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Jos P. M. Diederiks - One of the best experts on this subject based on the ideXlab platform.
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The development of a short Generic Version of the Sickness Impact Profile.
Journal of clinical epidemiology, 1994Co-Authors: A.f. De Bruin, Jos P. M. Diederiks, L.p. De Witte, Fred C.j. Stevens, Hans PhilipsenAbstract:Abstract This study concerns the development of a short Version of a well-known and much used clinimetric instrument called the Sickness Impact Profile (SIP). The SIP is a Generic measure of functional status. Based on findings of a principal components analysis of over 800 SIPS from a multi-diagnostic population, a selection of 68 items divided over 6 dimensions was made and initially tested. As no support was found for the statistical validity of the categorical structure of the original SIP, a new structure, discovered through principal components analysis, was used as the basis for selecting items. Comparison of the scores on the selection with information provided by the original SIP showed very promising results: the 68 item selection may serve as a valid short SIP-Version.
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The sickness impact profile: SIP68, a short Generic Version. First evaluation of the reliability and reproducibility.
Journal of clinical epidemiology, 1994Co-Authors: A.f. De Bruin, L.p. De Witte, M. Buys, Jos P. M. DiederiksAbstract:In previous research a short Version of the Sickness Impact Profile (SIP136) was developed, containing 68 items. This SIP68 is intended as a short Generic alternative to the original SIP. High reliability of the SIP68 was reported when it was extracted from the SIP136. This paper is a report on the first reliability testing of the SIP68 administered as an independent instrument without the context of the SIP136. To establish the test-retest reliability and the internal consistency of the new instrument, 51 patients of an outpatient department of rheumatology completed the SIP68 twice, with an interval of 48 hours. To compare the performance of the independent SIP68 with the SIP68 extracted from the SIP136, the SIP136 also was completed two times by the same 51 respondents. Test-retest reliability for both administration types was assessed by means of the intraclass correlation coefficient and the Jaccard's similarity ratio. Internal consistency was assessed by means of Cronbach's alpha. The reliability appears to be high in both the independent SIP68 as well as the extracted SIP68. Moreover, the reliability of the independent SIP68 appears to be as high as for the SIP136. These findings were very encouraging, indicating that the SIP68 may very well serve as a Generic alternative to the SIP136.
A.f. De Bruin - One of the best experts on this subject based on the ideXlab platform.
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The development of a short Generic Version of the Sickness Impact Profile.
Journal of clinical epidemiology, 1994Co-Authors: A.f. De Bruin, Jos P. M. Diederiks, L.p. De Witte, Fred C.j. Stevens, Hans PhilipsenAbstract:Abstract This study concerns the development of a short Version of a well-known and much used clinimetric instrument called the Sickness Impact Profile (SIP). The SIP is a Generic measure of functional status. Based on findings of a principal components analysis of over 800 SIPS from a multi-diagnostic population, a selection of 68 items divided over 6 dimensions was made and initially tested. As no support was found for the statistical validity of the categorical structure of the original SIP, a new structure, discovered through principal components analysis, was used as the basis for selecting items. Comparison of the scores on the selection with information provided by the original SIP showed very promising results: the 68 item selection may serve as a valid short SIP-Version.
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The sickness impact profile: SIP68, a short Generic Version. First evaluation of the reliability and reproducibility.
Journal of clinical epidemiology, 1994Co-Authors: A.f. De Bruin, L.p. De Witte, M. Buys, Jos P. M. DiederiksAbstract:In previous research a short Version of the Sickness Impact Profile (SIP136) was developed, containing 68 items. This SIP68 is intended as a short Generic alternative to the original SIP. High reliability of the SIP68 was reported when it was extracted from the SIP136. This paper is a report on the first reliability testing of the SIP68 administered as an independent instrument without the context of the SIP136. To establish the test-retest reliability and the internal consistency of the new instrument, 51 patients of an outpatient department of rheumatology completed the SIP68 twice, with an interval of 48 hours. To compare the performance of the independent SIP68 with the SIP68 extracted from the SIP136, the SIP136 also was completed two times by the same 51 respondents. Test-retest reliability for both administration types was assessed by means of the intraclass correlation coefficient and the Jaccard's similarity ratio. Internal consistency was assessed by means of Cronbach's alpha. The reliability appears to be high in both the independent SIP68 as well as the extracted SIP68. Moreover, the reliability of the independent SIP68 appears to be as high as for the SIP136. These findings were very encouraging, indicating that the SIP68 may very well serve as a Generic alternative to the SIP136.
