- Email: [email protected]
Does Patient Health Empowerment Go Hand in Hand with Privacy Empowerment?
Oral Communications Medicines Communications Using Digital Media: Findings from a Survey of Member Organisations of the European Medicines Agency’s Patients and Consumers and Health Professionals Working Parties (PCWP and HCPWP) D.R.J. Singer1,2; I. Silva2; and Mavris2⁎ European Association for Clinical Pharmacology and Therapeutics, London, United Kingdom; and 2European Medicines Agency, London, United Kingdom Background: Social media are electronic communication tools with the potential to change how policy makers, healthcare professionals, researchers, patients and consumers manage and share digital information about safe and effective use of medicines. Methods: The EMA set up an ad hoc group with representatives from its Healthcare Professionals Working Party (HCPWP) and Patients and Consumers Working Party (PCWP) to reflect on the uses of social media (Social Media Topic Group [SMTG]). A piloted qualitative survey to map current practices and expectations regarding social media was sent by the SMTG to all 65 PCWP and HCPWP member organisations. Results: Responses were obtained from 28 organisations actively using social media and 3 member organisations not actively using social media. Six (22%) of 27 respondents declared a formal communications strategy. Ten (36%) organisations reported using social media for safety alerts and 9 (32%) for regulatory updates. Direct, rapid contact with target audiences was considered a major strength. Major concerns included that messages could be perceived as oversimplified or even misinterpreted due to content restrictions, leading to potential reputational risk; and no guarantee of safety alerts reaching target audiences, in part due to variations in uptake and choice of social media tools across the EU. Opportunities included providing ways for patients with a functional loss to engage in peer-support networks; raising awareness of clinical disorders and sharing best practices on their treatment; enhancing impact when lobbying policy makers to increase support for treatment of unmet needs. Conclusions: There was a consensus that effective use of social media by patient, consumer and healthcare professional organisations offers major potential health benefits but is not risk-free, with concerns about costs and potential threats from using social media. There is clear scope for evaluating cost-effective ways of using social media for health-related organisations to contribute to safe and effective use of medicines. 1
Cost-Effectiveness of Genotype-Guided Warfarin Dosing in the Patients with Mechanical Heart Valve Replacement Under Fee-For-Service System D.-J. Kim1; H.-S. Kim1,2; M.K. Oh1; E.-Y. Kim1,2; and J.-G. Shin1,2 Inje University College of Medicine, Busan, South Korea; and 2 Inje University Busan Paik Hospital, Busan, South Korea Background: Although studies assessing the cost-effectiveness of genotype-guided warfarin dosing for the management of atrial fibrillation and venous thromboembolism have been reported, no publications have addressed genotype-guided warfarin therapy in mechanical heart valve replacement (MHVR) patients or genotype-guided warfarin therapy under the fee-for-service insurance system. The aim of this study was to evaluate the cost-effectiveness of genotype-guided warfarin dosing in patients with MHVR under the fee-for-service system from the Korea healthcare sector perspective. Methods: A decision-analytic Markov model was developed to evaluate the cost-effectiveness of genotype-guided warfarin dosing compared to standard dosing. Estimates of clinical adverse event rates
1
August 2017
and health state utilities were derived from the published literature. The outcome measure was the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were performed to explore the range of plausible results. Results: In a base-case analysis, genotype-guided warfarin dosing was associated with marginally higher QALYs compared to standard warfarin dosing (6.088 vs. 6.083, respectively), at a slightly higher cost (US$6.8). The ICER was US$1,356.2 per QALY gained. In probabilistic sensitivity analysis, there was an 82.7% probability that genotype-guided dosing was dominant over standard dosing, and a 99.8% probability that it was cost-effective at a willingness-to-pay threshold of US$50,000 per QALY gained. Conclusions: Compared with only standard warfarin therapy, genotype-guided warfarin dosing was cost-effective in MHVR patients under the fee-for-service insurance system.
