit days when the HIFU technique was compared to conventional surgeries, it is estimated the HIFU program allowed 30 percent cost savings.

Conclusions:

The HIFU program presented effectiveness and savings. The hospital can increase access to care for prostate neoplasia patients.
PP158 The Art Of Collaboration In Guideline Development
Authors: Moga Carmen , Scott Ann
Published: January 2019

Introduction:

Developing clinical practice guidelines (CPGs) is a collaborative, multi-stakeholder enterprise. Over the last 13 years, health technology assessment (HTA) researchers from the Institute of Health Economics (IHE) partnered in a unique manner with provincial clinicians and stakeholders to develop and update CPGs using an innovative adaptation method. The complexities, intricacies, and attributes for success are presented, with emphasis on the role played by HTA resources.

Methods:

A governance structure (Advisory Committee, Steering Committee, Guideline Development Group) was designed to provide adequate oversight and quick, effective decision making, facilitate progress of the activities, and provide a mechanism for involving a wide variety of participants in the guideline development processes—stakeholders who represent policy, multidisciplinary care practice, knowledge translation, and research.

Results:

The HTA researchers served various functions and played multiple translation roles in the guideline development process: acting as a hub for connecting researchers with government to address relevant policy questions; liaising with committees to translate clinical queries into searchable questions for information specialists; preparing background documents and compiling discussion materials to expedite review by committees; connecting committees with external stakeholders such as the provincial CPG program; and bringing lay advisors into the final review process. Elements for success included effective communication, development and use of consistent methods, reliance on the highest quality of research evidence, willingness to contribute and share expertise, awareness of other initiatives and projects, transparency and openness, efficiency, flexibility, respect, enthusiasm, commitment, and patience.

Conclusions:

The development of CPGs requires the establishment of sophisticated multi-stakeholder collaboration and time. HTA agencies are well positioned to be an effective translation hub connecting the various stakeholders by virtue of their inherent ability to communicate in the language of policy makers, clinicians, and patients, so that all participants understand enough to add their voice to the process.
PD05 Influence Of Economic Data In The Incorporation Of Medicines In Brazil
Authors: Santos André , Ribeiro André , Ruas Cristina
Published: January 2019

Introduction:

Since 2011, the process of incorporation of technologies into the Brazilian public health system (SUS) has been assisted by the National Commission for the Incorporation of Technologies in SUS (Conitec). The present work collected data of effectiveness, safety, cost-effectiveness, budget impact and other criteria from Conitec's reports to determine the influence of economic evaluations on issued recommendations.

Methods:

Data was collected from drug recommendation reports published by Conitec between 2012 and 2016 and organized in a Microsoft Excel® spreadsheet. The association of the incremental cost-effectiveness ratio (ICER) and the chance of incorporation was assessed through a binary logistic regression in R®.

Results:

Two hundred and sixty-six reports were issued by Conitec between 2012 and 2016. Data were collected from 169 reports evaluating requisitions of incorporation of new medicines. Of these, there were ninety-nine which recommended the incorporation. The most common ATC classes analyzed were immunosuppressants (34 drugs), other antineoplastic agents (16 drugs) and direct-acting antivirals (15 drugs). Of the seventy negative recommendations, thirty-five were due to cost-effectiveness, thirty-one due to efficacy, twenty-nine due to safety, forty due to the budget impact, and thirty-two due to other reasons. In general, the reports were considered to be of poor quality. Only 21.9 percent of the reports had ICERs. The binary logistic regression analysis did not present a statistically significant difference for the influence of the ICER on the recommendation decision with outcomes reported in life years gained (OR = 0.9999732; 95% Confidence Interval [CI] = 0.9999304 to 1.000016) or quality-adjusted life years (OR = 0.9999789; 95% CI = 0.9999321 to 1.000026).

Conclusions:

Economic evaluations appear to be a secondary criterion for Conitec's recommendations. Despite this, they are commonly used to justify non-incorporation of drugs into the public system.
PD20 ‘Where's Waldo?’ Incorporating Patient Aspects Into Rapid Reviews
Authors: Thompson Lorna , Harbour Jenny , Macpherson Karen
Published: January 2019

Introduction:

Patient and social aspects form a key domain within health technology assessments (HTAs) but are less well established in rapid HTA. Patient aspects can add value to HTAs by aiding in interpretation of variations in intervention effectiveness or providing context on the impact of interventions on patients’ lives. This poster describes initial experience of incorporating patient aspects into a rapid HTA for the Scottish National Health Service.

