Many reform efforts in health systems fall short because the use of research evidence to inform policy remains scarce. In Lebanon, one in four adults suffers from a mental illness, yet access to mental healthcare services in primary healthcare (PHC) settings is limited. Using an “integrated” knowledge framework to link research to action, this study examines the process of influencing the mental health agenda in Lebanon through the application of Knowledge Translation (KT) tools and the use of a KT Platform (KTP) as an intermediary between researchers and policymakers.This study employed the following KT tools: 1) development of a policy brief to address the lack of access to mental health services in PHC centres, 2) semi-structured interviews with 10 policymakers and key informants, 3) convening of a national policy dialogue, 4) evaluation of the policy brief and dialogue, and 5) a post-dialogue survey.Findings from the key informant interviews and a comprehensive synthesis of evidence were used to develop a policy brief which defined the problem and presented three elements of a policy approach to address it. This policy brief was circulated to 24 participants prior to the dialogue to inform the discussion. The policy dialogue validated the evidence synthesized in the brief, whereby integrating mental health into PHC services was the element most supported by evidence as well as participants. The post-dialogue survey showed that, in the following 6 months, several implementation steps were taken by stakeholders, including establishing national taskforce, training PHC staff, and updating the national essential drug list to include psychiatric medications. Relationships among policymakers, researchers, and stakeholders were strengthened as they conducted their own workshops and meetings after the dialogue to further discuss implementation, and their awareness about and demand for KT tools increased.This case study showed that the use of KT tools in Lebanon to help generate evidence-informed programs is promising. This experience provided insights into the most helpful features of the tools. The role of the KTP in engaging stakeholders, particularly policymakers, prior to the dialogue and linking them with researchers was vital in securing their support for the KT process and uptake of the research evidence.The online version of this article (doi:10.1186/s12961-015-0018-7) contains supplementary material, which is available to authorized users. Health systems worldwide often fail to use evidence optimally in their policymaking processes, creating a gap between knowledge and actual practice . RecentlKnowledge translation (KT) has emerged as a means for closing the gap between knowledge and practice. Straus et al.  formallyAs a result, knowledge translation platforms (KTPs) have been established in several LMICs . KTPs foA policy brief brings together global research evidence (from systematic reviews) and context-specific knowledge to inform deliberations about health policies and programs . Policy Nevertheless, it has not yet been determined how design and content features affect the usefulness of these KT tools . Only a Lavis et al.  propose This study seeks to gain a better understanding of the influence of KT tools and aims to inform initiatives towards promoting evidence-informed policymaking by taking mental health as a case study. It examines the process of influencing the mental health agenda in Lebanon through the application of KT tools and the use of a KTP as a first-of-its-kind initiative in Lebanon and the region.Mental disorders are a leading direct cause of disease burden worldwide . In LebaThe private sector provides most of the mental health services in Lebanon, and the MOPH contracts with private hospitals to pay for needy patients who require inpatient care. Three mental hospitals and five psychiatric units within general hospitals exist. The essential list of psychotropic medications includes antipsychotics, anxiolytics, mood stabilizers, and antiepileptics, which are supplied by the MOPH to PHC centres for free. Lebanon does not have enough psychiatrists , with the majority of those working in private practices or for-profit institutes. Two-thirds of other psychosocial professionals  work in the public sector according to the WHO AIMS Report of 2010 ; financiPrior to 2014, a dedicated mental health program did not exist within the MOPH, despite the eagerness of the ministry to be more active in this area. Initial efforts at training non-specialized PHC staff first began in 2008 by the International Medical Corps but were discontinued due to several challenges , and in In September 2013, the K2P Center partnered with the MOPH and identified mental health as a top health policy priority through a priority-setting exercise that the K2P Center aims to conduct on a regular basis. In parallel, the MOPH had been preparing a National Mental Health Program, which was officially launched later in April 2014. The integration of mental health into PHC was one of the program’s key priorities.The Kingdon model proposes that the public policy process includes multiple components flowing in different streams; problems, policies (solutions), and political will. When these streams intersect, a window of opportunity opens up and policymakers decide to act . This isThis study employed the following KT tools: 1) priority-setting, 2) development of a policy brief to address the mental health problem, 3) semi-structured interviews with policymakers and key informants, 4) convening of a national policy dialogue, 5) evaluation of the policy brief and policy dialogue, and 6) post-dialogue survey , indicators of the burden of mental illnesses, and relevant legislations and developments in the field of mental health in Lebanon in recent years. A search limited to documents published from the year 1996 to 2014 was conducted in MEDLINE, The Cochrane Library, and Google Scholar to retrieve relevant articles. The following keywords were used: mental health, mental health services, psychiatry-y/ic, psychology-y/ic, mental disorders, mental illness, Middle East, and Lebanon. WHO reports, including the WHO Mental Health Atlas , were alThe second step in the search strategy was performed to gather information on the different elements of the policy approach to address the problem. A search for relevant systematic reviews was conducted per element using the following databases: Health Systems Evidence, Cochrane Database of Systematic Reviews, The Cochrane Library, and SUPPORT. When systematic reviews were not available, single studies were retrieved from MEDLINE. The quality of systematic reviews was assessed using the AMSTAR scale, and the journal rankings for single studies were determined according to ISI Web of Knowledge. The details of the search strategies are presented in an additional file .The policy brief was then prepared by synthesizing the best available evidence about the problem and viable solutions through the comprehensive literature review. The gathered evidence was contextualized according to the health system of Lebanon using input gathered from context experts and policymakers throughout the process of drafting the brief. The policy brief was then used to inform deliberations of a national policy dialogue. It was circulated to dialogue participants prior to the dialogue to serve as the starting point for off-the-record deliberations.A K2P Litmus Test, adapted from the McMaster Health Forum , was perThe sampling frame included stakeholders in mental health from different disciplines: policymakers, researchers in mental health and public health, healthcare providers including mental health specialists, professional associations, civil society organizations, PHC representatives, and public and private insurers. A total of 12 informants were identified and targeted; out of these, 10 agreed to participate  they would bring to the dialogue unique views and experience to bear on the issue and learn from the research evidence and from others’ views and experience, and 2) after the dialogue they would champion within their respective institutions the actions that would address the challenge creatively. The dialogue ensured a fair representation among policymakers, civil society organizations, PHC representatives, researchers, healthcare providers including mental health specialists, and representatives of the National Social Security Fund (insurer) and International Health Organizations  were produced in both English and Arabic.The policy brief defined the overall problem as the limited access of a large proportion of individuals suffering from mental health problems and their families to mental healthcare services in PHC settings in Lebanon. The current health system arrangements do not ensure equitable access to high quality mental health services.From the perspective of service delivery, the only way to access mental healthcare in the public sector is through psychiatric institutions , and thiFrom a financing perspective, coverage of mental health services in Lebanon is extremely low as the primary source of financing for mental health is out-of-pocket payments. There are disparities in the coverage of public funding mechanisms for mental health services, and private insurance and mutual funds explicitly exclude these services from their policies . The depDuring the policy dialogue, participants confirmed the underlying factors forwarded in the policy brief. Deliberations around the problem definition, which was presented in the policy brief, consumed the largest amount of time. Participants agreed that there is a problem in the lack of trained healthcare professionals at PHC centres who can recognize mental health conditions and provide basic mental health services. However, a number of participants argued that the issue is not only the limited supply of services but also the limited demand for services, which is related to people’s poor awareness or knowledge about their mental health conditions.Participants reframed the problem as the limited knowledge of people suffering from mental health problems and their families about mental illness, as well as their limited access to mental healthcare services in PHC settings in Lebanon.Element 1: Integrate mental health into PHC service provision by developing an essential health services package to be a guaranteed minimum.Three elements of a comprehensive approach were presented in the policy brief; we refer to them as “elements” of a comprehensive approach rather than “options” because they are not mutually exclusive. This term was adapted from the McMaster Health Forum.WHO strongly recommends the integration of mental healthcare into general PHC services as the most viable way of ensuring that people have access to the mental healthcare they need . IntegraDeliberation about element 1 during the policy dialogue revealed that participants agreed with the need for a minimum service package. On choosing between the different models of collaborative care , participants noted that one model, such as task-shifting, is promising but would not be enough and that a combination of different models will most probably be needed in the context of Lebanon. PHC providers learn the general principles of care and the key actions such as establishing communication and building trust, conducting assessments, management of cases, referrals and follow ups for priority conditions. Participants recommended scaling up of the package for the most prevalent mental health conditions in Lebanon and using guidelines and protocols to standardize mental health practice in PHC settings. According to some participants, integrating screening as part of a horizontal program may induce over-diagnosing and thus is a potential harm of element 1.Element 2: Expand coverage of mental health services in the PHC setting, as well as coverage for specialist services for patients referred by PHC centres, through reimbursement by third party payers according to a capitation payment systemIt is important to note that integration does not reduce psychiatrists’ work, but rather changes the nature of their work to focus on more complex and severe psychiatric cases, while less complex cases can be managed by trained non-specialist health workers. This is what the evidence in the policy brief , 28 showUnder capitation, payment is made based on the number of patients to whom care is provided. Only one high-quality systematic review addressed payment mechanisms for mental health integrated into PHC, but it concluded that there is not yet sufficient evidence