Transition Study of Biosimilar Infliximab in Patients with Inflammatory Bowel Disease N. Boone1; L. Lui2; M. Romberg2; L. Duijsens2; H. van der Kuy1; R. Janknegt1; and A. van Bodegraven1 1 Zuyderland Medical Centre, Sittard, The Netherlands; and 2 VU University Medical Center, Amsterdam, The Netherlands Background: The introduction of biosimilars reduces costs. EMA’s biosimilar approval process is focused on preclinical similarity evidence and will not be sufficient to gain full trust in the medical field. The principle of “first do no harm” is challenged in a financially driven transition to biosimilar. A clinical infrastructure that facilitates the registration of efficacy and safety improves treatment insight. Methods: The infliximab biosimilar (BS-IFX) implementation started with a business case to facilitate collection of outcomes. Morbus Crohn (MC) and Colitis Ulcerosa (CU) patients on IFX were converted to BS-IFX and followed during 52 weeks. Quality of life (QoL) score, CRP, fecal-calprotectin, IFX neutralizing antibodies (NABs), IFX trough levels and disease activity measures were assessed on treatment visits 1, 2, 4 and 7. The protocol was reviewed by the local medical ethics review committee. Results: A group of 65 (24/41 CU/MC) patients enrolled the project after informed consent. Eight participating patients ceased BS-IFX therapy. Four patients ceased therapy due to NABs formation (1/3; CU/MC) against originator IFX and later against BS-IFX, loss of response and or adverse drug effects (ADEs). A group of three (1/2; CU/MC) patients ceased BS-IFX therapy without NABs formation due to experienced loss of response and one MC patient because of infusion reactions on both IFX and BS-IFX. One CU patient had a diminished QoL and increased levels of fecal-calprotectin after three BS-IFX gifts. Two MC patients had atypical complaints about ineffectiveness without QoL, laboratory abnormalities or ADEs after two BS-IFX gifts. The complaints of these two patients (3%) could be attributed to nocebo-effects. No patient newly developed NABs on BS-IFX. Conclusions: Implementation of biosimilars in an observational study provides insight in outcomes. The clinical study-wise patient-counseling could be an explanation for the relative low nocebo-effect rate. Noceboeffect rate could be a benchmark for good clinical practice.
Does Patient Health Empowerment Go Hand in Hand with Privacy Empowerment? L. Pereira; D. García; S. Fernández; M.J. Bertran; and N. Riba Hospital Clínic of Barcelona, Spain Background: The 2016 WHO report shows a huge increase in health applications, and states that, in 2014, 100,000 health apps
e9
Clinical Therapeutics were available with 70% targeting fitness and well-being. Recently mobile health applications (mHealth) have played a key role in aiding patients to have greater control and management of their diseases by the use of these applications, receiving disease education, medication information, task notifications, and synchronisation of records with online databases to better control symptoms. Methods: We searched the Research Ethics Committee (REC) database using the following keywords: app, mobile, smartphone, mHealth and empowerment to identify approved mHealth studies at the Hospital Clínic of Barcelona. Results: The results show that around 16 mHealth studies have been submitted to the REC between 2008 and 2017. These studies are related to different clinical areas such as cardiology, neuroscience, HIV, hepatitis C and erectile dysfunction. Conclusions: 1. mHealth technological development will allow diagnoses to improve and face-to-face visits to be reduced, maintaining better communication between patients and physicians. 2. Nevertheless, this brings new challenges for the protection of patient rights: – New mobile and cloud technologies permit processing of personal health data on an unprecedented scale for investigation. – mHealth technology poses questions about how sponsors handle dissociated personal data that could be attributed to an individual by the use of additional information, for example the phone where the app is downloaded, or by transferring of such data to third countries outside of the European Union. 3. Guidelines have been established by the Ethics Committee, Hospital Clínic of Barcelona to ensure maintenance of data confidentiality in mHealth studies.