Methods:

A rapid review explored using qualitative literature to understand patient issues relating to transoral robotic surgery (TORS) for head and neck cancer. Literature searches identified qualitative studies or systematic reviews of qualitative studies using two search filters: one for patient perspectives and another for qualitative study designs.

Results:

No qualitative literature specific to the exact question posed in the HTA was identified. Instead the project focused on patient experiences of alternative treatments (radiotherapy or open surgery) and identifying patient-important outcomes, such as speech function or lack of facial disfigurement. Pragmatic decisions on study selection were required in the TORS review due to the large volume of literature identified: we only included the most recent studies and limited our selection to patients with specific forms of head and neck cancer. Selecting studies from a large volume of literature may be an issue for future rapid HTAs attempting to incorporate qualitative evidence. The qualitative studies were summarised and used to inform advice issued to NHSScotland by the Scottish Health Technologies Group (SHTG).

Conclusions:

Patient aspects can be incorporated into rapid HTAs using systematic and pragmatic approaches to identifying and summarizing qualitative literature. Future rapid HTAs by SHTG may include syntheses of qualitative studies rather than summaries. Patient submissions are also being piloted as a method of collating patient experiences.
PD24 Data Collection By Patient Groups To Provide Patient Input
Authors: Berglas Sarah , Rader Tamara , Mai Helen
Published: January 2019

Introduction:

The Canadian Agency for Drugs and Technologies in Health (CADTH) Common Drug Review and pan-Canadian Oncology Drug Review programs incorporate perspectives and experiences from patients and family members who might be affected by the resulting funding recommendation. Perspectives are provided by patient groups who use different approaches to gather patient input.

Methods:

We analyzed a random sample of ninety-three patient input submissions, drawn from a sampling frame of 532 submissions given to CADTH between June 2010 and June 2016. We looked at how groups described their information gathering methods in the original submissions or the published Clinical Guidance Reports.

Results:

Approaches were categorized according to whether they involved primary (n = 86) or secondary data collection (n = 130) and further sub categorized according to how data was collected. Primary data included: personal experiences, as described by the submission's author (n = 16); surveys conducted specifically for the submission (n=34); and new interviews of patients and family members on disease and drug experiences (n = 36). Half (forty-seven of ninety-three) of the patient input submissions included experiences of one or more patients who had received the drug under review. Secondary data included: published literature (n = 31); existing surveys (n = 27); past conversations with patients and family members (n = 36); experiences of patient group staff interacting with patients and family members (n = 19); and advice from clinical experts (n = 17). Many patient input submissions (sixty-eight out of ninety-three) reported multiple approaches to collect data. Use of two approaches was most common (thirty-seven out of ninety-three) with five or six approaches used in three of ninety-three submissions.

Conclusions:

Despite resource and timing challenges, many patient groups gather primary data to share with CADTH and find individuals with experience of the drug under review.
PD44 Multi-Comparator Incremental Cost-Effectiveness Ratio: A New Framework For Cost-Effectiveness Analysis
Authors: Lucherini Stefano , Hughes Robert , Okhuoya Paul
Published: January 2019

Introduction:

Current practice in cost-effectiveness analysis (CEA) involves the estimation of the incremental cost-effectiveness ratio (ICER) between a new intervention and one alternative comparator reflecting the standard of care. As this focuses on pairwise comparisons, rather than considering the whole range of available alternatives at any given time, this method fails to capture the full impact of bringing the new intervention to market.

Methods:

A multi-comparator ICER (MC-ICER) evaluating the impact of the new technology on patients treated with all comparators used in clinical practice, rather than a theoretical ‘second-best’ alternative only, was estimated. This can be achieved by weighting the incremental costs and benefits for each comparator by its change in market share to generate an MC-ICER. This is shown using a stylized example with three comparators.

