Validity and cost-effectiveness of methods for screening of primary open angle glaucoma

Health political background: About 950,000 people are affected by glaucoma in Germany, about 50% of which are undiagnosed. The German Ophthalmological Society and the German Association of Ophthalmologists recommend a screening for glaucoma according to their guidelines. The Federal Joint Committee disapproved a glaucoma-screening program on expense of the compulsory health insurance in 2004. Scientific background: Primary open angle glaucoma is diagnosed by evaluation of the optic disc, the retinal fibre layer and the visual field. The main examinations are ophthalmoscopy, scanning laser polarimetry, confocal scanning laser ophthalmoscopy, retinal thickness analysis and optical coherence tomography. Scotomas are diagnosed by perimetry (standard automated perimetry, short wavelength automated perimetry and frequency doubling perimetry). The intraocular pressure is the most important treatable risk factor and is measured by (contact or non-contact) tonometry. Research questions: The aim of this HTA-report is to investigate the diagnostic validity and cost effectiveness of diagnostic techniques or combinations of these methods with respect to the use in a screening setting in Germany. Methods: A systematic literature research was performed in 35 international databases and yielded 2602 articles. Overall 57 publications were included for assessment, according to predefined selection criteria. Results: The 55 medical articles deal mainly with frequency doubling perimetry, confocal scanning laser ophthalmoscopy and scanning laser polarimetry. Few articles cover short wavelength automated perimetry, tonometry and ophalmocopic evaluations by ophthalmologists. The quality of the papers is generally low, as far as the evidence in respect of screening is concerned. No single method exists with both, high sensitivity and high specificity for screening purpose. Data are also not sufficient to recommend combinations of methods. Only two economic models on cost-effectivenes of screening investigations could be identified. No economic evaluations of the most recent methods can be found in the published literature. A British cost-effectiveness analysis calculates cost per true positives and favours a combination of ophthalmoscopy, tonometry and perimetry either for people at high risk for glaucoma or for the total population as an initial examination. A Canadian HTA-report models the cost per year of blindness avoided. The report concludes that because of a high degree of uncertainty with respect to the benefits and the high costs involved, the setting-up of a glaucoma-screening program cannot be supported. Discussion: The literature shows that combinations of methods have to be used for screening of glaucoma in order to get reasonable values of sensitivity and specificity. Presently no combination of methods and no algorithm can be presented for glaucoma screening with sufficient evidence. Also no conclusions about cost-effectiveness for Germany can be made based on the available literature. Conclusions: In order to find the optimal combination of methods for glaucoma-screening, population-based studies have to be performed. Therefore also no final conclusions can be drawn with respect to cost-effectiveness of glaucoma-screening methods. The economic evaluation of a clinical effective screening-method should consider the effects of blindness avoided, as well as effects on the prevention of visual impairment

Evaluation of optical coherence tomography in the diagnosis of age related macula degeneration compared with fluorescence angiography

Background: In industrialised nations age-related macular degeneration (AMD) is the most common cause of blindness and severe visual impairment. AMD is a disease of the retina characterized by the accumulation of metabolic products in the macula. In early stages drusen and pigment disorders occur, in late stages a dry form is distinguished from the exsudative form with choroidal neovascularisation. AMD causes vision disorders such as blurred vision of the central part of the visual field, leading finally to a dark spot. Several therapies are available for the exsudative form, however an exact diagnosis is partially essential. The gold standard for the diagnosis of AMD is fluorescein angiography (FA), an invasive investigation with intravenous application of a dye. Optical coherence tomography (OCT) is a more recent non-invasive procedure. Objectives: The aim of this HTA report is to investigate the efficacy and efficiency of OCT compared to FA. Ethical, societal and legal aspects are also considered. Methods: A systematic literature search was performed in 34 international databases which yielded 2324 articles. Eight publications were included for assessment, according to predefined selection criteria. Results: The number of studies investigating OCT compared to FA in patients with AMD is presently very limited and the quality of the studies is generally low. The number of investigated patients is below 35 in four publications and in only one publication it is above 100. Moreover in most of the articles very selected patient groups are studied. Economic studies concerning the efficiency of OCT compared to FA cannot be identified. DiscussionEven though the patient groups investigated and the objectives of the studies are very heterogenous, all publications uniformly show that OCT cannot replace FA. However, OCT yields additional diagnostic findings and may verify unclear findings of FA. Therefore the application of OCT in addition to FA is useful in many cases. With regard to costs German patients on average currently have to pay more for performing OCT than for performing FA. Conclusion: Future studies have to show whether OCT may give diagnostic information essential for therapeutic decisions in addition to FA and whether it can replace FA in selected cases. The number of patients included in these studies should be high enough to answer relevant questions with sufficient statistical power. An economic model calculation can be built upon the resulting findings