Pharmacogenetics of Chemotherapy Response in Osteosarcoma: A Genetic Variant in SLC7A8 is Associated with Progressive Disease M.J.H. Coenen1; H.I. Vos1; J.M. Groothuismink1; W.T.A. van der Graaf1; U. Flucke1; H.W.B. Schreuder1; M.M. Hagleitner1; H. Gelderblom2; T. van der Straaten2; E.S.J.M. de Bont3; L.C.M. Kremer4; J. Bras5; H. Caron4; R. Windsor6; J. Whelan6; A. Patiño-García7; A. González-Neira8; G. McCowage9; S. Nagabushan9; D. Catchpoole9; F.N. van Leeuwen1; H.-J. Guchelaar2; and D.M.W.M. te Loo1 1 Radboud University Medical Center, Nijmegen, The Netherlands; 2Leiden University Medical Center, Leiden, The Netherlands; 3University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; 4Emma Children’s Hospital/Academic Medical Center, Amsterdam, The Netherlands; 5Academic Medical Center, Amsterdam, The Netherlands; 6University College Hospital, London, United Kingdom; 7University Clinic of Navarra, Pamplona, Spain; 8 Spanish National Cancer Research Center, Madrid, Spain; and 9The Children’s Hospital at Westmead, Westmead, NSW, Australia Background: Despite (neo) adjuvant chemotherapy in primary osteosarcoma or first-line chemotherapy in patients presenting with metastatic disease, some patients progress already during first-line systemic treatment and have a very poor prognosis. Here we investigated whether patients with an inadequate response to treatment have a distinctive pharmacogenetic profile, by applying a large scale screening including 1,936 genetic markers in 231 drug metabolism and transporter genes.
e10
Methods: Germline DNA from 287 Dutch high-grade osteosarcoma patients treated with cisplatin and doxorubicin-based chemotherapy was genotyped using the DMET Plus array. Associations between genetic variants and progressive disease (primary tumor and/or metastasis growth or formation up to 3 months after end of adjuvant chemotherapy or first-line treatment in case of primary metastatic disease; and/or inadequacy to reach complete remission at the end of therapy for primary localized or primary metastatic osteosarcoma) were assessed using logistic regression models. Followed by validation in 146 patients from Spain and the United Kingdom and a second validation in 28 patients from Australia. The study was approved by the institutional review boards. All patients and/or parents provided written informed consent. Results: In multivariable association analyses of genetic variants and progressive disease, adjusted for the presence of primary metastases, sex and age at diagnosis, 10 genetic variants in 6 genes were uniquely associated (P< 0.05) with progressive disease. Of these, SLC7A8 rs1884545 was independently validated, and showed increased significance in meta-analysis of all cohorts combined (OR 0.22 [0.07-0.63], P= 0.005). Three other variants, CYP8B1 rs6771233, SLC22A2 rs316003, and SLC22A5 rs274548 were also significantly associated in meta-analysis of all cohorts. Conclusions: We have identified genetic variants specifically associated with an inadequate drug response, defined as progressive disease, in osteosarcoma patients. This analysis represents the first step towards identifying patients for whom chemotherapeutic treatment is ineffective and should be further explored in additional cohorts.