Hans Philipsen - One of the best experts on this subject based on the ideXlab platform.
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The development of a short Generic Version of the Sickness Impact Profile.
Journal of clinical epidemiology, 1994Co-Authors: A.f. De Bruin, Jos P. M. Diederiks, L.p. De Witte, Fred C.j. Stevens, Hans PhilipsenAbstract:Abstract This study concerns the development of a short Version of a well-known and much used clinimetric instrument called the Sickness Impact Profile (SIP). The SIP is a Generic measure of functional status. Based on findings of a principal components analysis of over 800 SIPS from a multi-diagnostic population, a selection of 68 items divided over 6 dimensions was made and initially tested. As no support was found for the statistical validity of the categorical structure of the original SIP, a new structure, discovered through principal components analysis, was used as the basis for selecting items. Comparison of the scores on the selection with information provided by the original SIP showed very promising results: the 68 item selection may serve as a valid short SIP-Version.
L.p. De Witte - One of the best experts on this subject based on the ideXlab platform.
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The development of a short Generic Version of the Sickness Impact Profile.
Journal of clinical epidemiology, 1994Co-Authors: A.f. De Bruin, Jos P. M. Diederiks, L.p. De Witte, Fred C.j. Stevens, Hans PhilipsenAbstract:Abstract This study concerns the development of a short Version of a well-known and much used clinimetric instrument called the Sickness Impact Profile (SIP). The SIP is a Generic measure of functional status. Based on findings of a principal components analysis of over 800 SIPS from a multi-diagnostic population, a selection of 68 items divided over 6 dimensions was made and initially tested. As no support was found for the statistical validity of the categorical structure of the original SIP, a new structure, discovered through principal components analysis, was used as the basis for selecting items. Comparison of the scores on the selection with information provided by the original SIP showed very promising results: the 68 item selection may serve as a valid short SIP-Version.
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The sickness impact profile: SIP68, a short Generic Version. First evaluation of the reliability and reproducibility.
Journal of clinical epidemiology, 1994Co-Authors: A.f. De Bruin, L.p. De Witte, M. Buys, Jos P. M. DiederiksAbstract:In previous research a short Version of the Sickness Impact Profile (SIP136) was developed, containing 68 items. This SIP68 is intended as a short Generic alternative to the original SIP. High reliability of the SIP68 was reported when it was extracted from the SIP136. This paper is a report on the first reliability testing of the SIP68 administered as an independent instrument without the context of the SIP136. To establish the test-retest reliability and the internal consistency of the new instrument, 51 patients of an outpatient department of rheumatology completed the SIP68 twice, with an interval of 48 hours. To compare the performance of the independent SIP68 with the SIP68 extracted from the SIP136, the SIP136 also was completed two times by the same 51 respondents. Test-retest reliability for both administration types was assessed by means of the intraclass correlation coefficient and the Jaccard's similarity ratio. Internal consistency was assessed by means of Cronbach's alpha. The reliability appears to be high in both the independent SIP68 as well as the extracted SIP68. Moreover, the reliability of the independent SIP68 appears to be as high as for the SIP136. These findings were very encouraging, indicating that the SIP68 may very well serve as a Generic alternative to the SIP136.
Jawed Fareed - One of the best experts on this subject based on the ideXlab platform.