Results:

The traditional ICER against the second-best alternative was USD 200,000 per QALY, while the estimated multi-comparator ICER is USD 133,548 per QALY, corresponding to a 33 percent decrease. This reflects the fact that patients who switch to the new intervention are not only those who had been previously treated with one particular comparator, as is assumed in a traditional CEA. The difference between the traditional ICER and the MC-ICER depends on how the new intervention impacts on the uptake of each comparator.

Conclusions:

Results show that, when comparator selection was made excluding dominated and extendedly-dominated alternatives, the MC-ICER, produced using the method described above, is lower than the traditional ICER comparing the new intervention to the second-best comparator. This captures the fact that patients may switch to the new intervention not only from the second-best comparator, but from the whole range of alternative treatments. Such patient movements determine the real impact, or opportunity cost, of the new intervention on the healthcare system and, therefore, should be captured in CEA alongside traditional one-way ICERs.
VP21 Factors Associated With Recommendations On Drugs For Rare Diseases
Authors: Nagase Fernanda Inagaki , Sun Jian , Stafinski Tania , Menon Devidas
Published: January 2019

Introduction:

In Canada, reimbursement recommendations on drugs for common and rare indications (for example, orphan drugs) are made through the pan-Canadian Oncology Drug Review (pCODR) and the Common Drug Review (CDR). However, some stakeholders have called for a separate mechanism for orphan drugs, arguing that existing processes place too much weight on their high price tags. The purpose of this study was to examine factors associated with positive recommendations on drugs for rare diseases.

Methods:

Information was extracted from CDR and pCODR recommendations on drugs for diseases (prevalence of less than 1 in 2,000) up to April 2018. Univariate and multivariate logistic regression models were applied to explore the influence of the following variables on recommendations: year; prevalence; clinical safety and effectiveness (safety, quality of life, symptoms, surrogate outcomes, and survival); quality of evidence (availability of comparative data, external validity, and bias); unmet need; treatment cost; and incremental cost-effective ratio (ICER). Two-way interactions were also tested.

Results:

Of 128 recommendations, fifty-four (77 percent) and forty (69 percent) were positive for cancer and non-cancer indications, respectively. For cancer indications, all submissions reporting meaningful improvements in surrogate, quality of life, and survival outcomes were significantly more likely to have a positive recommendation. Submissions showing a lack of external validity were significantly less likely to receive a positive recommendation. For non-cancer indications, more recent submissions and those presenting no safety issues were associated with positive recommendations. Prevalence, treatment cost, and ICER were not determinants of positive or negative recommendations.

Conclusions:

For both cancer and non-cancer orphan drugs, impact on clinical safety and effectiveness, rather than cost, appears to be a key factor in the formulation of recommendations.
FDA-approved drugs for multiple sclerosis have no efficacy or disability data in non-Caucasian patients
Authors: Avasarala Jagannadha
Published: January 2019

Pharmacotherapy of multiple sclerosis (MS) is evolving rapidly. Despite impressive gains over the past 2 decades in the approval of multiple drugs for MS, lack of recruitment of minorities with MS in phase 3 clinical studies is a persistent concern and skews efficacy and disability data.
Compact polarimetry for automotive applications
Authors: Erhart Christian , Lutz Steffen , Mutschler Marc A. , Scharf Philipp A. , Walter Thomas , Mantz Hubert , Weigel Robert
Published: January 2019

Though compact polarimetric approaches have been developed and applied in space and geo researching systems they have not been taken into consideration in automotive applications, yet. A sensor system has been designed to conduct polarimetric measurements in the 77 GHz frequency band, which is permitted for automotive usage. This system is able to transceive linearly as well as circularly polarized electromagnetic continuous waves. Depending on the case of application, the frequency output can be set statically or modulated over time within adjustable parameters. Hence, a variety of compact polarimetric modes can be performed and compared with full polarimetric approaches. Two compact polarimetric modes, dual-circular polarimetric mode, and circular-transmit-linear-receive, will be introduced and applied in this contribution. Their operability in this frequency range will be investigated after the microstrip antennas as well as the beam focusing dielectrical lense are characterized. Finally, results of a realistical measurement set-up will confirm the practicability of compact polarimetric approaches for double bounce recognition.
Solar Wind Directional Change Triggering Flapping Motions of the Current Sheet: MMS Observations
Authors: Wang G. Q. , Zhang T. L. , Wu M. Y. , Schmid D. , Cao J. B. , Volwerk M.
Published: January 2019