Longevity of dental amalgam in comparison to composite materials

Health political background: Caries is one of the most prevalent diseases worldwide. For (direct) restaurations of carious lesions, tooth-coloured composite materials are increasingly used. The compulsory health insurance pays for composite fillings in front teeth; in posterior teeth, patients have to bear the extra cost. Scientific background: Amalgam is an alloy of mercury and other metals and has been used in dentistry for more than one hundred and fifty years. Composites consist of a resin matrix and chemically bonded fillers. They have been used for about fifty years in front teeth. Amalgam has a long longevity; the further development of composites has also shown improvements regarding their longevity. Research questions: This HTA-report aims to evaluate the longevity (failure rate, median survival time (MST), median age) of direct amalgam fillings in comparison to direct composite fillings in permanent teeth from a medical and economical perspective and discusses the ethical, legal and social aspects of using these filling materials. Methods: The systematic literature search yielded a total of 1,149 abstracts. After a two-step selection process based on defined criteria 25 publications remained to be assessed. Results: The medical studies report a longer longevity for amalgam fillings than for composite fillings. However, the results of these studies show a large heterogeneity. No publication on the costs or the cost-effectiveness of amalgam and composite fillings exists for Germany. The economic analyses (NL, SWE, GB) report higher costs for composite fillings when longevity is assumed equal (for an observation period of five years) or longer for amalgam compared to composite fillings. These higher costs are due to the higher complexity of placing composite fillings. Discussion: Due to different study designs and insufficient documentation of study details, a comparison of different studies on longevity of direct amalgam and composite fillings in posterior teeth is difficult. Apart from the difficulties in conducting a randomized, controlled long-term study comparing the longevity of direct fillings, the fact that composites and adhesives used in a study have often already been replaced by the next generation of the product at the time of study publication presents an additional problem. Not only the filling material, but also patient parameters and local, intraoral factors (e. g. localisation of the filling) as well as the treating dentist have an impact on the longevity of dental fillings. In evaluating economic studies, one has to refer to the heterogeneity of data on longevity in the medical evaluation. The only effect parameter used in the studies is longevity, other aspects (e. g. long-term functionality) are only referred to in discussions. Extensive counselling of patients regarding the selection of the appropriate filling material is important. Conclusions: Amalgam fillings show a longer longevity than composite fillings. Two out of six systematic reviews conclude that the expected survival time of composite fillings can be comparable to amalgam fillings. However, these conclusions are based on the results of short-term studies which usually overestimate the longevity of filling materials. From an economic standpoint, amalgam is the more economic filling material compared to direct composite fillings in posterior teeth when considering longevity as the only result parameter. Other aspects than longevity need to be considered in individually choosing the appropriate dental filling material. For future studies aiming to compare the longevity of amalgam and composite fillings, a sufficient sample size and study period, preferably in the setting of a private dental practice, should be aimed for. An evaluation of the cost-effectiveness of amalgam and composite fillings should take the functionality of teeth over a longer time period into account, as well as patients’ preferences. The rapid development of composite materials and adhesives make short term revisions of these conclusions necessary

Effectiveness and efficiency of CT-colonography compared to conventional colonoscopy for the early detection and diagnosis of colorectal cancer