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Comparative Studies on a Branded Recombinant Factor VIIa and Its Generic Version to Demonstrate Bioequivalence
Blood, 2017Co-Authors: Nasir Sadeghi, Debra Hoppensteadt, Jawed Fareed, Jeanine M. Walenga, Zafar Siddiqui, Omer Iqbal, Schuharazad Abro, Michael J. Mosier, Ahmed KoutaAbstract:Background: Recombinant factor VIIa (NovoSeven® Copenhagen, Denmark) is used in the management of bleeding in patients with hemophilia. A Generic biosimilar Version of NovoSeven® is also developed for the same indication (AryoSeven™, AryoGen, Tehran-Iran). These Generic Versions of rFVIIa are claimed to be biosimilar to the Novoseven. The purpose of this study is to compare several batches of Generic Versions of rFVIIa namely, Aryoseven with multiple commercially available batches of branded Novoseven to determine bioavailability. Methods: Four commercially available random lots of Novoseven were obtained through US and European sources and compared to 5 clinical batches of Aryoseven obtained from Aryogen (Tehran, Iran). These drugs were diluted with saline to make a stock solution of 1mg/ml. Further dilutions were made to obtain working concentrations of 100, 10, 1 and 0.1 µg/ml. Molecular profile using surface enhanced laser desorption ionization (SELDI), gel electrophoretic profile (GEP), immunoblotting studies, and procoagulant activity as measured by clot based method were carried out. Thrombin generation studies were carried out after supplementing with NHP at 0-1.0 ug/ml. The pharmacokinetic profile of one representative batch of Novoseven and Aryoseven was studied in primates after a 50 ug/ml bolus IV in terms of factor VIIa levels. Results: The SELDI mass spectrometric profile of all rFVIIa preparations were comparable. The GEP and immunoblotting studies of the two groups of agents showed a comparable profile with distinct peaks at 50 KDa and 29 KDa. In the clot based functional assays performed in the citrated whole blood and retrieved plasma the two batches of FVIIa produced comparable procoagulant effects in the PT and aPTT assays. In the 0.25 - 1.0 µg/ml range in comparison to the control with saline supplementation, the aPTT did not exhibit any significant shortening whereas there was a sharpening of PT values in the whole blood which was identical in both the AryoSeven™ and NovoSeven® preparations. In the retrieved plasma both products produced comparable effect on the PT and aPTT assays. In platelet rich plasma (PRP) and platelet poor plasma (PPP) AryoSeven and NovoSeven at graded concentration of 0.125 to 1 µg/ml did not produce any measurable change in both PT and aPTT assays. The correction studies carried out in the FVII deficient plasma at a concentration range of 1 to 0.01 µg/ml did not reveal any differences between 2 groups of drugs. The relative correction was comparable in all concentrations for the 2 tissue factor reagents namely Innovin and Recomboplastin 2G. The results were indistinguishable for the 2 groups of drugs. The effect of NovoSeven® and AryoSeven™ on the reversal of anticoagulation in orally anticoagulated patients9 were similar in relative correction of the plasma INR for the 2 groups of FVIIa preparations in the range of 0.03 to 1 µg/ml. In the thrombin generation studies both the Novoseven and Aryoseven produced similar effects as measured by increased thrombin generation. In the primate pharmacokinetic studies both groups exhibited similar pharmacokinetic profile. Conclusions: These results demonstrate that four batches of Novoseven and 5 individual clinical batches of Aryoseven were found to be biosimilar. The pharmacokinetic profile of the Novoseven and Aryoseven were studied in primates measuring the factor VIIa level for 6 hours and were found to be comparable. Thus, the Generic Aryoseven is biosimilar to branded Novoseven and warrants further validation studies. Disclosures No relevant conflicts of interest to declare.
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A Generic Version of Recombinant FVIIa Is Similar to the Branded Product (NovoSeven)
Blood, 2015Co-Authors: Nasir Sadeghi, Paul O'malley, Daniel Kahn, Debra Hoppensteadt, Jawed FareedAbstract:Abstract Background: Commercially available recombinant factor VIIa (Novoseven) is widely used in the management of hemophilia patients with inhibitors. Recently several Generic Versions of recombinant VIIa (rFVIIa) have become available. The Generic Versions of rFVIIa are claimed to be biosimilar to the barnded Novoseven (Novo Nordisk, Copenhagen, Denmark). The purpose of this study is to compare the US and European Novoseven products with a Generic Version of rFVIIa namely, Aryoseven (Aryogen, Tehran, Iran). Methods: Four commercially available random lots of Novoseven were obtained from the US and European sources. Four different batches of Aryoseven were obtained from Aryogen. All individual rFVIIa preparations were diluted to obtain working concentrations of 100, 10, 1 and 0.1 ug/ml. Protein content (Lowry's method), molecular profile using surface enhanced laser desorption ionization (SELDI), gel electrophoretic profile (GEP), factor VII related antigen level (FVII:Ag), factor VII correction studies in depleted plasma and thrombin generation (TG) studies were carried out. In addition, VIIa/tissue factor mediated thrombin generation studies were carried out in various prothrombin complex concentrates such as Beriplex and Prothromplex. Results: The protein content and SELDI mass spectrophotometric profile of all 4 rFVIIa preparations were comparable. There was no differences in the Novoseven obtained from the US and European sources. The GEP of the two groups of agents showed a comparable profile with distinct peaks at 50 KDa and 25 KDa. The FVII related antigen levels were also comparable in the Novoseven and Aryoseven preparations. Supplementation of both the Novoseven and Aryoseven preparations at 10 and 100 ug/ml resulted in a comparable correction of the factor VII deficient plasma as measured by PT(INR). Thrombin generation was comparable in the branded and Generic product. Conclusions: These results demonstrate that the US and European Aryoseven are comparable. Four batches of Novoseven and 4 individual clinical batches of Aryoseven were found to be comparable. When the US purchased Novoseven preparation was compared with the European Novoseven product, no differences were noted. Thus, the Generic Aryoseven is biosimilar to barnded Novoseven and warrant in vivo validation studies. Disclosures No relevant conflicts of interest to declare.