We report on a flapping motion event near the substorm onset on 17 June 2017 using Magnetospheric Multiscale (MMS) mission data. A strong current density with a maximum value of ~190 nA/m2 is observed during the flapping. The north‐to‐south (south‐to‐north) crossing of the neutral sheet corresponds to an increase (a decrease) of the ZGSM component of the solar wind VZ, SW. The periods (~8 min) of the flapping and variations of VZ, SW are almost equal. In addition, dVZ, SW/dt and dBX/dt observed by MMS exhibit a strong negative correlation. These observations suggest that the flapping motions are triggered by the solar wind directional change via creating a motion of the current sheet in the north‐south direction. The pressure difference between the northern and southern lobes caused by the solar wind is expected to be a possible contribution to the formation of the flapping.
Scalable En Echelon Shear‐Fracture Aperture‐Roughness Mechanism: Theory, Validation, and Implications
Authors: Frash Luke P. , Carey J. William , Welch Nathan J.
Published: January 2019

Shear fractures can facilitate fluid conductivity through rock. Aperture and roughness are controlling characteristics for a fracture's fluid conductivity. Inspired by en echelon fractures, we develop a shear “fracturelet” model that predicts anisotropic aperture with respect to the direction of shearing, rougher (nonplanar) rather than smoother (planar) fractures, and the bounds of this roughness for a coalesced fracture. This tendency for rougher fracture creation is validated by in situ X‐ray images and fluid conductivity measurements from triaxial direct shear experiments on anhydrite and shale. These experiments were conducted at confining stresses from 4 to 30 MPa and shear displacement magnitudes from 0 to 2 mm on initially intact rock specimens. Hydraulic, dilatational, and local fracture apertures were measured in the experiments. Apertures exhibited strong anisotropy with more conductive flow paths forming perpendicular to the direction of shearing. Local and dilatational aperture were found to be positively correlated with increasing shear displacement but hydraulic aperture was found to vary significantly, always having values smaller than the other aperture measures at factors ranging from 0.6 to 0.0. An implication of these results is that shear fractures have a mechanism for simultaneously exhibiting very low fluid conductivity and high fluid storage volume.
Impacts of Precipitation on Ecosystem Carbon Fluxes in Desert‐Grasslands in Inner Mongolia, China
Authors: Zhang Rui , Zhao Xueyong , Zuo Xiaoan , Qu Hao , Degen A. Allan , Luo Yayong , Ma Xujun , Chen Min , Liu Liangxu , Chen Juanli
Published: January 2019

The frequency and amount of precipitation exert profound impacts on plants and the soil subsystem in dryland ecosystems. To quantitatively assess the effect of precipitation on ecosystem carbon fluxes during the growing season, a field experiment was carried out in a native desert‐grassland ecosystem in Inner Mongolia to determine the dynamics of ecosystem carbon fluxes along a precipitation gradient (−60%, −40%, −20%, CK, +20%, +40%, and +60%; CK is natural precipitation). The net ecosystem productivity (NEP) and gross ecosystem productivity (GEP) exhibited a single peak, whereas ecosystem respiration (Reco) exhibited a bimodal peak across all precipitation treatments. Reco reached its highest value at the beginning of August, whereas NEP and GEP reached their highest values at the end of August. Mean values of carbon fluxes increased with an increase in precipitation (from NEP: 0.06 μmol · m−2 · s−1, Reco: 0.37 μmol · m−2 · s−1, GEP: 0.42 μmol · m−2 · s−1 at −60% to NEP: 1.25 μmol · m−2 · s−1, Reco: 0.93 μmol · m−2 · s−1, and GEP: 2.18 μmol · m−2 · s−1 at +60%). Increased precipitation stimulated GEP more so than Reco during the growing season, resulting in an enhanced NEP, and decreased precipitation reduced GEP more so than Reco, leading to a reduced NEP. We concluded that the carbon sequestration capacity was enhanced by increased precipitation in the desert‐grassland ecosystem.
Variations of Lake Ice Phenology on the Tibetan Plateau From 2001 to 2017 Based on MODIS Data
Authors: Cai Yu , Ke Chang‐Qing , Li Xingong , Zhang Guoqing , Duan Zheng , Lee Hoonyol
Published: January 2019