Factors Associated with Vancomycin Concentration Variability in Routine Clinical Care K. Zagorodnikova; M. Kostitcyna; and A. Murzina North-Western State Medical University n.a. I.I.Mechnikov, Saint Petersburg, Russia Background: Vancomycin is still the first choice for prevention and treatment of infections caused by methicillin resistant Staphyllococcus aureus and Enterococci. It is widely accepted that its trough concentrations (VTC) are predictive of the therapeutics and adverse effects. There are many nomograms and protocols available for vancomycin dosing, and still concentrations are widely variable. We were aiming to study factors clinically relevant for VTC variability in a naturalistic study. Methods: All patients with clinical indications for vancomycin were recruited for the study. VTC were measured after achievement of the stationary level. Clinical and demographic parameters were registered and verified based on routine medical records: glomerular filtration rate (GFR) (Cockroft-Gault formula), age, weight, gender, co-medication with NSAIDs, inotropic medications, diuretics, infusion volume, APACHE-II score, additional body compartments (drainages, ascites etc), type of the wards (ICU/non-ICU). VTC were measured using HPLC-UV. Results: A total of 101 VTC from 68 patients were evaluated – all measurements were independent on each other, and related to different episodes of vancomycin use. After thorough check for correspondence of the dosing regimen to the dosing instruction based on GFR only 56 measurements were eligible for further analysis. VTC varied from 2 to 15 (mean 6±3) µg/ml. GFR and ICU treatment were the only factors responsible for 15% of the VTC variability in the linear regression model (P< 0.05). In patients with GFR above 80 ml/min VTC variability was still explained by GFR and use of loop diuretics (P< 0.01). VTC in patients in ICU correlated with the NSAIDs use (R 0.5; P< 0.05); this parameter, however, did not add to the prediction of VTC.
Volume 39 Number 8S
Cost-Effectiveness of Genotype-Guided Warfarin Dosing in the Patients with Mechanical Heart Valve Replacement Under Fee-For-Service System D.-J. Kim1; H.-S. Kim1,2; M.K. Oh1; E.-Y. Kim1,2; and J.-G. Shin1,2 Inje University College of Medicine, Busan, South Korea; and 2 Inje University Busan Paik Hospital, Busan, South Korea Background: Although studies assessing the cost-effectiveness of genotype-guided warfarin dosing for the management of atrial fibrillation and venous thromboembolism have been reported, no publications have addressed genotype-guided warfarin therapy in mechanical heart valve replacement (MHVR) patients or genotype-guided warfarin therapy under the fee-for-service insurance system. The aim of this study was to evaluate the cost-effectiveness of genotype-guided warfarin dosing in patients with MHVR under the fee-for-service system from the Korea healthcare sector perspective. Methods: A decision-analytic Markov model was developed to evaluate the cost-effectiveness of genotype-guided warfarin dosing compared to standard dosing. Estimates of clinical adverse event rates
1
August 2017
and health state utilities were derived from the published literature. The outcome measure was the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were performed to explore the range of plausible results. Results: In a base-case analysis, genotype-guided warfarin dosing was associated with marginally higher QALYs compared to standard warfarin dosing (6.088 vs. 6.083, respectively), at a slightly higher cost (US$6.8). The ICER was US$1,356.2 per QALY gained. In probabilistic sensitivity analysis, there was an 82.7% probability that genotype-guided dosing was dominant over standard dosing, and a 99.8% probability that it was cost-effective at a willingness-to-pay threshold of US$50,000 per QALY gained. Conclusions: Compared with only standard warfarin therapy, genotype-guided warfarin dosing was cost-effective in MHVR patients under the fee-for-service insurance system.