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Comparative Studies On Branded Enoxaparin and a US Generic Version of Enoxaparin.
Blood, 2012Co-Authors: Jeanine M. Walenga, Debra Hoppensteadt, Jawed Fareed, Walter Jeske, Josephine Cunanan, Vicki Escalante, Hussein Khan, Joseph Bailey, Mamdouh BakhosAbstract:Abstract 2264 Background: Low molecular weight heparins (LMWHs) are complex biologic drugs whose heterogeneity in saccharide chain length and in the composition (sulfate, acetyl), content, and location of functional groups can impact their multiple biologic activities. Enoxaparin (Lovenox®) is validated for multiple indications and is the most widely used LMWH in the US. Several Generic Versions of enoxaparin are currently available in the US. We undertook this study to compare the activity profile of branded and a Generic enoxaparin. Methods: Five batches each of branded (B; Sanofi-aventis; Bridgewater, NJ) and Generic (G; Sandoz US; Princeton, NJ) enoxaparin were studied. Drugs were purchased through hospital pharmacies as pre-filled syringes containing 40 mg drug. The molecular weight profile of each batch of LMWH was determined using HPLC. To analyze in vitro activities, LMWHs were supplemented to normal human plasma and assessed using amidolytic anti-FXa and anti-FIIa, fibrinokinetic, and thrombin generation assays. Human whole blood was supplemented with LMWHs and the dynamic blood coagulation process was analyzed by thrombelastography (TEG). Whole blood flow cytometry was used to assess the ability of the LMWHs to inhibit tissue factor (TF)-induced platelet activation and lipopolysaccharide (LPS)-induced neutrophil activation. To assess the in vivo effect of the LMWHs, primates treated subcutaneously with a dose of 1 mg/kg LMWH had blood samples drawn pre-treatment and at 4, 6, 12 and 24 hours. Ex vivo pharmacodynamic activities of TFPI release, TAFI inhibition, and thrombin generation inhibition were evaluated. Results: Molecular weight parameters and IC 50 values for FXa and FIIa inhibition by branded and Generic enoxaparin were comparable. In the in vitro thrombin generation and fibrinokinetic assays, branded enoxaparin exhibited a more potent anticoagulant effect demonstrating slower clot formation with a weaker final clot structure ( p =0.01) than Generic enoxaparin. Although both the branded and Generic enoxaparin produced a concentration-dependent anticoagulant effect in the TEG, there was greater degree of variability for the Generic product between blood donors and between batches resulting in a less predictable linear response as drug concentration increased. When the increase in TEG R-time was plotted vs. concentration, branded enoxaparin showed a stronger anticoagulant effect ( p =0.05). A concentration-dependent reduction in TF-induced platelet P-selectin expression was observed with branded and Generic enoxaparin producing a similar effect. Incubation of whole blood with LPS resulted in a dramatic increase in neutrophil CD11b expression (MFI: 13.1±2.8 vs. 249.0±42.1) which was reduced by increasing concentrations of LMWH. This effect appeared to be stronger for Generic than branded enoxaparin (MFI: 165.2±31.9 vs. 208.9±25.9). In primates treated with branded and Generic enoxaparin, anti-FXa activity assessed by AUC 0–24hrs was similar. Anti-FIIa activity, however, was significantly higher in primates treated with Generic enoxaparin (135±28 vs. 91±20 (μg*hr)/ml; p =0.023). AUC for thrombin generation inhibition was (B) 932±59 vs. (G) 775±119 %inhibition*hr; p =0.029. AUC for TFPI release was (B) 1101±98 vs . (G) 822±13 (ng/*hr)/ml; p =0.006. AUC for inhibition of TAFI activation was (B) 780±73 vs. 906±69 % inhibition*hr; p =0.023. Conclusions: This investigation demonstrated a wider variation in anticoagulant response to Generic enoxaparin in comparison to branded enoxaparin. This variation was due to the response of the individual subject as well as to the batch of the product. In addition, both in vitro and in vivo/ex vivo activity differences were observed between branded and Generic enoxaparin in several parameters relevant to the antithrombotic effect of LMWH. These findings suggest that simple analytical characterization can establish good quality control in manufacturing but may not assure similarity in biological performance between branded and Generic enoxaparin. Thus beside the routinely required characterization, inclusion of additional tests for biologic activities and pharmacodynamic profiling of Generic products in animal models may provide useful information on the bioequivalence of the Generic Versions of enoxaparin. Disclosures: Walenga: Sanofi-Aventis, Paris, France: Research Funding. Jeske: Sanofi-Aventis, Paris, France: Research Funding. Hoppensteadt: Sanofi-Aventis, Paris, France: Research Funding. Cunanan: Sanofi-Aventis, Paris, France: Research Funding. Escalante: Sanofi-Aventis, Paris, France: Research Funding. Khan: Sanofi-Aventis, Paris, France: Research Funding. Bailey: Sanofi-Aventis, Paris, France: Research Funding. Fareed: Sanofi-Aventis, Paris, France: Research Funding. Bakhos: Sanofi-Aventis, Paris, France: Research Funding.
