Importance: Biologics account for a substantial proportion of health care expenditures. Their costs have been projected to reach US $452 billion in global spending by 2022. Given recent expiration of patent protection of biologics, a shift toward greater follow-on competition among biosimilars would be expected that would allow greater uptake and lower drug costs.
View Article and Find Full Text PDFBackground: Long-term prescriptions of strong opioids for chronic noncancer pain-which are not supported by scientific evidence-suggest miscalibrated risk perceptions among those who prescribe, dispense, and take opioids. Because risk perceptions and behaviors can differ depending on whether people learn about risks through description or experience, we investigated the effects of descriptive versus simulated-experience educative formats on physicians' risk perceptions of strong opioids and their prescription behavior for managing chronic noncancer pain.
Methods: Three hundred general practitioners and 300 pain specialists in Germany-enrolled separately in two independent exploratory randomized controlled online trials-were randomly assigned to either a descriptive format (fact box) or a simulated-experience format (interactive simulation).
Background: Cancer drugs are a major component of pharmaceutical spending in the USA and Europe. The number of approved cancer drugs continues to increase. More new drugs with overlapping mechanisms of action and similar approved indications might be expected to decrease prices within drug classes.
View Article and Find Full Text PDFOvertreatment at the End of Life in Oncology The term overtreatment refers to situations, in which we evaluate the use of diagnostic or therapeutic measures negatively. On the one hand, these negative judgments refer to questionable scientific foundations of using respective measures. On the other hand, we challenge the adequacy of using medical measures in the context of overtreatment with reference to principle of beneficence.
View Article and Find Full Text PDFObjectives: Opioid prescription rates worldwide suggest miscalibrated risk perceptions among those who prescribe, dispense, and take opioids. Findings from cognitive science show that risk perceptions can differ systematically depending on whether people learn about risks by description or experience. We investigated the effects of descriptive and simulated experience risk formats on patients' risk perceptions and behavior regarding long-term strong opioid use.
View Article and Find Full Text PDFBackground: The German Hodgkin Study Group's HD18 trial established the safety and efficacy of PET-guided eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone in escalated doses) for the treatment of advanced-stage Hodgkin lymphoma. However, because of a protocol amendment during the enrolment period (June 1, 2011) that changed standard treatment from eight to six cycles, the results of the HD18 trial have been partially immature. We report a prespecified 5-year follow-up analysis of the completed HD18 trial.
View Article and Find Full Text PDFIntroduction: The US opioid crisis and increasing prescription rates in Europe suggest inappropriate risk perceptions and behaviours of people who prescribe, take or advise on opioids: physicians, patients and pharmacists. Findings from cognitive and decision science in areas other than drug safety suggest that people's risk perception and behaviour can differ depending on whether they learnt about a risk through personal experience or description. xperiencing the isk of overutilising pioids among patients with chronic on-cancer pain in mbulatory care (ERONA) is the first-ever conducted trial that aims at investigating the effects of these two modes of learning on individuals' risk perception and behaviour in the long-term administration of WHO-III opioids in chronic non-cancer pain.
View Article and Find Full Text PDFThis manuscript reviews the primary and secondary endpoints of pivotal phase III trials with immunomodulatory drugs in multiple sclerosis (MS). Considering the limitations of previous trial designs, we propose new standards for the planning of clinical trials, taking into account latest insights into MS pathophysiology and patient-relevant aspects. Using a systematic overview of published phase III (pivotal) trials performed as part of application for drug market approval, we evaluate the following characteristics: trial duration, number of trial participants, comparators, and endpoints (primary, secondary, magnetic resonance imaging outcome, and patient-reported outcomes).
View Article and Find Full Text PDFDose-dense induction with the S-HAM regimen was compared to standard double induction therapy in adult patients with newly diagnosed acute myeloid leukemia. Patients were centrally randomized (1:1) between S-HAM (2nd chemotherapy cycle starting on day 8 = "dose-dense") and double induction with TAD-HAM or HAM(-HAM) (2nd cycle starting on day 21 = "standard"). 387 evaluable patients were randomly assigned to S-HAM (N = 203) and to standard double induction (N = 184).
View Article and Find Full Text PDFThis study reports the prognostic impact of the expression of the natural killer cell marker CD56 in a large series of risk-adapted paediatric patients with T cell acute lymphoblastic leukaemia (T-ALL; n = 493) treated within the ALL-Berlin-Frankfurt-Münster (BFM) 2000 protocol. The immunophenotype was analysed centrally at diagnosis using flow cytometry and correlated with clinical parameters and outcome. CD56 expression was detected in 7·1% and early T-cell precursor (ETP) phenotype in 6·7% of all T-ALL patients.
View Article and Find Full Text PDFPurpose Somatic deletions that affect the lymphoid transcription factor-coding gene IKZF1 have previously been reported as independently associated with a poor prognosis in pediatric B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). We have now refined the prognostic strength of IKZF1 deletions by analyzing the effect of co-occurring deletions. Patients and Methods The analysis involved 991 patients with BCP ALL treated in the Associazione Italiana Ematologia ed Oncologia Pediatrica-Berlin-Frankfurt-Muenster (AIEOP-BFM) ALL 2000 trial with complete information for copy number alterations of IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A, CDKN2B, Xp22.