Transition Study of Biosimilar Infliximab in Patients with Inflammatory Bowel Disease N. Boone1; L. Lui2; M. Romberg2; L. Duijsens2; H. van der Kuy1; R. Janknegt1; and A. van Bodegraven1 1 Zuyderland Medical Centre, Sittard, The Netherlands; and 2 VU University Medical Center, Amsterdam, The Netherlands Background: The introduction of biosimilars reduces costs. EMA’s biosimilar approval process is focused on preclinical similarity evidence and will not be sufficient to gain full trust in the medical field. The principle of “first do no harm” is challenged in a financially driven transition to biosimilar. A clinical infrastructure that facilitates the registration of efficacy and safety improves treatment insight. Methods: The infliximab biosimilar (BS-IFX) implementation started with a business case to facilitate collection of outcomes. Morbus Crohn (MC) and Colitis Ulcerosa (CU) patients on IFX were converted to BS-IFX and followed during 52 weeks. Quality of life (QoL) score, CRP, fecal-calprotectin, IFX neutralizing antibodies (NABs), IFX trough levels and disease activity measures were assessed on treatment visits 1, 2, 4 and 7. The protocol was reviewed by the local medical ethics review committee. Results: A group of 65 (24/41 CU/MC) patients enrolled the project after informed consent. Eight participating patients ceased BS-IFX therapy. Four patients ceased therapy due to NABs formation (1/3; CU/MC) against originator IFX and later against BS-IFX, loss of response and or adverse drug effects (ADEs). A group of three (1/2; CU/MC) patients ceased BS-IFX therapy without NABs formation due to experienced loss of response and one MC patient because of infusion reactions on both IFX and BS-IFX. One CU patient had a diminished QoL and increased levels of fecal-calprotectin after three BS-IFX gifts. Two MC patients had atypical complaints about ineffectiveness without QoL, laboratory abnormalities or ADEs after two BS-IFX gifts. The complaints of these two patients (3%) could be attributed to nocebo-effects. No patient newly developed NABs on BS-IFX. Conclusions: Implementation of biosimilars in an observational study provides insight in outcomes. The clinical study-wise patient-counseling could be an explanation for the relative low nocebo-effect rate. Noceboeffect rate could be a benchmark for good clinical practice.
Does Patient Health Empowerment Go Hand in Hand with Privacy Empowerment? L. Pereira; D. García; S. Fernández; M.J. Bertran; and N. Riba Hospital Clínic of Barcelona, Spain Background: The 2016 WHO report shows a huge increase in health applications, and states that, in 2014, 100,000 health apps
e9
Clinical Therapeutics were available with 70% targeting fitness and well-being. Recently mobile health applications (mHealth) have played a key role in aiding patients to have greater control and management of their diseases by the use of these applications, receiving disease education, medication information, task notifications, and synchronisation of records with online databases to better control symptoms. Methods: We searched the Research Ethics Committee (REC) database using the following keywords: app, mobile, smartphone, mHealth and empowerment to identify approved mHealth studies at the Hospital Clínic of Barcelona. Results: The results show that around 16 mHealth studies have been submitted to the REC between 2008 and 2017. These studies are related to different clinical areas such as cardiology, neuroscience, HIV, hepatitis C and erectile dysfunction. Conclusions: 1. mHealth technological development will allow diagnoses to improve and face-to-face visits to be reduced, maintaining better communication between patients and physicians. 2. Nevertheless, this brings new challenges for the protection of patient rights: – New mobile and cloud technologies permit processing of personal health data on an unprecedented scale for investigation. – mHealth technology poses questions about how sponsors handle dissociated personal data that could be attributed to an individual by the use of additional information, for example the phone where the app is downloaded, or by transferring of such data to third countries outside of the European Union. 3. Guidelines have been established by the Ethics Committee, Hospital Clínic of Barcelona to ensure maintenance of data confidentiality in mHealth studies.
Pharmacogenetics of Chemotherapy Response in Osteosarcoma: A Genetic Variant in SLC7A8 is Associated with Progressive Disease M.J.H. Coenen1; H.I. Vos1; J.M. Groothuismink1; W.T.A. van der Graaf1; U. Flucke1; H.W.B. Schreuder1; M.M. Hagleitner1; H. Gelderblom2; T. van der Straaten2; E.S.J.M. de Bont3; L.C.M. Kremer4; J. Bras5; H. Caron4; R. Windsor6; J. Whelan6; A. Patiño-García7; A. González-Neira8; G. McCowage9; S. Nagabushan9; D. Catchpoole9; F.N. van Leeuwen1; H.-J. Guchelaar2; and D.M.W.M. te Loo1 1 Radboud University Medical Center, Nijmegen, The Netherlands; 2Leiden University Medical Center, Leiden, The Netherlands; 3University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; 4Emma Children’s Hospital/Academic Medical Center, Amsterdam, The Netherlands; 5Academic Medical Center, Amsterdam, The Netherlands; 6University College Hospital, London, United Kingdom; 7University Clinic of Navarra, Pamplona, Spain; 8 Spanish National Cancer Research Center, Madrid, Spain; and 9The Children’s Hospital at Westmead, Westmead, NSW, Australia Background: Despite (neo) adjuvant chemotherapy in primary osteosarcoma or first-line chemotherapy in patients presenting with metastatic disease, some patients progress already during first-line systemic treatment and have a very poor prognosis. Here we investigated whether patients with an inadequate response to treatment have a distinctive pharmacogenetic profile, by applying a large scale screening including 1,936 genetic markers in 231 drug metabolism and transporter genes.