to determine which reimbursement system leads to better health outcomes or cost-effectiveness . AlthougElement 3: Recognize parity between mental health and physical health by developing and implementing appropriate legislation, including issuing the draft law for the licensing of psychologists, as well as the proposed Mental Health Act for the protection of psychiatric patients’ rightsDuring the deliberation about element 2, participants noted that the MOPH is already considering some form of capitation as a new model of financing PHC services in general, and not only mental health services. Issues raised by participants included the following: the need to take the patient’s perspective into consideration regarding capitation and the need for non-financial incentives for providers. Such incentives could include research opportunities for academicians, the privilege of being part of a national and international initiative, or in a material form such as the MOPH helping providers secure their Continuing Medical Education through the Order of Physicians. Another issue raised was the need to engage community stakeholders in the catchment area of the PHC centre, who could themselves participate in the funding of the centre’s mental health services.Although no systematic reviews were identified about policies related to integration of mental health into PHC, the search identified compelling evidence from numerous single studies on enacting mental health legislation. One of the most important benefits identified by several high-quality studies was that enacting national mental health-related policies resulted in a decline in suicide and self-harm rates.During the deliberations about this element, participants discussed the status of the Mental Health Act at the time of the dialogue. The political situation had been impeding the progress of the draft law, as it was still pending due to the idleness of the parliament and shortage of quorum. The Act was yet to be reviewed by the parliamentary committee and it focused on the following areas: protection of the patient, regulating the work of the psychiatrist, involuntary hospital admissions, freedom of the patient to select the kind of treatment within the hospital and to get a second medical opinion, the role of the government in treatment and follow-up after discharge, and setting procedures for the use of electroconvulsive therapy and physical restraints. Participants recognized that there might be an opportunity to lobby for this Act through patient advocacy initiatives.Nine out of 24 participants completed the policy brief evaluation survey, despite repeated attempts to administer the survey. The low response rate can be attributed to the participants’ busy schedules and time limitations. Average scores on all items were positive, ranging between 6 and 7. The results of the evaluation of the policy dialogue also yielded favourable results, whereby 9 out of 24 participants responded to the survey and average scores on all items were high, ranging also between 6 and 7. Results on the evaluation of the policy brief and policy dialogue are presented in Additional file The specific aspects of the policy dialogue that were found most helpful by participants were the graded-entry format that the brief employed , the fact that the brief described different features of the problem and three elements of an approach for addressing it, and that the brief described what is known, based on synthesized research evidence, about each of the three elements and what the gaps were. Participants also found helpful that the brief described key implementation considerations and took quality considerations as well as local applicability considerations into account when discussing the research evidence.As for the beneficial aspects of the policy dialogue, participants found most helpful that the dialogue was informed by a pre-circulated policy brief, and that it engaged a facilitator to assist with the deliberations. Other aspects deemed helpful were the fact that the dialogue brought together many parties who could be involved in or affected by future decisions related to the issue, and that it allowed for frank and off-the-record deliberations.Six key stakeholders were purposively selected from different agencies deemed as the most knowledgeable about the latest developments in the field of mental health in Lebanon, and four of them responded to the post-dialogue survey. The stakeholders represented the following agencies: WHO, MOPH, PHC, and mental healthcare providers and patient advocacy groups. The results of the survey revealed key actions undertaken by stakeholders following the dialogue. A mental health and psychosocial support taskforce was established to coordinate efforts across Lebanon. A WHO mhGAP adaptation workshop was held in June 2014 and, accordingly, an adaptation and translation of the WHO mhGAP training manual to fit the Lebanese context were conducted. In the same month, a meeting with the directors of PHC centres was held to secure their buy-in. This meeting was followed by initiating the mhGAP training-of-trainers and training in 45 out of 198 centres across Lebanon, along with the initiation of the Psychological First Aid training. In addition, the national drug list which includes mental health medications has been reviewed and updated, and performance indicators of the project were identified and integrated into the Ministry’s Health Information System.In parallel to those developments, other actions contributed to strengthening mental health in Lebanon. In July 2014, the MOPH secured a 20 million euro grant from the European Union to strengthen PHC services, including mental health, which will support the integration of mental health services into PHC. The national mental health strategy draft was reviewed. Two public debates of the draft mental health law were held in the summer of 2014 and modifications to the draft law were made based on evidence-informed practices and stakeholder input. The first national awareness campaign for suicide prevention was launched in September 2014. In addition, a national survey of Lebanese adults’ knowledge and attitudes towards mental illness was conducted between October and December 2014.Respondents also highlighted challenges they encountered in translating the elements that were discussed at the dialogue into action. This validated some of the challenges that were predicted in the policy brief based on previous international experiences with integration efforts. As cited in the policy brief, stakeholders faced opposition from psychiatrists to the integration of mental health services in PHC. In order to address this challenge, the roles of non-specialized staff and referral pathways were thoroughly discussed and clearly defined during the mhGAP adaptation workshop. Another expected barrier cited in the policy brief was the fear of specialists that non-specialized staff would not be sufficiently competent, and this was indeed faced in Lebanon. Accordingly, non-specialized staff members are being thoroughly trained under regular supervision for at least a year to make sure they are competent in assessing, diagnosing and managing some cases at PHC level, and referring cases that need specialized care. Finally, the policy brief cited opposition from PHC management as a barrier to integration efforts in many countries. To overcome this potential challenge, PHC managers were engaged at an early stage, i.e., before the trainings.The application of KT tools to tackle the problem of mental health and help generate evidence-informed policies and programs was a promising experience and the first of its kind in Lebanon and the region. This experience served as a demonstration of the KT process to Lebanese policymakers and proved to be a valuable means for bringing evidence into their hands.In this case study of mental health in Lebanon, a window of opportunity for influencing policymaking was identified. Within the priorities of its newly established National Mental Health Program, the MOPH had outlined what needs to be done, and the K2P Center played the role of providing the means through which to put the program into action; in other words, the how.The policy brief and policy dialogue helped inform policymaking at the government level. The policy dialogue, informed by a pre-circulated policy brief, has helped trigger or support multiple actions by stakeholders directly related to the integration of mental health into PHC, as well as actions aimed at strengthening other aspects of mental health in Lebanon (such as legislation and public awareness). Participants exhibited great momentum for mobilizing efforts to address the issue of mental health in Lebanon, as evident by the numerous steps taken in the 6 months that followed the dialogue. Participants also pointed out that the policy dialogue was an important opportunity for a large and diverse group to deliberate about the problem and its elements. A similar finding was reported in a study published by Moat et al.  in whichThis case study has shown that the use of KT tools strengthened the relationships among policymakers, researchers and stakeholders; different stakeholders continued the discussion that began at the policy dialogue through follow-up meetings and workshops that they conducted by themselves to delve further into implementation issues. The use of KT tools also increased their awareness about the importance of evidence-informed policymaking initiatives. This was translated into an increased demand for KT products by policymakers , and these findings are consistent with the outcomes reported by a study on 10 KTPs in different LMICs . After tAn important observation was that the framing of the problem proved to be critical. The key informant interviews and the policy dialogue helped in refining the framing of the problem. The policy dialogue also served to validate the evidence synthesized in the policy brief, whereby element 1 of the policy approach for addressing the problem was the most supported by evidence as well as dialogue participants. Here, it is interesting to point out that the participants’ choice of the element to pursue might not have been influenced only by the strength of the evidence supporting it, but also by the feasibility of its application in the context of Lebanon. Specifically, participants may have steered away from element 3, for example, because political factors in Lebanon were identified as a barrier that had been hindering the enactment of mental health legislation for years. The policy dialogue was instrumental in contextualizing the elements. This further emphasizes the importance of taking local context into consideration when discussing evidence and deciding on options to pursue. Previous studies have shown that the uptake of evidence by policymakers and its usefulness in supporting evidence-informed health policies is influenced by contextual factors, such as the institutions, interests, and values in the local context , 32.Follow-up after the dialogue, which in this case study was done through disseminating a policy dialogue summary and conducting a post-dialogue survey, is extremely important. In fact, related studies have reported that follow-up activities can help continue building the capacity of stakeholders to address the policy issue. Such activities include disseminating dialogue summaries, providing customized debriefing to specific stakeholders on the implications of the dialogue, or offering a year-long service of providing newly published evidence including systematic reviews , 33.There are several lessons learned from this KT experience. One lesson was that working within an “integrated” knowledge model was absolutely essential, whereby stakeholders were engaged from the very beginning and the KTP helped establish a partnership between researchers and policymakers. It was observed by the researchers that engaging key stakeholders early on through the K2P Litmus Test played an important role in securing their buy-in; such politics were just as important and time-consuming as writing the policy brief itself. This finding is consistent with the experience of other KTPs in LMICs [This experience helped provide insight on the most helpful aspects of the policy brief and policy dialogue. A study on the use of KT tools in six different LMICs found that every key feature of the evidence briefs and deliberative dialogues was viewed favourably by most respondents, regardless of the countries in which they were used or the issues they addressed . This waOne of the