View Article and Find Full Text PDFWe present a 74-year-old male with nonspecific interstitial pneumonia (NSIP) during treatment with ibrutinib for mantle cell lymphoma. Previously, the patient had received six cycles of bendamustine and rituximab and six cycles of R-CHOP, followed by rituximab maintenance therapy. Respiratory tract complications of ibrutinib other than infectious pneumonia have not been mentioned in larger trials, but individual case reports hinted to a possible association with the development of pneumonitis.
View Article and Find Full Text PDFPurpose Delayed intensification (DI) is an integral part of treatment of childhood acute lymphoblastic leukemia (ALL), but it is associated with relevant toxicity. Therefore, standard-risk patients of trial AIEOP-BFM ALL 2000 (Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With ALL) were investigated with the specific aim to reduce treatment intensity. Patients and Methods Between July 2000 and July 2006, 1,164 patients (1 to 17 years of age) with standard-risk ALL (defined as the absence of high-risk cytogenetics and undetectable minimal residual disease on days 33 and 78) were randomly assigned to either experimental reduced-intensity DI (protocol III; P-III) or standard DI (protocol II; P-II).
View Article and Find Full Text PDFBackground: The intensive polychemotherapy regimen eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone in escalated doses) is very active in patients with advanced-stage Hodgkin's lymphoma, albeit at the expense of severe toxicities. Individual patients might be cured with less burdensome therapy. We investigated whether metabolic response determined by PET after two cycles of standard regimen eBEACOPP (PET-2) would allow adaption of treatment intensity, increasing it for PET-2-positive patients and reducing it for PET-2-negative patients.
View Article and Find Full Text PDFPurpose Clinical characteristics, therapeutic approaches, and prognosis of late relapse (LR) in patients with classic Hodgkin lymphoma (cHL) are poorly understood. We performed a comprehensive analysis of LR of Hodgkin lymphoma (LR-HL). Methods To estimate the incidence of LR-HL, we retrospectively analyzed 6,840 patients with cHL included in the German Hodgkin Study Group trials HD7 to HD12.
View Article and Find Full Text PDFImmunophenotyping by flow cytometry (FCM) is a worldwide mainstay in leukemia diagnostics. For concordant multicentric application, however, a gap exists between available classification systems, technologic standardization, and clinical needs. The AIEOP-BFM consortium induced an extensive standardization and validation effort between its nine national reference laboratories collaborating in immunophenotyping of pediatric acute lymphoblastic leukemia (ALL).
View Article and Find Full Text PDFPurpose: To evaluate the framework of drug information produced by public health and regulatory institutions in Europe.
Materials And Methods: We carried out a short survey asking editors of ISDB bulletins of the European region to indicate the main sources of drug information provided by public health and regulatory authorities in their countries, the specific kind of information produced and their opinions about strengths and weaknesses of such information. The availability of evaluations about the added therapeutic value of drugs and of tools facilitating the implementation of such information were particularly addressed and checked on the websites of those institutions.
Flow cytometric immunophenotyping represents an indispensable tool in hematological and immunological diagnostics. The most frequent indications include lymphocyte phenotyping and the diagnosis and monitoring of benign and malignant hematologic diseases. The role of immunophenotyping in clinical practice is evolving rapidly.
View Article and Find Full Text PDFBackground: Authors' conflicts of interest may affect the content of medical guidelines. In April 2010, the Association of Scientific Medical Societies in Germany (AWMF) issued recommendations on how such conflicts of interest should be dealt with. Most AWMF guidelines are so-called S1 guidelines developed by informal consensus in a group of experts.
View Article and Find Full Text PDFPurpose: In 1986, the risk of agranulocytosis prompted German authorities to restrict the indications for metamizole use. After an initial decline, prescriptions increased from <20 million defined daily doses in 1990 to >140 million in 2012. Concurrently, spontaneous reports of agranulocytosis increased from about 10 in 1990 to >50 in 2012.
View Article and Find Full Text PDFMultiparametric flow cytometry is an alternative approach to the polymerase chain reaction method for evaluating minimal residual disease in treatment protocols for primary acute lymphoblastic leukemia. Given considerable differences between primary and relapsed acute lymphoblastic leukemia treatment regimens, flow cytometric assessment of minimal residual disease in relapsed leukemia requires an independent comprehensive investigation. In the present study we addressed evaluation of minimal residual disease by flow cytometry in the clinical trial for childhood relapsed acute lymphoblastic leukemia using eight-color flow cytometry.
View Article and Find Full Text PDFObjectives: To better understand the molecular pathogenesis of T-cell large granular lymphocyte leukemia (T-LGL), we decided to search for those genetic alterations in T-LGL patients and MOTN-1 cell line (established from T-LGL patient) that have an impact on gene expression and as a result can influence cell biology.
Methods: Multicolor fluorescence in situ hybridization (mFISH) analysis of the MOTN-1 cell line was performed as well as paired-end next-generation sequencing (NGS; Illumina HiSeq2000) of this cell line and one T-LGL patient. In addition, chosen 6q region was characterized in three T-LGL patients using high-resolution comparative genomic hybridization (FT-CGH) and LM-PCR.