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Comparative Studies on Branded Enoxaparin and a US Generic Version of Enoxaparin
Clinical and applied thrombosis hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis Hemostasis, 2012Co-Authors: Jeanine M. Walenga, Debra Hoppensteadt, Jawed Fareed, Walter Jeske, Josephine Cunanan, Vicki Escalante, Hussein Khan, Mamdouh BakhosAbstract:Enoxaparin, a complex, biologically derived low-molecular-weight heparin, is approved for a range of clinical indications. This study was carried out to compare the potency profile and pharmacodynamic responses of branded enoxaparin (Lovenox; Sanofi, US) with a Generic enoxaparin (enoxaparin sodium injection, USP). Five batches of each product were tested. Although the average molecular weight, anti-factor Xa, and anti-factor IIa potencies were similar for the two products, differences were observed in the in vitro thrombin generation and kinetics of clot formation (P = .01) and in the ex vivo pharmacodynamics regarding thrombin generation inhibition (P = .029), tissue factor pathway inhibitor release (P = .006), and inhibition of the active form of thrombin-activated fibrinolysis inhibitor (P = .023). These findings suggest that simple analytical characterization can establish good quality control in manufacturing, but they may not assure similarity in biological performance between the branded and the Generic enoxaparin.
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Should Generic Versions of Low Molecular Weight Heparins Be Considered As Generic or Biosimilar Drugs. A Regulatory Dilemma
Blood, 2011Co-Authors: Jawed Fareed, Debra Hoppensteadt, Walter Jeske, Rakesh Wahi, Russell D. HullAbstract:Abstract Abstract 4328 The patent protections for the low molecular weight heparin (LMWHs) enoxaparin, dalteparin and tinzaparin have expired and their Generic respective Versions are available. Despite widespread clinical use the global regulatory pathways to develop and approve these products remain unclear. In South America and Southeast Asia Generic Versions of LMWHs are available without adequate regulatory oversight. The EMEA has considered these agents as biosimilars and require both pharmaceutical and clinical data for approval. Unlike the EMEA, the US FDA requires data on the basic, chemical, and pharmacologic profiles without any clinical validation. In July 2010, the FDA approved a Generic Version of enoxaparin for all of the clinical indications for which the branded enoxaparin is approved. On the other hand, Initially the FDA had approved the different branded LMWHs as distinct drug entities, requiring clinical trials for each individual clinical indication. Generic enoxaparins from various manufacturers are marketed under different trade names even when they are manufactured by the same company. Although in the pharmacopeial assays these agents exhibit comparability, in the pharmacodynamic studies assay based differences have been reported. In a study conducted on two batches of Sandoz’s enoxaparin and Lovenox®, while no differences were noted in the molecular profile and anti-FXa activity, significant differences were noted in other assays such as thrombin generation inhibition and PF4 titration. Moreover, pharmacodynamic differences in primates after sc administration were also noted which were more obvious in the release of tissue factor pathway inhibitor and thrombin activatable fibrinolysis inhibitor assays (TAFI).As the manufacturing process of these agents may differ from manufacturer to manufacturer it is likely that certain compositional variations are not detectable by chemical methods. Thus the requirement of clinical trials to assure the safety and efficacy of these agents is an important consideration. Of concern is the disharmonization of pathways between different regulatory bodies which contribute to the complexity of this issue. It is proposed that the EMEA, FDA and other regulatory bodies develop some common global guidelines for the rationale development of these drugs. Disclosures: No relevant conflicts of interest to declare.