most helpful features of the policy dialogue reported by participants was that it engaged a skilled facilitator to assist with the deliberations. Similar findings have been reported in a study on KTPs in LMICs, which revealed that skilled human resources were a key component that helped KTPs engage in deliberative processes . AnotherAs positive as this experience of using KT tools for supporting evidence-informed policymaking has been, the K2P Core Team has observed that these tools might not be enough on their own to push health policy agenda in Lebanon. Taking mental health as an example, it was clear that for such a topic to be properly tackled, attitudes and perceptions need to be addressed not only at the policymakers’ level but also within the general public. Stakeholders at the policy dialogues stressed the importance of raising public awareness about mental health to complement the value added by KT tools. To arrive at healthcare system arrangements that guarantee proper provision of psychiatric and psychological services, the stigma of seeking professional mental healthcare needs to be tackled as well as people’s recognition of the signs and symptoms of common mental disorders.A limitation worth stating is the low response rate to the policy brief and dialogue evaluations, whereby only nine out of 24 participants responded to the questionnaires, despite repeated attempts to administer the survey. This can be attributed to the participants’ busy schedules and to the time constraints at the dialogue. Therefore, it is advisable to allocate around 10 minutes of a policy dialogue’s agenda specifically for participants to complete the evaluation surveys. Nevertheless, six participants provided positive feedback about the KT experience in a 3-min videotaped interview immediately after the dialogue.It is also important to caution that this study does not claim any cause–effect relationship stemming from the KTP process. Other factors may have contributed to the positive changes that followed, such as the clear recognition and interest of the MOPH in promoting mental health and the efforts made in previous years by different researchers and civil society groups to advance mental health in the country.The 6-month period between the dialogue and the post-dialogue survey was appropriate for examining short term developments following the KTP activities, but a longer period might be needed to capture further changes that might have materialized. An additional limitation is the absence of service users or their representatives from the Litmus Test stakeholder groups; this was remedied by including a patient advocacy group at the dialogue. Nevertheless, it may be worthy, in future KTP initiatives, to consult patients through focus groups designed specifically for patients allowing them to voice their true opinions and concerns.This study has demonstrated how the use of KT tools in Lebanon played a key role in helping mental health move forward on the policy agenda. Mental illness poses a significant burden on the Lebanese community, and yet, access to mental health services in PHC settings remains inadequate and inequitable. This problem was highlighted and a policy approach was presented and discussed by a multidisciplinary group of stakeholders. Moving forward, more work needs to be done on measuring not only the outcomes, but the impact of implementing evidence-informed policies using KT . Integrating monitoring and evaluation components of KT from the start allows us to measure whether and how research evidence was used in the policy, and whether the policy achieved its intended outcome and health impact. Strengthening the research base on the impacts of KT in improving health outcomes would solidify the argument for promoting evidence-informed health policies.


Background: Joint contractures are common problems in frail older people in nursing homes. Irrespective of the exact extent of older individuals in geriatric care settings living with joint contractures, they appear to be a relevant problem. Also, the new emphasis on the syndrome of joint contractures, e. g. by the German statutory long term care insurance, led to an increase in assessment and documentation efforts and preventive interventions in clinical care. However, more attention should be paid to the actual situation of older individuals in nursing homes with prevalent joint contractures, particularly their experience of related activity limitations and participation restrictions. Thus, the aim of this study is 1) to develop a tailored intervention to improve functioning, and especially participation and quality of life in older residents with joint contractures in nursing homes and 2) to test the feasibility of the intervention accompanied by a rigorous process evaluation.Methods: The complex intervention, which will be developed in this project follows the UK Medical Research Council (MRC) framework and integrates the perspectives of all potentially relevant user groups, from the affected individuals to clinicians and researchers. The development process will comprise a systematic literature review, reanalysis of existing data and the integration of the knowledge of the affected individuals and experts. The developed intervention including a comprehensive process evaluation will be pilot tested with residents with joint contractures in three nursing homes. Discussion: The projected study will provide a tailored intervention to improve functioning, participation and quality of life in older residents with joint contractures in nursing homes. With this focus, the intervention will support patient relevant outcomes. The pilot study including process evaluation will offer a first opportunity to indicate the size of the intervention’s effect and prepare further studies.  Joint contractures are associated with restrictions in full range of motion of any joint due to deformity, disuse, and pain. They are common problems of frail older people, particularly in nursing home residents , 2]. Ir. Ir2]. IPrevalence data on joint contractures are scarce and estimates vary widely, presumably due to different definitions and populations. Studies involving nursing home residents in the US report prevalence rates between 25%  and 80% Irrespective of the exact number of older individuals in geriatric care settings living with joint contractures, joint contractures appear to be a relevant problem and receive growing attention. For example, the German federal statutory long term care insurance system has defined the assessment of risk for joint contractures and the implementation of preventive measures as quality indicators in long-term nursing care , 12], , . This neAs proofs of effectiveness are missing for the primary and secondary preventive interventions that are part of the current standard of care in joint contractures, an alternative focus should be on interventions which do not merely address prevention or treatment of joint contractures but also focus on maintaining or enhancing participation and quality of life. Thus, more attention should be paid to the actual situation of older individuals in nursing homes with prevalent joint contractures, particularly their experience of related activity limitations and participation restrictions. To address this issue, we have recently developed a standard set based on the WHO’s International Classification of Functioning, Disability and Health (ICF)  to comprThe development of relevant, effective and feasible health care interventions is challenging, since changes in health care practice are rather complex than deterministic. To address these issues und to ensure the development of theoretically and empirically plausible, consumer-orientated and feasible interventions, the UK MRC framework was introduced to provide guidance on how to develop and evaluate complex interventions. It identifies the following four key elements of this potentially cyclical process: development, feasibility/piloting, implementation and evaluation. This study protocol focuses on the development and the feasibility/piloting phases. The development phase usually includes identification of the relevant evidence base, identification or development of a theory and modelling of the intervention process and the addressed outcomes. In the feasibility and piloting stage, the acceptability and feasibility of the developed intervention is carefully assessed. Also, recruitment procedures and recruitment and retention rates have to be evaluated. In addition, the basis for sample size calculations can be investigated in this phase , 21]. B. B21]. BAn overview of all applied methods and designs is given in Table 1 The study protocols of all empirical parts of the projects will be presented to the respective ethics committees of the Ludwig-Maximilians-Universität in Munich and the Martin-Luther-University in Halle-Wittenberg prior to the start of the respective part. Written informed consent from the participants or their legal guardians will be obtained prior to inclusion in the study.Aims: The aim of this systematic review is to identify the existing evidence regarding prevention and/or treatment of disability due to joint contractures which serves as basis for the intervention modelling. Methods: The systematic review will be carried out in electronic databases  and via hand searches. The process and results will be documented using an electronic database. The review will include randomized and non-randomized controlled trials on programs for prevention and/or treatment of disability due to acquired joint contractures. Target population are individuals in need for long term care of either type. Analysis: The critical appraisal will follow the Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0 , . I. IParticAnalysis: Since graphical models are susceptible to small changes in the data set leading to great changes in the result, we implement bootstrap aggregating (bagging) to stabilize the outcome of such a model and subsequently enhance accuracy ,  by byAnalysAims: To develop a preliminary list of intervention components, a structured two-day meeting with renowned national clinical experts will be held. Participants and design: The results of the systematic review, the potential intervention goals and the focus groups as well as the results of the qualitative interviews from our previous project  by byAnalysAim: The main objective of the pilot study is to estimate the effect size in order to plan the sample size for the main cluster-randomized trial. Participants and design: The pilot study will be designed as a cluster randomized controlled study to assess the feasibility of the developed intervention and its components. Target population for the pilot study will be residents with joint contractures in six nursing homes in the area of Munich, Halle and Witten. Presence of joint contractures will be evaluated by either physicians’ diagnosis or the diagnosis of a skilled staff nurse or physical therapist. There will be no other inclusion criteria. We will exclude residents with limited life expectancy due to advanced cancer or other diseases with poor prognosis according to the assessment by the nurse in charge. Each nursing home will be randomly assigned to the intervention group or to the control group. In line with suggestions of Billingham et al. ..AnalysisTo improve overall scientific quality, an external advisory board with clinicians and methodological experts will be established.This study protocol describes the development and piloting of a complex intervention that aims to improve the situation of older individuals with joint contractures in nursing homes. With the emphasis on participation and quality of life, this intervention will address a health outcome that is highly relevant to the affected individuals. This is particularly important since interventions aiming to improve the physical perspective of joint contractures (i.e. range of motion) seem to have limited effects , 16], , . Developing complex interventions is a challenging task . UnfortuThe authors declare that they have no competing interests.MM, EG and GM contributed to the conception of the study and applied for funding. MM, EG and GM conceived the study design. MM and HK drafted the manuscript. SS, AS, KB, GM, EG, GB, and RS critically revised the drafts and contributed to the final writing of the paper. EG and GM share the senior authorship. All authors read and approved the final manuscript. The project is funded by the German Federal Ministry of Education and Research (01GY1327A and 01GY1327B – JointConImprove).