Health political background Colorectal cancer (CC) is the second most common cancer and cause of cancer death for both men and women in Germany. Various methods for early detection of CC exist, including conventional coloscopy which is reimbursed within the scope of cancer screening, as well as computertomography-coloscopy (CTC) which is currently not reimbursed. Scientific background CTC is a mere diagnostic procedure which has a lower risk of perforation than conventional coloscopy. However, as it is an x-ray procedure, it exposes the patient to radiation. Conventional coloscopy is considered the gold standard due to its high sensitivity and specificity for locating adenomas. Furthermore, it offers the advantage that in addition to extended diagnostic measures therapeutic measures can be undertaken during the procedure. Research questions This HTA-report aims to evaluate the effectiveness and efficiency of CTC in comparison to conventional coloscopy in the early detection and diagnosis of colorectal cancer and/or its precursors and which ethical and legal aspects have to be considered. Methods The systematic literature search (27 international literature data bases) yielded a total of 1,713 abstracts. After a two-step selection process 36 publications remained to be assessed. Results The results regarding the effectivity of CTC in diagnosis and screening for colorectal cancer and/or its precursors are partly promising, however, they are very heterogeneous. Therefore, regarding its sensitivity and specificity, CTC cannot be considered an equivalent alternative to conventional coloscopy for diagnosis and screening. The heterogeneity of results is due to technical (device type, settings), patient dependent (preparation) and operator dependent (training) factors. No economic results for a comparison of the procedures for diagnosis exist. Regarding the cost-effectiveness of a CTC-screening, international model calculations are available. According to this calculation, the CTC-screening is cost-effective compared to the option 'no screening'; however, conventional coloscopy-screening is generally more cost-effective. Discussion If modern CTC-devices are used with adequate technical settings, software, appropriate patient preparation and training of the operator, better results regarding sensitivity can be expected. Basically, the fact that no therapeutic measures (polypectomy) can be taken during CTC compared to conventional coloscopy needs to be considered. Unanswered medical questions pertain to the interval of examinations for screening (considering the radiation exposure), the approach to small polyps and the significance of flat and depressed lesions. Regarding its cost-effectiveness, conventional coloscopy-screening results in greater health benefits and lower costs than CTC-screening in most model calculations. These results cannot be applied to Germany directly. An important ethical aspect is the consideration of patient preferences regarding the procedures. Legal aspects concern the stipulation and maintenance of quality standards. Conclusions At this time, a clear endorsement of CTC as an alternative procedure for diagnosis and screening to the current gold standard conventional coloscopy cannot be given. On the basis of the available literature this holds true for both the medical as well as the economic assessment. However, despite the numerous studies and analyses on this topic, this assessment is afflicted with uncertainties. Due to the rapid development of CTC, short term revisions of these research questions are needed.Gesundheitspolitischer Hintergrund Darmkrebserkrankungen/kolorektale Karzinome (KRK) stellen in Deutschland für beide Geschlechter die zweithäufigste Krebserkrankung und Krebstodesursache dar. Verschiedene