Lake ice is a robust indicator of climate change. The availability of information contained in Moderate Resolution Imaging Spectroradiometer daily snow products from 2000 to 2017 could be greatly improved after cloud removal by gap filling. Thresholds based on open water pixel numbers are used to extract the freezeup start and breakup end dates for 58 lakes on the Tibetan Plateau (TP); 18 lakes are also selected to extract the freezeup end and breakup start dates. The lake ice durations are further calculated based on freezeup and breakup dates. Lakes on the TP begin to freezeup in late October and all the lakes start the ice cover period in mid‐January of the following year. In late March, some lakes begin to break up, and all the lakes end the ice cover period in early July. Generally, the lakes in the northern Inner‐TP have earlier freezeup dates and later breakup dates (i.e., longer ice cover durations) than those in the southern Inner‐TP. Over 17 years, the mean ice cover duration of 58 lakes is 157.78 days, 18 (31%) lakes have a mean extending rate of 1.11 day/year, and 40 (69%) lakes have a mean shortening rate of 0.80 day/year. Geographical location and climate conditions determine the spatial heterogeneity of the lake ice phenology, especially the ones of breakup dates, while the physico‐chemical characteristics mainly affect the freezeup dates of the lake ice in this study. Ice cover duration is affected by both climatic and lake specific physico‐chemical factors, which can reflect the climatic and environmental change for lakes on the TP.
The mitochondrial type IB topoisomerase drives mitochondrial translation and carcinogenesis
Authors: Baechler S. A. , Factor V. M. , Dalla Rosa I. , Ravji A. , Becker D. , Khiati S. , Miller Jenkins L. M. , Lang M. , Sourbier C. , Michaels S. A. , Neckers L. M. , Zhang H. L. , Spinazzola A. , Huang S. N. , Marquardt J. U. , Pommier Y.
Published: January 2019

Mitochondrial topoisomerase IB (TOP1MT) is a nuclear-encoded topoisomerase, exclusively localized to mitochondria, which resolves topological stress generated during mtDNA replication and transcription. Here, we report that TOP1MT is overexpressed in cancer tissues and demonstrate that TOP1MT deficiency attenuates tumor growth in human and mouse models of colon and liver cancer. Due to their mitochondrial dysfunction, TOP1MT-KO cells become addicted to glycolysis, which limits synthetic building blocks and energy supply required for the proliferation of cancer cells in a nutrient-deprived tumor microenvironment. Mechanistically, we show that TOP1MT associates with mitoribosomal subunits, ensuring optimal mitochondrial translation and assembly of oxidative phosphorylation complexes that are critical for sustaining tumor growth. The TOP1MT genomic signature profile, based on Top1mt-KO liver cancers, is correlated with enhanced survival of hepatocellular carcinoma patients. Our results highlight the importance of TOP1MT for tumor development, providing a potential rationale to develop TOP1MT-targeted drugs as anticancer therapies.
A tumor-specific endogenous repetitive element is induced by herpesviruses
Authors: Nogalski Maciej T. , Solovyov Alexander , Kulkarni Anupriya S. , Desai Niyati , Oberstein Adam , Levine Arnold J. , Ting David T. , Shenk Thomas , Greenbaum Benjamin D.
Published: January 2019

Tandem satellite repeats account for 3% of the human genome. One of them, Human Satellite II (HSATII), is highly expressed in several epithelial cancers and cancer cell lines. Here we report an acute induction of HSATII RNA in human cells infected with two herpes viruses. We show that human cytomegalovirus (HCMV) IE1 and IE2 proteins cooperate to induce HSATII RNA affecting several aspects of the HCMV replication cycle, viral titers and infected-cell processes. HSATII RNA expression in tissue from two chronic HCMV colitis patients correlates with the strength of CMV antigen staining. Thus, endogenous HSATII RNA synthesis after herpesvirus infections appears to have functionally important consequences for viral replication and may provide a novel insight into viral pathogenesis. The HSATII induction seen in both infected and cancer cells suggests possible convergence upon common HSATII-based regulatory mechanisms in these seemingly disparate diseases.