Despite the indisputable mortality advantages of implantable cardioverter defibrillators (ICDs), no consensus exists regarding their impact on quality of life (QoL). This systematic review investigates differences in QoL between patients with ICDs and controls. We systematically searched the MEDLINE, EMBASE, Cochrane, Web of Science, and PsychINFO databases. Articles were included if they were published after the year 2000 and reported on original studies with a control group. Five randomized controlled trials with a total of 5,138 patients and 10 observational studies with a total of 1,513 patients met the inclusion criteria. Nine studies found comparable QoL for ICD recipients and patients in the control groups, three studies found an increased QoL for ICD patients, and three studies found a decreased QoL for ICD patients. The question of whether QoL relates to ICD therapy cannot be answered conclusively due to the heterogeneity of the existing studies. Lower QoL was apparent among patients with an ICD who experienced several device discharges. Medical staff should be particularly aware of the signs of both psychological and physical disorders in these patients. Further investigations on QoL in ICD patients are desirable, but ethical reasons restrict the conduct of randomized trials. Since the first implantation of an implantable cardioverter defibrillator (ICD) in a human being in 1980 –9. ConseBecause the implantation of an ICD is often a prophylactic therapy, not all individual patients who receive such a device will experience lifesaving shocks and derive a survival benefit from it. This fact and the divergent arguments supporting either a reduced or an increased QoL among patients with an ICD warrant an exploration of patients’ actual perceptions of their QoL following ICD implantation. A variety of cardiac patients exist who are alternately treated with an ICD and could potentially serve as a control group. We represent this variety in our systematic review to provide an extensive overview. The primary objective of our systematic review was to investigate whether the health-related QoL of patients with ICDs differs from that of patients who have received medical treatment and from that of patients who have undergone pacemaker implantation or received no intervention. If they were reported in the studies, we also considered ICD shocks or patients’ age as secondary objectives because they are linked to QoL.The methods used in our systematic review are based on the Cochrane Handbook for Systematic Reviews of Interventions . Table 1From the initial search results, we included studies in the review if they evaluated the influence of an ICD on QoL, were original studies, and were published in either German or English after the year 2000. Since 2000, all ICD devices have incorporated high-grade technology that is intended to reliably discriminate between supraventricular and ventricular rhythms . To be iCase studies, cost-effectiveness analyses, systematic reviews, comments, letters, and overview texts were excluded, as were studies without a clearly defined control group without ICD. To provide a broad overview, we did not further specify the type of comparison, though the comparison between single studies became more difficult as a consequence. Possible therapeutic alternatives included no intervention, pacemaker implantation, and medical treatment. We also did not include studies in the review that considered the effects of shocks or device recalls on QoL as their primary objective or studies on resynchronization therapy.Searches were conducted in all databases on January 13, 2014. Identified records were exported to EndNote X7 and filtered automatically for duplicates. The selection of relevant articles was supervised by a clinical cardiologist. The first level of selection included an independent screening of titles by two reviewers, a health economist and a mathematician. The reviewers’ relative distance from cardiology supported the neutral selection of articles via the application of the defined inclusion and exclusion criteria. The titles of the identified articles were jointly screened, and a decision regarding each article’s inclusion was reached following discussion and the achievement of consensus. The second step of screening entailed the consideration of the abstracts of the remaining articles in a manner similar to that of the first level of selection. The third step entailed full-text screening. The references of the resulting studies, as well as those of each of the systematic reviews identified via the abstract screening, were subsequently hand-searched by one reviewer for further relevant studies.One reviewer assessed the level of evidence of the studies that were included using the Oxford Centre for Evidence-Based Medicine Levels of Evidence . AdditioFor the aggregation of studies, one reviewer defined different subcategories of QoL  based on each of the applied questionnaires and their subscales. For each study, a thorough inspection of the questions contained in the respective questionnaires was conducted to determine which of the defined subcategories would be examined by a particular study.The selection process for the studies included in this review is illustrated in Figure The studies included in our review varied with respect to the control groups and inclusion and exclusion criteria, as well as the demographic characteristics of the study. For example, one study investigated QoL in children , and anoThe quality assessment revealed frequent methodological limitations, such as an insufficient description of the statistical analyses, the recruitment process, and the existence of missing data and their handling. Furthermore, the problem of multiple testing and confounding variables was often not incorporated into the statistical analyses.All five of the identified RCTs –23 and oPacemaker patients served as control subjects in five cross-sectional studies –31. Due Redhead et al.  comparedThe studies included in our review were arranged according to characteristics that contribute to QoL. These include physical and mental health, e.g., physical limitations, bodily pain, social functioning, anxiety, and depression.Table The cross-sectional study by Czosek et al.  and the All but two studies investigated whether a correlation exists between the perceived QoL of patients with an ICD and delivered shocks. Four cross-sectional studies and one cohort study did not observe any differences in health-related QoL between patients with an ICD who had or had not experienced a shock –29, 31. Two RCTs reported that QoL of ICD patients depended on the number of shocks received. Irvine et al.  and PassThree cross-sectional studies , 32, 33 In general, we could not ascertain a uniform trend regarding the QoL of patients who received an ICD. The majority of studies concluded that there was no difference between the ICD groups and the control groups. For the subgroup of patients who experience ICD shocks, the data suggest unchanged or poorer QoL compared to ICD patients without ICD discharge. A high number of shocks and the recency of shocks appear to correlate with reduced QoL. However, an underlying causality cannot be deduced from this correlation. It is possible that repeated shock experiences will influence a patient’s perception of his health in a negative way. It is also possible that sicker patients with poorer QoL are increasingly affected by shocks.Due to differences in control groups, study designs, and inclusion and exclusion criteria, there was limited comparability and heterogeneous methodological quality among the studies reviewed. The three studies that were assessed to be of high quality and to have a high level of evidence were the SCD-HeFT , the MADBecause several RCTs have demonstrated that ICDs exert a survival advantage over medical treatment –9, the aTwo additional limitations of the studies that assessed the relationship between ICD implantation and various outcomes are the impossibility of blinding and the definition of a suitable control group. Unblinded cardiologists do not ensure the equal treatment of patients who are receiving distinct therapies. Hence, there exists a high risk of bias. This is particularly important when assessing an outcome such as QoL, which is often influenced by a patient’s contact with medical staff. The selection of a control group for an ICD population often requires relatively large compromises. Patients with an implanted pacemaker, for instance, often differ in both their demographic and clinical characteristics. They are usually older than patients with an ICD and are more likely to be women.As a procedural limitation of the development of our review, the screening of titles as an initial selection step must be mentioned. This step is more prone to missing relevant articles than screening of abstracts. An additional issue is the inclusion of newer studies that were published only following the year 2000. In some cases, there existed a time lag of several years between the completion of the study and the publication of the results. Hence, there were studies that investigated patients much earlier than the publication date , 27. ConPrevious reviews and meta-analyses on QoL in ICD patients drew opposing conclusions. McCready et al.  concludeOur systematic review confirmed the trend observed by McCready et al.  and GroeThe value of pre- and post-implantation QoL comparisons appears to be limited. We expect an imminent implantation to strongly influence patients’ QoL and their psychological well-being in particular. QoL may decrease due to worries about the surgical operation or increase due to the expected improvement of state of health owing to the ICD. Therefore, we focused on the comparison between patients who received an ICD and a non-ICD control group in our systematic review.The heterogeneous results of the studies available for our review did not permit a definitive answer to the question of whether health-related QoL differs between patients with an ICD and respective controls. One may remain critical of whether patients with pacemakers or patients who have received medical treatment are representative as control patients. Lower QoL was apparent among ICD patients who experienced several device discharges. Medical staff should be particularly aware of psychological and physical effects in these patients. Future research on these open QoL questions is difficult because it is currently not ethical to randomize patients to ICD or control treatment.JT contributed to concept and design, data collection, screening of literature, summarizing and interpreting literature, drafting article, critical revision of the article, and approval of the article. KK contributed to concept and design, critical revision of the article, and approval of the article. MZ contributed to supervision of screening of literature, critical revision of the article, and approval of the article. SW contributed to critical revision of the article and approval of the article. TR contributed to concept and design, data collection, screening of literature, summarizing and interpreting literature, critical revision of the article, and approval of the article.Juliane Tomzik: none. Katharina C. Koltermann: consultancies as part-time manager for Boston Healthcare Associates, external scientific consulting services for Takeda, CGS Clinical Guideline Services, Keimzelle Medical Ventures, and Scenarium Group GmbH. Markus Zabel: consultancies, research and travel grants: Biotronik, Medtronic, Boston Scientific. Stefan N. Willich: none. Thomas Reinhold: received fees from ICD manufacturer Biotronik for external scientific consulting services.