Verfahren zur Früherkennung von KRK stehen zur Verfügung, darunter die konventionelle Koloskopie, die im Rahmen der Krebsfrüherkennung erstattet wird, sowie die Computertomografie-Koloskopie (CTC), die derzeit nicht erstattet wird. Wissenschaftlicher Hintergrund Die CTC ist ein rein diagnostisches Verfahren, das ein geringeres Komplikationsrisiko durch Perforation aufweist als die konventionelle Koloskopie, jedoch als Röntgenverfahren mit einer Strahlenbelastung behaftet ist. Die konventionelle Koloskopie gilt aufgrund ihrer hohen Sensitivität und Spezifität für das Auffinden von Adenomen und KRK als Goldstandard und bietet den Vorteil, neben erweiterten diagnostischen auch therapeutische Maßnahmen zu ermöglichen. Fragestellung In diesem HTA-Bericht soll geklärt werden, welche Effektivität und Effizienz die CTC im Vergleich zur konventionellen Koloskopie in der Früherkennung und Diagnose von Dickdarmkrebs und/oder Vorstufen desselben hat und welche ethischen und juristischen Aspekte zu beachten sind. Methodik Die systematische Literatursuche (27 internationale Literaturdatenbanken) ergab 1.713 Zusammenfassungen. Nach einem zweiteiligen Selektionsprozess verbleiben 36 bewertete Publikationen. Ergebnisse Die Ergebnisse zur Effektivität der CTC in Diagnostik und Screening von Dickdarmkrebs und/oder Vorstufen sind teilweise vielversprechend, aber sehr heterogen. Sowohl in der Diagnostik als auch zum Screening kann die CTC deshalb hinsichtlich ihrer Erkennungsgüte derzeit nicht als gleichwertige Alternative zur konventionellen Koloskopie gesehen werden. Für die Heterogenität der Ergebnisse sind technische (Gerätetyp, Einstellungen), patienten- (Vorbereitung) und befunderbezogene (Ausbildung) Faktoren verantwortlich. Einzelne Indikationen zur Diagnostik des KRK mittels CTC liegen vor. Ökonomische Ergebnisse zum Verfahrensvergleich in der Diagnostik liegen nicht vor. Zur Kosteneffektivität eines CTC-Screenings finden sich ausländische Modellrechnungen, aufgrund derer das CTC-Screening zwar als kosteneffektiv zur Option "kein Screening" bezeichnet werden kann, das Screening mit konventioneller Koloskopie jedoch generell kosteneffektiver ist. Diskussion Bei Verwendung moderner CTC-Geräte mit entsprechender technischer Einstellung, Software, adäquater Patientenvorbereitung und Ausbildung der Befunder sind bessere Ergebnisse hinsichtlich der Sensitivität zu erwarten. Prinzipiell ist bei der CTC die im Vergleich zur Koloskopie fehlende Therapiemöglichkeit (Polypektomie) zu berücksichtigen. Offene medizinische Fragen betreffen das Untersuchungsintervall bei Screeninguntersuchungen (unter Berücksichtigung der Strahlenbelastung), die Vorgangsweise bei kleinen Polypen und die Bedeutung von flachen bzw. eingesunkenen Läsionen. Hinsichtlich der Kosteneffektivität führt das Koloskopiescreening in den meisten modellierten Szenarien zu größeren Gesundheitseffekten bei gleichzeitig geringeren Kosten als das CTC-Screening. Diese Ergebnisse können nicht direkt auf Deutschland übertragen werden. Ein wichtiger (auch ethischer) Aspekt ist die Berücksichtigung der Patientenpräferenzen hinsichtlich der Untersuchungen. Juristische Aspekte betreffen insbesondere auch die Vorschreibung und Einhaltung von Qualitätsstandards. Schlussfolgerung Eine klare Empfehlung für die CTC als alternatives Verfahren zum bisherigen Goldstandard konventionelle Koloskopie kann derzeit weder für die Diagnose- noch für die Screeningsituation gegeben werden. Dies gilt aufgrund der vorliegenden Literatur sowohl für die medizinische als auch für die ökonomische Bewertung, ist jedoch trotz der zahlreichen Studien und Analysen zu diesem Thema mit Unsicherheiten behaftet. Wegen der schnellen Weiterentwicklung der CTC sind zu dieser Fragestellung kurzfristige Updates erforderlich