e10
Methods: Germline DNA from 287 Dutch high-grade osteosarcoma patients treated with cisplatin and doxorubicin-based chemotherapy was genotyped using the DMET Plus array. Associations between genetic variants and progressive disease (primary tumor and/or metastasis growth or formation up to 3 months after end of adjuvant chemotherapy or first-line treatment in case of primary metastatic disease; and/or inadequacy to reach complete remission at the end of therapy for primary localized or primary metastatic osteosarcoma) were assessed using logistic regression models. Followed by validation in 146 patients from Spain and the United Kingdom and a second validation in 28 patients from Australia. The study was approved by the institutional review boards. All patients and/or parents provided written informed consent. Results: In multivariable association analyses of genetic variants and progressive disease, adjusted for the presence of primary metastases, sex and age at diagnosis, 10 genetic variants in 6 genes were uniquely associated (P< 0.05) with progressive disease. Of these, SLC7A8 rs1884545 was independently validated, and showed increased significance in meta-analysis of all cohorts combined (OR 0.22 [0.07-0.63], P= 0.005). Three other variants, CYP8B1 rs6771233, SLC22A2 rs316003, and SLC22A5 rs274548 were also significantly associated in meta-analysis of all cohorts. Conclusions: We have identified genetic variants specifically associated with an inadequate drug response, defined as progressive disease, in osteosarcoma patients. This analysis represents the first step towards identifying patients for whom chemotherapeutic treatment is ineffective and should be further explored in additional cohorts.
Factors Associated with Vancomycin Concentration Variability in Routine Clinical Care K. Zagorodnikova; M. Kostitcyna; and A. Murzina North-Western State Medical University n.a. I.I.Mechnikov, Saint Petersburg, Russia Background: Vancomycin is still the first choice for prevention and treatment of infections caused by methicillin resistant Staphyllococcus aureus and Enterococci. It is widely accepted that its trough concentrations (VTC) are predictive of the therapeutics and adverse effects. There are many nomograms and protocols available for vancomycin dosing, and still concentrations are widely variable. We were aiming to study factors clinically relevant for VTC variability in a naturalistic study. Methods: All patients with clinical indications for vancomycin were recruited for the study. VTC were measured after achievement of the stationary level. Clinical and demographic parameters were registered and verified based on routine medical records: glomerular filtration rate (GFR) (Cockroft-Gault formula), age, weight, gender, co-medication with NSAIDs, inotropic medications, diuretics, infusion volume, APACHE-II score, additional body compartments (drainages, ascites etc), type of the wards (ICU/non-ICU). VTC were measured using HPLC-UV. Results: A total of 101 VTC from 68 patients were evaluated – all measurements were independent on each other, and related to different episodes of vancomycin use. After thorough check for correspondence of the dosing regimen to the dosing instruction based on GFR only 56 measurements were eligible for further analysis. VTC varied from 2 to 15 (mean 6±3) µg/ml. GFR and ICU treatment were the only factors responsible for 15% of the VTC variability in the linear regression model (P< 0.05). In patients with GFR above 80 ml/min VTC variability was still explained by GFR and use of loop diuretics (P< 0.01). VTC in patients in ICU correlated with the NSAIDs use (R 0.5; P< 0.05); this parameter, however, did not add to the prediction of VTC.
Volume 39 Number 8S