Forecasting methods rarely addressed uncertainty. The objective of this project was to propose a methodology to perform pharmaceutical expenditure forecasting that integrates expected policy changes and uncertainty  Identification of all pharmaceuticals going off-patent and new branded medicinal products over a 5-year forecasting period in seven European Union (EU) Member States. 2) Development of a model to estimate direct and indirect impacts  on savings of generics and biosimilars. Inputs were originator sales value, patent expiry date, time to launch after marketing authorization, price discount, penetration rate, time to peak sales, and impact on brand price. 3) Development of a model for new drugs, which estimated sales progression in a competitive environment. Clinical expected benefits as well as commercial potential were assessed for each product by clinical experts. Inputs were development phase, marketing authorization dates, orphan condition, market size, and competitors. 4) Separate analysis of the budget impact of products going off-patent and new drugs according to several perspectives, distribution chains, and outcomes. 5) Addressing uncertainty surrounding estimations via deterministic and probabilistic sensitivity analysis.This methodology has proven to be effective by 1) identifying the main parameters impacting the variations in pharmaceutical expenditure forecasting across countries: generics discounts and penetration, brand price after patent loss, reimbursement rate, the penetration of biosimilars and discount price, distribution chains, and the time to reach peak sales for new drugs; 2) estimating the statistical distribution of the budget impact; and 3) testing different pricing and reimbursement policy decisions on health expenditures.This methodology was independent of historical data and appeared to be highly flexible and adapted to test robustness and provide probabilistic analysis to support policy decision making. With the economic crisis of 2008 and the substantial increase in public budget deficits, governments have implemented austerity plans to lower debt levels. The ever-growing pharmaceutical expenditure became a major target of healthcare cost-containment efforts, and several measures were implemented in European countries to contain public medicine expenditure. Common measures included price reductions; changes in the co-payments, in the Value-Added Tax rates on medicines, and in the distribution margins; as well as generics and biosimilars promotion , 2. NatiA review of the main existing models related to pharmaceutical expenditure forecasting showed an increase in health expenditures over the years. Indeed, using a Markov micro-simulation model based on a French patient database to measure the impact of ageing and chronic conditions on the evolution of future drugs expenditure from 2004 to 2029, Thiébaut et al. found that reimbursable drug expenditures will increase between 1.1 and 1.8% per year due to epidemiological and life expectancy changes . Connor Although these models allowed expenditure forecasting, they rarely addressed uncertainty and are therefore inappropriate in a fast-changing policy environment with difficult prediction of future policy landscape. This review of models also showed that there were no publications modeling the whole process of savings due to products going off-patent  and additional costs of new branded medicinal products at drug level.http://ec.europa.eu/health/healthcare/key_documents/index_en.htm).The objective of this project was to develop a methodology to forecast pharmaceutical expenditure while integrating expected policy changes and uncertainty in seven European Union (EU) Member States (MS) ) over a 5-year forecasted period (2012–2016). This project was performed for the European Commission  and new branded medicinal products in the selected EU MS were identified for the period 2010–2016. Only products that went off-patent or were approved in 2010 and 2011 were expected to impact the pharmaceutical budget on the forecasted period 2012–2016.Several sources of information were used to get an exhaustive list of products going off-patent and all new branded medicinal products as described below.Products going off-patent were identified through several sources of information, such as Datamonitor reports, the PharmaVitae database, the Medtrack database, patent databases , pharmaceutical company websites, press releases, investors’ reports, and the IMS database, as well as an in-house proprietary drug information database. For biosimilar drugs, exact patent expiration dates are generally hard to establish because of the lack of centralized listing of biological patents and the fact that expiration dates are proprietary information to the companies. Moreover, each product has formulation patents that are difficult to assess. Biological expirations over the forecasted period were therefore mainly extracted from the Generics and Biosimilars Initiative (GaBi) .New branded medicinal products were identified by cross-checking several databases such as European Medicines Agency (EMA) public information, Datamonitor reports, the PharmaVitae database, the Medtrack database, pharmaceutical company websites and press releases, investors’ reports, an in-house proprietary drug information database, and study registries such as clinicaltrials.gov.Drugs that could be approved or were approved via the EMA procedure, that is, drugs for the treatment of Human Immunodeficiency Virus, cancer, diabetes, neurodegenerative diseases, immune dysfunctions, and viral diseases; medicines derived from biotechnology processes; advanced-therapy medicines, orphan medicines; or medicine considered as a significant innovation or of interest of public health .Only the first approval of new entities was considered. Renewals, variations, or updates were excluded.Only products that had a positive phase IIb on the primary endpoint were taken into account, in order to minimize uncertainty and be consistent with the time window considered for this project. Orphan drugs with an ongoing phase II, which due to the orphan procedures could potentially reach the market during the forecasted period, were considered as being potential new drugs.In light of the development time required for new vaccines , vaccines were not considered to have a significant budget impact in the 5-year period of interest.New drugs were selected according to the following criteria:This model estimated a separate and combined effect of the direct and indirect impacts on savings from the genericization of the market for each year in the forecasted period based on the literature review, the local expert consultation, and the study board of experts’ insight. Inputs considered to assess the direct and indirect impacts of generic entry are presented in For this model, the sales evolution of generic and biosimilar products was assumed to be linear for the retail chain distribution until reaching peak sales, considering that the largest budget impact would happen after peak sales. Once the peak of sales was reached, it was assumed that sales would remain stable over time. For the hospital distribution chain, peak sales were assumed to be reached at day 1, as hospitals optimize their purchaser position through tenders.The direct impact on savings corresponded to the value extrapolated from the market share evolution of the generic or biosimilar drug versus the original branded drug.Sales value for 2011 of the original branded drug extracted from the IMS database, including hospital and retail sales as well as manufacturer and public sales.Date of the marketing authorization, assumed to be the same as the date of patent expiry of the original branded drug. Indeed, with the provisions of the EU regulatory system, it is not allowed to link marketing authorization to the patent status of the originator reference product .For generics and biosimilars distributed through the retail chain, the time to market after marketing authorization corresponded to the time delays of pricing and reimbursement status after marketing authorization. For biosimilars, time to uptake was also considered for the time to market. Indeed, low biosimilar uptakes are reported in Europe due to the reluctance of physicians to prescribe them and due to the fact that, unlike generics, they cannot be substituted.Generics and biosimilars distributed through the hospital chain were assumed to reach the market after marketing authorization without any delay.Time to market after marketing authorization.Price reduction of the generic or biosimilar drug versus the original branded drug.Generic or biosimilar drug penetration versus original off-patent branded drug in volume.Time to reach generic or biosimilar drug peak sales.Impact of generic or biosimilar drug entry on original branded drug price.Seven inputs were considered to calculate the direct impact:The market share within the same therapeutic class.The price reduction within the same therapeutic class.The life cycle management strategies.The augmentation of some market due to ageing.The assessment of the indirect impact of generic entry included:The model estimated the value of sales and progression of market share of new innovative medicines in a competitive environment and took into account the risk of failure regarding the development of the drug per therapeutic class using the results from a study conducted by DiMasi et al. .Development phase of the new drug.Potential marketing authorization dates.New drugs were looked at individually to assess their clinical potential and translate it into commercial potential. Five inputs were considered to calculate the potential impact of the new approved medicines :DevelopmStatus of the disease Total sales value in 2011 for each of the main therapeutic areas and total sales value in 2011 for the main competitorsPotential marketing authorization dates were based on Datamonitor reports, the PharmaVitae database, the Medtrack database, pharmaceutical companies websites, press releases, investors’ reports, and clinical trial registries such as