Effectiveness and efficiency of CT-colonography compared to conventional colonoscopy for the early detection and diagnosis of colorectal cancer

Health political background: Colorectal cancer (CC) is the second most common cancer and cause of cancer death for both men and women in Germany. Various methods for early detection of CC exist, including conventional coloscopy which is reimbursed within the scope of cancer screening, as well as computertomography-coloscopy (CTC) which is currently not reimbursed. Scientific background: CTC is a mere diagnostic procedure which has a lower risk of perforation than conventional coloscopy. However, as it is an x-ray procedure, it exposes the patient to radiation. Conventional coloscopy is considered the gold standard due to its high sensitivity and specificity for locating adenomas. Furthermore, it offers the advantage that in addition to extended diagnostic measures therapeutic measures can be undertaken during the procedure. Research questions: This HTA-report aims to evaluate the effectiveness and efficiency of CTC in comparison to conventional coloscopy in the early detection and diagnosis of colorectal cancer and/or its precursors and which ethical and legal aspects have to be considered. Methods: The systematic literature search (27 international literature data bases) yielded a total of 1,713 abstracts. After a two-step selection process 36 publications remained to be assessed. Results: The results regarding the effectivity of CTC in diagnosis and screening for colorectal cancer and/or its precursors are partly promising, however, they are very heterogeneous. Therefore, regarding its sensitivity and specificity, CTC cannot be considered an equivalent alternative to conventional coloscopy for diagnosis and screening. The heterogeneity of results is due to technical (device type, settings), patient dependent (preparation) and operator dependent (training) factors. No economic results for a comparison of the procedures for diagnosis exist. Regarding the cost-effectiveness of a CTC-screening, international model calculations are available. According to this calculation, the CTC-screening is cost-effective compared to the option ‘no screening’; however, conventional coloscopy-screening is generally more cost-effective.DiscussionIf modern CTC-devices are used with adequate technical settings, software, appropriate patient preparation and training of the operator, better results regarding sensitivity can be expected. Basically, the fact that no therapeutic measures (polypectomy) can be taken during CTC compared to conventional coloscopy needs to be considered. Unanswered medical questions pertain to the interval of examinations for screening (considering the radiation exposure), the approach to small polyps and the significance of flat and depressed lesions. Regarding its cost-effectiveness, conventional coloscopy-screening results in greater health benefits and lower costs than CTC-screening in most model calculations. These results cannot be applied to Germany directly. An important ethical aspect is the consideration of patient preferences regarding the procedures. Legal aspects concern the stipulation and maintenance of quality standards. Conclusions: At this time, a clear endorsement of CTC as an alternative procedure for diagnosis and screening to the current gold standard conventional coloscopy cannot be given. On the basis of the available literature this holds true for both the medical as well as the economic assessment. However, despite the numerous studies and analyses on this topic, this assessment is afflicted with uncertainties. Due to the rapid development of CTC, short term revisions of these research questions are needed

Atypical antipsychotic poisoning in young children: a multicentre analysis of poisons centres data

Although paediatric patients frequently suffer from intoxications with atypical antipsychotics, the number of studies in young children, which have assessed the effects of acute exposure to this class of drugs, is very limited. The aim of this study was to achieve a better characterization of the acute toxicity profile in young children of the atypical antipsychotics clozapine, olanzapine, quetiapine, and risperidone. We performed a multicentre retrospective analysis of cases with atypical antipsychotics intoxication in children younger than 6years, reported by physicians to German, Austrian, and Swiss Poisons Centres for the 9-year period between January 1, 2001 and December 31, 2009. One hundred and six cases (31 clozapine, 29 olanzapine, 12 quetiapine, and 34 risperidone) were available for analysis. Forty-seven of the children showed minor, 28 moderate, and 2 severe symptoms. Twenty-nine cases were asymptomatic. No fatalities were recorded. Symptoms predominantly involved the central nervous and cardiovascular systems. Minor reduction in vigilance (Glasgow Coma Scale score >9) (62%) was the most frequently reported symptom, followed by miosis (12%) and mild tachycardia (10%). Extrapyramidal motor symptoms were observed in one case (1%) after ingestion of risperidone. In most cases, surveillance and supportive care were sufficient to achieve a good outcome, and all children made full recovery. Conclusions: Paediatric antipsychotic exposure can result in significant poisoning; however, in most cases only minor or moderate symptoms occurred and were followed by complete recovery. Symptomatic patients should be monitored for central nervous system depression and an electrocardiogram should be obtained