clinicaltrials.gov. Dates were reviewed and validated by the study board of experts based on the available clinical trials performed, the initiation date of ongoing phase III trials, recruitment progress, the disease area, and the date of marketing authorization application filing to the EMA, if applicable. These rules were modulated based on the number of patients to be recruited, the evidence of the recruitment speed based on clinical trial registries when well updated, the trial sample size, and the disease area, as the speed of the running trial is not consistent across diseases.In the case of products used to treat rare diseases, peak sales were considered to be achieved over a year, due to the important unmet needs for therapies in these disease areas, the lack of alternative therapies in most cases, and the targeted prescribers who are well informed of any new treatment options. For other products, sales were considered to reach peak over a period of 3 years.Impact of the new drug based on a budget impact analysis to determine if the new drug would substantially impact the sales value of a given disease area.The sales of the new drug, in all countries with the exception of Germany, were assumed to impact the market 1 year after the date of marketing approval in the EU due to pricing and reimbursement policies. For Germany, the impact was assumed to be at market approval, as companies initiate sales based on a free pricing for the first year following the launch of new innovative drugs.The study board of experts reviewed evidence on either efficacy or safety improvements provided by the new drug over the available drugs in the same therapeutic area to determine if the new drug could have a significant budgetary impact. The board of experts took into account new attributes brought by the product from the perspective of the HTA in place for each country. A new drug should have added clinical value to be considered as impacting the sales of a therapeutic area. In principle, this meant that the generated sales of products with similar clinical value would only replace sales of existing products. This was consistent with actual regulations within EU countries. When assessing the potential clinical benefit of the new drugs on the forecasting period, the study board of experts considered the increase in pressure on pharmaceuticals to evidence additional clinical or economic benefits to achieve market access.French Health Authority (HAS) assessments were used whenever available for already approved drugs (2010–2011), and the budget impact was considered only for new medicines with the following Improvement of Medical Benefit  scores rated on a 5-level scale: ASMR I (major improvement), II (important improvement), and III (moderate improvement). Medicines with ASMR IV (minor improvement) and V (no improvement) were not considered to have an impact on budget. The HAS clinical perspective was complemented by Scottish Medicines Consortium (SMC) reviews to provide a perspective on the incremental cost-effectiveness.For new drugs that were not approved yet, clinical results of the phase II study were reviewed through related press releases, company websites, trial registries, conference abstracts, and analyst reports and used to assess the potential clinical benefit.The following new drugs were assumed not to have any budget impact: combinations of already approved products, unless there is a major added value in terms of efficacy or safety versus the combination of the active compounds taken separately; me-too drugs; and new formulations of approved products.Specific assumptions were adopted for the oncology area, and impact assessments were based on the overall survival. Products were considered as not assessable when the overall survival benefit was not available. The impact was then quantified by the study board of experts, case by case, based on the current prices of existing alternative treatments, the magnitude of overall survival, the severity of the condition, the existence of effective therapies, the market share of different products, and any relevant information specific to each case. New oncology drugs, as a result of their costliness, were assumed not to have an important development in lower income countries . A different methodology was implemented to estimate the penetration rate's evolution in these countries. Oncology drugs sales’ proportions were estimated in lower income countries with French sales in 2011 as a reference. The estimated proportion was considered as constant during the forecasted period.The manufacturer's perspective, by taking into account manufacturer ex-factory sales.Society’s perspective, by integrating all sales based on retail and hospital sales irrespective of reimbursement.The Healthcare public payer’s perspective, by applying the reimbursement rates in place in each EU MS to public sales.The budget impact of products going off-patent and the impact of new branded drugs were analyzed separately according to three perspectives:Several types of distribution chain Several outcomes One global rate for reimbursement rates: the decision was made to apply one global rate per country on total pharmaceutical expenditures based on the mean of co-payment levels in place in each country. This assumption appeared to be quite reasonable considering that the main pharmaceutical classes were represented in our model. As such, applying different levels of reimbursement rates was expected to lead to similar results as applying an average rate across the different therapeutic areas. Furthermore, reimbursement rates also depend on patient diseases, patient ages, the cost of medicine, and so on in most countries. We assumed that applying this reimbursement rate for all consumed medicine, including in hospitals, would not substantially affect the results of our model.These budget impacts were also analyzed separately according to the following :One globAgeing was taken into account directly in the input parameters of the model and indirectly for prevalence calculation purposes, using the evolution of the population structure (the average evolution from 2012 to 2016 derived from the 2012 ageing report) . These dPrevalence data were mainly extracted from Datamonitor epidemiology reports. When these were not available, various public sources were searched, including Medline and Embase and web sources , and prevalence for one country or global average prevalence for all countries was used as an estimate for other countries, taking into account ageing by using the evolution of the population structure (2012–2016) derived from the 2012 ageing report .The variability surrounding estimations was addressed in two ways: a deterministic one-way sensitivity analysis to identify drivers of the model outputs and a probabilistic sensitivity analysis to quantify uncertainty around the model outputs. The following parameters were included in the sensitivity analysis: the time to market after marketing authorization, time to reach peak of sales for new drugs (treating rare or non-rare diseases), price reduction of generic or biosimilar drugs, generic and biosimilar penetration, time to reach maximum of generic and biosimilar penetration, impact of generic and biosimilar drug entry on branded drug price, and reimbursement rate. Moreover, probabilistic sensitivity analysis specifically addressed the uncertainty surrounding the experts’ inputs related to the budget impact analysis of the new drugs.Additionally, in order to account for the uncertainty regarding the reimbursement rate applied for all medicine, including in hospitals, a specific scenario was developed in which the reimbursement rate was accounted only in the outpatient sector.Deterministic sensitivity analyses involve running the model for different values of model inputs, which are specified by the user, and comparing the obtained results. For this model, all parameters were increased and decreased by 30% of the original value, in order not to overweigh a parameter's variation compared to the others. This allowed us to see which parameter was a key driver of the model. The results of the deterministic one-way sensitivity analysis on the pharmaceutical net budget impact were presented per country as tornado diagrams, representing the range of variation of the pharmaceutical net budget impact for alternative values of several parameters.a priori) assumptions. For some values, the bound obtained was not realistic , in which case coherent bounds were used. The model was subsequently run 1,000 times, the aggregated results of each simulation for each country and each perspective were saved and plotted, and basic statistics were computed .With probabilistic sensitivity requiring specifying statistical distributions for all influential parameters surrounded with uncertainty, the model has to be run a large number of times , providing statistical distributions for model results. In this model, a uniform distribution was used for each parameter of the model. This allowed for each value between the bounds of the range to have the same probability to be generated, meaning that uncertainty was reflected without any .Scatterplots showing the spread of the ‘savings’ related to generics and ‘additional costs’ related to new branded medicinal products from simulations.Results of the probabilistic sensitivity analysis were presented as:Budget impact analysis showed that during the period of interest, all countries would experience a drug budget reduction, except Poland, which would experience an increase of +€41 million. Decrease in drug expenditure was the highest for the UK with −€9,367 million, followed by France with −€5,589 million, and farther behind by Germany with −€831 million and Greece with −€808 million, Portugal with −€243 million, and finally Hungary with −€84 million .Forecasting results are further described and discussed in a separate article, ‘EU pharmaceutical expenditure forecast ’.Three parameters had important impacts in the UK, France, and Hungary: price reduction of generics versus original branded drugs, penetration rate of generics via retail chain distribution, and reimbursement rate –6. OtherIn Germany, price reduction of generics versus original branded drugs and penetration rates of generics via retail chain distribution were the main impacting factors. The time to reach peak of sales for new drugs used to treat non-rare diseases was also an essential parameter .In Portugal and Poland, the model was much more sensitive to variations in input parameters  and 9. KThe most important parameters influencing the model, in Greece, were the impact of entry of the generics on the original branded drug price and the reimbursement rate, followed by the price reduction of generics versus original branded drugs through retail chain distribution .The analysis showed that, in all countries except Portugal and Poland, two parameters had the greatest influence on the results of the model: the price reduction of generics versus original branded drugs and penetration rate of generics via the retail chain distribution.Reimbursement rate applied only for the retail chain for all countries.Applying the reimbursement rate only to the retail chain had a small impact on the pharmaceutical budget of each country .Cumulative distributions of simulated budget impacts are presented in The probabilistic sensitivity analysis allowed defining the probability of occurrence of a predetermined impact. This was illustrated in In Germany, the probabilistic sensitivity analysis showed a very low net budget impact compared to the base case. Half of the simulations were between −€3,203 and −€1,116 million with a base case at −€831 million. This was explained by the fact that the time to market for a new drug after marketing approval was fixed to zero in the base case, so the only possible evolution of this parameter in the sensitivity analyses was an increased time. This provided an asymmetric variation in one single direction, as time to market could not be negative. Moreover, time to market for the new drug was found to be a key driver of the results.This study provided a new, highly flexible model that allows testing robustness and a new methodology that freed forecasting from the historical data, which were the main basis in most approaches.The new methodology was used in this study to forecast pharmaceutical expenditure in seven EU MS over a 5-year forecasted period. Results of this forecasted project showed a consistent, but variable in magnitude, reduction in pharmaceutical expenditure in all countries with the exception of Poland. Two parameters had a great influence on expenditure in the selected countries, apart from Portugal and Poland: price reduction of generics versus original branded drugs and penetration rate of generics via retail distribution chain. These parameters were identified using a deterministic one-way sensitivity analysis, which permitted the identification of the main parameters impacting the pharmaceutical expenditure forecast of each country. This methodology measured the uncertainty surrounding the model's results and showed that the projected net budget impact was not altered with variations in parameters. Different pricing and reimbursement policy decisions on health expenditures were also tested with this methodology, providing probabilistic analysis to support policy decision making.This modelling exercise was based on several assumptions discussed below.For the generic model, hospitals were assumed to exclusively use generic or biosimilar products, when available. However, this is not always the case in the real world, as hospitals can use branded drugs, although only if their price is lower than or equal to the generic or biosimilar product's price. Thus, with this premise, this hypothesis had no consequence on the reliability of the model outputs.The risk of drug development failure was estimated by therapeutic area, due to differences related to new drugs’ features which depend on the therapeutic area. This relevant methodology fits the budget impact analysis that was also oriented per therapeutic area.The budget impacts of drugs approved in 2010 and 2011 were estimated by the board of experts according to the sales already generated and to the new medicine's ASMR assessment by the HAS complemented by the SMC review. Recommendations were assumed to be comparable in the seven countries even if it was not certain that this was the case. The HAS and SMC are the only health authorities that provided a comprehensive and argued review of all products reaching the market at the time surrounding launch. Both agencies use different methodologies: the SMC relies mainly on cost-effectiveness ratios, and the HAS relies mainly on clinical efficacy and effectiveness. Therefore, this method was considered to provide a reasonable view of the product's potential market value used for the forecasting exercise.The reliability of the methodology used for assessing the budget impact of new oncology drugs in Greece, Hungary, Poland, and Portugal was confirmed using Germany instead of France as reference country, with stable results. Except for Poland, which seems to be enjoying a substantial increase in its gross domestic product, most countries are experiencing a tight overall budget and might have difficulties finding new revenue to fund additional expensive treatment options. Therefore, this method was considered to provide a reasonable estimate of oncology drugs’ impact in those countries.New drugs to be approved, such as combinations of already approved products, me-too drugs, and new formulations of already approved products with no additional major clinical value, were considered to have no budget impact. However, having no budget impact does not mean not having any sales. In fact, nowadays, with increased pressure on EU MS budgets, only marginally innovative and non-innovative products are not expected to impact drug expenditure budgets. Such products will likely generate substantial sales but only by shifting budgets from older to new products. HTA regulations at the national level and health insurances have shown a substantial strengthening trend that is making it increasingly difficult for such products to impact the drug budget.For the new drug model, peak sales were considered to be reached over a period of 3 years. This period is short compared to the average used in forecasting, where peak sales were usually achieved over 5 years. However, a faster uptake seemed appropriate as only innovative products were considered to affect the drug budget.A ratio of ex-factory to retail sales was used as a rough aggregated estimate that was not representative of the detailed retail operating cost. In most countries, the cost of distribution chain is a complex calculation that depends on multiple parameters and should not be considered as a simple proportion. However, from an overall budget impact, it was an acceptable option to use such an overall ratio.Non-orphan drugs with no phase II study results were considered unlikely to reach the market and generate significant sales before December 2016. However, even with negative phase II results, some pharmaceutical companies launch a phase III study in parallel with a new phase II study. Thus, some drugs not selected in the study might get access to the market during the study period. These cases were presumed to be quite rare, as risk of failure without a positive phase II remains high, and very few products are developed in parallel phases II and III.Market development of products that were launched before 2010 and not expected to become generic in the considered period was not taken into account. Such products were likely to have some impact by increasing or decreasing their market share according to various possible events. This impact was expected to have low relevance to the study results due to the fact that it could lead at the same time to a quite similar increase and decrease of the pharmaceutical budget.One global rate per country was applied for reimbursement on the total of pharmaceutical expenditures, including hospital expenditures, based on the mean of co-payment levels in place in each country. It was assumed, and confirmed in a specific scenario accounting for the reimbursement rate only in the outpatient sector, that this would not substantially affect the model's results.Growth domestic product per capita was not considered to increase, even though it might have opened access to innovative molecules at a faster pace than it does today.One limitation of this study is the amount of data needed to be collected and the amount of work incurred in order to analyze each drug individually. It has been especially complicated to obtain data on drugs’ patent expiry dates for all countries, due to the extensive range of patents available for one product . The large number of patent litigations surrounding the launch of generics and biosimilars is a consequence of the difficulty to appreciate the actual date of intellectual property (IP) loss, and the value of some additional patents used to reinforce IP protection. Several model inputs were based on board of experts’ insight (based on literature review data). The board looked at each new drug individually to assess its clinical potential and translate it into commercial potential. Such methods are simple, clear, and quite reliable when changes are occurring progressively. It allows for a case-by-case specific assessment but relies only on the experts’ capability and judgement. In this study, the board was supported by local experts providing reassurance on such limitations.Today, historical benchmarks are less reliable because of the disruption of the value appreciation of new drugs in most countries. This evidence-based methodology appears robust for pharmaceutical expenditure forecasting. It allows one to assess the uncertainty surrounding estimations, and it is independent from historical sales and market development, and thus particularly adapted to payers’ decisions making in a fast-changing environment. The reliability of this methodology could be confirmed by comparing the real pharmaceutical expenditure to the forecasted expenditure.


Francophones may experience poorer health due to social status, cultural differences in lifestyle and attitudes, and language barriers to health care. Our study sought to compare mental health indicators between Francophones and non-Francophones living in the province of Manitoba.Two populations were used: one from administrative datasets housed at the Manitoba Centre for Health Policy and the other from representative survey samples. The administrative datasets contained data from physician billings, hospitalizations, prescription drug use, education, and social services use, and surveys included indicators on language variables and on self-rated health.Outside urban areas, Francophones had lower rates of diagnosed substance use disorder  and of suicide and suicide attempts , compared with non-Francophones, but no differences were found between the groups across the province in rates of diagnosed mood disorders, anxiety disorders, dementia, or any mental disorders after adjusting for age, sex, and geographic area. When surveyed, Francophones were less likely than non-Francophones to report that their mental health was excellent, very good, or good .The discrepancy in how Francophones view their mental health and their rates of diagnosed mental disorders may be related to health seeking behaviours in the Francophone population. Community and government agencies should try to improve the mental health of this population through mental health promotion and by addressing language and cultural barriers to health services. Mental health has profound effects on the overall well-being and functioning of people, their families, and their communities. Mental health problems negatively impact quality of life,7Our study sought to compare the rates of mental health indicators of Francophones and non-Francophones in 2 study populations. Based on previous studies, we hypothesize that the mental health of Francophones in Manitoba will not be different if their SES is comparable with that of non-Francophones. Extensive data linkage using administrative and survey databases was required to create the matched cohort by selecting Francophones and non-Francophones while maintaining their anonymity. Having better knowledge of the mental health status of a population is helpful for policy development and service planning and contributes to the vitality of that population.We examined 2 study populations: one from the Population Health Research Data Repository (referred to henceforth as the Repository) housed at the MCHP at the University of Manitoba, and the other from representative surveys, namely, the CCHS, the NPHS, and the Manitoba HHS. Both study populations are from the province of Manitoba, located in the centre of Canada. Manitoba has a population of 1.2 million, with more than one-half of the population living in the provincial capital city of Winnipeg. The other half of the population lives in rural and northern regions or in small cities with populations of 60 000 or less.Francophones living in areas where they are a minority may not be comfortable seeking help for mental health concerns.Offering French-language health services may improve access to mental health services for Francophones.Mental disorder indicators were from administrative data and miss people who are not seeking help for mental health concerns.A selection bias may be present as not all Francophones were identified with the use of administrative databases.A total of 40 600 Francophones and 121 800 non-Francophones were included in the Francophone and matched cohort using the Repository databases at the MCHP. These databases were scanned for language flags, such as maternal languages, linguistic preferences, or self-identification as a Francophone. The Repository houses a collection of administrative databases that were originally collected to administer health, education, and social services in Manitoba. These data capture virtually all contacts by Manitoba residents when they access provincial services. The Repository holds no personal identifying information, such as names and addresses; and a numeric identifier is scrambled before the data are deposited in the Repository. These datasets are linkable at an individual level across files and over time because the identifier is scrambled in the same way for each file. The data in the Repository have been examined extensively and validated for research purposes.Several steps were required to create the Francophone cohort, including the selection of Francophones using MCHP administrative data and survey data, as well as the addition of first-degree family members through health registry linkage. An initial cohort of 19 396 Francophones was created from the administrative and survey databases using language flags. These language indicators varied across databases in both how they were recorded and how well they were captured. They included attending a school offering a Français program, residence in Francophone personal care homes, attending a Francophone child care centre, requesting health-related correspondence in French in the home care or the immunization programs, as well as having French as their maternal language on a kindergarten developmental measure, and reporting being Francophone on representative surveys, namely, the CCHS, the NPHS, and the HHS. Many years of data were available, which increased our ability to identify Francophones for purposes of our study .The Francophone cohort was supplemented by adding first order family members of the initial cohort. This is possible because children of Manitoba residents have the same health identification number as their parents until they are 18 years old. We estimated that about two-thirds of the additional family members would be French speaking and that the other third would be closely linked to the Francophone community through family ties. The Francophone cohort contained 46 954 people after the family linking was completed and 40 600 remained in the province and alive for the study period from 1998 to 2008. The 2006 Canadian Census estimates that there were 50 000 Francophones in Manitoba.n = 1627), the NPHS , and the Manitoba HHS . The linkage is done through a health numeric identifier, anonymously scrambled by the health department, common to the Repository data and the data collected through the surveys. A total of 2342 Francophones and 39 906 non-Francophones were available using respondents from these representative surveys. Variables (both directly reported and derived) available in these surveys included the respondent’s mother tongue, language used at home, and the first official language learned. Data from 7 CCHS cycles were pooled based on methodology recommended by Statistics Canada.15Permission was granted to link the Repository data to Francophones found in the CCHS  was matched with 3 non-Francophone people (n = 121 800). The non-Francophones for the matching procedure were randomly pulled from a pool of all Manitobans with the same age, sex, and health districts where they lived on December 31, 1998. The health districts, determined by postal codes and used as a proxy for socioeconomic and environmental influences, have populations on average of 55 000 people. In rural areas or areas with higher concentrations of Francophones, it was necessary to search for matches in neighbouring districts. To minimize the introduction of systemic biases from the matching procedure, we used person-years to account for the varying lengths of time that the data were available for each person, such as new births and people newly eligible for health coverage. We corrected for the issue of immortal time by requiring that the non-Francophone matches be alive on the day their matched Francophone cohort member was surveyed or otherwise identified in the sample. Second, results obtained in the Repository study population were compared with results from the representative survey study population for all the mental health indicators except suicide attempts and suicide deaths.Two methods were used to address possible selection biases in the Francophone and matched cohort derived from the Repository, which included matching and comparing results with a representative survey sample. Each person in the Francophone cohort , pharmaceutical prescriptions dispensed, CCHS, NPHS, HHS, and census files . The definitions of these mental health variables are found in All data analyses were conducted using SAS version 9.3 . RRs, in addition to crude and adjusted rates, were calculated to reflect the relative difference between both study populations. The count of events for each indicator was modelled using generalized linear modelling, suitable for nonnormally distributed data such as counts. Suicide and suicide attempts were modelled using a Poisson distribution, which is indicated for very rare events, and the other mental disorder indicators were modelled using a negative binomial distribution, which is indicated for relatively rare but highly variable counts. Age and sex were included in the models to adjust for differences in regional age and sex distributions. Self-rated mental health was directly standardized to the combined weighted CCHS survey Manitoba population aged 12 years and older. Statistical testing, using bootstrapping, was conducted to determine differences in the RRs between the Repository and survey study populations.n = 898; SUD, n = 1182). These in-depth analyses were conducted on these indicators to further examine unexpected differences found. Two models were examined, a basic model with adjustments for age, sex, and geographic region that closely replicated the results of our main analyses and a full model that also included sociodemographic and lifestyles variables.Logistic regression was used to explore the impact of being Francophone on positive self-rated mental health and SUD while controlling the effects of other explanatory variables from the survey data  and the matched cohort of other Manitobans (n = 121 800) in the Repository study population were similar because of the matching procedure. Francophones and non-Francophones had the same percentage of males (48%) and the same age distribution . Overall, Francophones in rural areas are living in slightly more socioeconomically advantaged areas, and in urban areas are living in slightly less socioeconomically advantaged areas, compared with other Manitobans. The characteristics shown in n = 1182) and non-Francophones (n = 18 832) in the survey study Repository.Age, sex, and area-level income of the Francophones . The first part of In To our knowledge, the mental health of Francophones in Manitoba has not been examined using administrative databases or representative survey data. We had expected to find no differences in the mental health indicators between the linguistic groups because we had carefully selected a matched cohort for comparison by age, sex, and geographic region as a proxy for SES. The finding that no differences were found in the rates of mood disorders, anxiety, and dementia are consistent with more recent studies., p 123Some of the social and cultural protective factors surrounding suicidality may account for the lower rates of diagnosed SUD among Francophones living outside of Winnipeg. Further analyses with the survey data confirmed that being Francophone was associated with lower SUD rates after controlling for a range of sociodemographic and lifestyle factors. Alcohol use in social settings is well accepted in French culture as it is among Francophones in Manitoba, which could potentially be both a risk factor and a protective factor. European research found that binge drinking is more prevalent in Northern, Western, and Eastern countries than those in the southern parts of Europe, suggesting that “binge drinking was less likely in countries in which alcohol is integrated into everyday life compared to countries where heavy drinking on week-ends was more culturally accepted.”18The apparent contradiction found in our study between the self-rated mental health survey item and the mental illness diagnoses recorded in the administrative data may be because we are measuring 2 different aspects of mental health. Responses to this self-rated question were closely associated with responses from the Mental Health Continuum, an extensive measure of emotional, psychological, and social well-being.In our study, the mental health indicators, with the exception of the self-rated mental health indicator, were calculated for residents who were diagnosed by a physician, and therefore were among those who actually sought help. Francophones living in an environment where French is a minority language have limited access to French-language health services, and accordingly may not be seeking help for mental health concerns. This may partly explain the discrepancy between the poorer self-rated mental health and lower or similar rates of diagnosed mental disorders. Research has shown that the positive impact of language in health care delivery is through clear communication with the health care practitioners and through its role in the therapeutic relationship. People are more likely to express their concerns, ask questions, and follow health recommendations if they are well connected to their health care providers.Studying the health of Francophones in Canada has been challenging because of the lack of population-based databases with the language variables required to identify them.The matching technique used also strengthens our confidence in the results found in our study. Ensuring that each Francophone selected was matched with 3 other Manitobans on age, sex, and geographic region provided a method for controlling for these important factors. We were able to ensure that the area-level indicator of SES was comparable across groups. We felt that this was a reasonable comparison as Francophones in Manitoba are not socioeconomically disadvantaged, but rather are similar to other Manitobans regarding income, education, and employment levels.Rates of diagnosed mental disorders of Francophones and non-Francophones were based on actual medical claims, hospitalizations, and prescriptions. The strength of these indicators is that they provide objective rates of people treated for mental disorders and are not biased by self-assessment or recall. While they have been carefully created through consultation with health professionals, an important limitation is that they have not been validated by comparing to a gold standard, such as a standardized interview by a mental health specialist. Another limitation is that we cannot ascertain whether the differences are because help seeking behaviours may differ between linguistic populations. A recent report documented differences in diagnosed rates of mood disorders and SUD across regions in Manitoba using these indicators.Our study shows that Francophones in Manitoba have similar rates of diagnosed mental disorders as other Manitobans, with the exception of Francophones outside the large urban area of Winnipeg who have lower rates of diagnosed SUD and lower rates of suicide attempts and deaths. However, Francophones were less likely to rate their mental health as positive, compared with other Manitobans. This discrepancy in how Francophones view their mental health and their rates of diagnosed mental health problems may be related to health seeking behaviours in the Francophone population. Community and government agencies should try to improve the mental health of this population through mental health promotion and by addressing language and cultural barriers to health services. Further research can consider if there are differences in health care seeking behaviour that may be affecting the findings presented here. Also of interest would be studying whether policies developed within Manitoba regarding linguistic rights contribute to the mental health status of Francophones.