Un justiciable mécontent lève un rideau, sans doute usé. Une robe noire apparaît alors et énonce: « Donne moi le fait, je te donnerai le droit ! ». Ce juge s’écarte ensuite afin d’écouter les échanges des parties. Il reprend la parole, reformule le cas échéant certaines répliques et démêle l’intrigue en retenant, voire aménageant, une des fins proposées par les parties. Voici la trame, désormais classique, de l’instance dressée par les principes directeurs du procès civil. Les plaideurs auraient ainsi pour rôle de délimiter la matière litigieuse et, partant, la saisine du juge. Ce dernier devrait, dans les limites ainsi tracées, lui appliquer le droit afin de satisfaire à sa fonction juridictionnelle. La question des rôles respectifs du juge et des parties sur les éléments de l’instance ne saurait toutefois être appréhendée dans sa complexité et son dynamisme par ces seules règles. La distinction du fait et du droit, parce qu’elle ne correspond qu’imparfaitement aux éléments de l’instance réellement opérant, la prétention et le moyen, offre une assise peu opportune à la détermination des activités judiciaires et leur exercice. Par ailleurs, lorsqu’ils sont confrontés à la réforme permanente de la matière, la stabilité de ces principes interpelle, et étonne même.En considérant les éléments de l’instance et leur traitement au-delà des dispositions préliminaires du code, et au-delà du code lui-même, il pourra être énoncé que ces principes directeurs tendent à devenir davantage aveuglants qu’éclairants. En effet à la lecture de l’article 12 du Code de procédure civile, fondement des pouvoirs et devoirs du juge sur le droit, il est par exemple établi que le juge tranche le litige conformément aux règles de droit qui lui sont applicables. On ignore ainsi que, depuis 2008, le juge n’a pas l’obligation de rectifier le fondement juridique erroné de la demande, comme on ne se doute pas plus que son obligation de statuer se limitera, depuis 2017, aux seules prétentions contenues dans le dispositif des dernières conclusions, certes rédigées par avocat. On n’anticipe encore moins que, en dépit de tous ces phénomènes de réduction de ce qui devra être tranché, l’autorité de chose jugée va, quant à elle, au contraire, s’étendre pour couvrir le litige entendu comme tout ce qui aurait dû être tranché. Les parties recueillent ainsi la charge du droit initialement dévolue au juge. La procédure civile offre dès lors un nouveau visage au principe dispositif : la responsabilisation des parties et la déresponsabilisation de la justice dans la réalisation des droits.L’accélération du traitement des affaires rapproche l’instance civile du théâtre par l’exigence de l’unité de temps. Elle s’en éloigne en revanche s’agissant de la règle de l’unité de lieu, les politiques judiciaires affichant clairement leur volonté de promouvoir le règlement amiable des litiges. Il n’y a plus qu’à espérer que la distribution soit à la hauteur du programme. / A displeased person answerable to the law raises a curtain, most likely worn out. A black robe appears and announces: ‘Give me the facts, I will give you the law!” This judge then steps aside in order to listen to the exchanges between various parties. He speaks again, change when required some turn of sentences, untangle the plot by retaining, even rearranging one of the ending proposed by the parties. Here is the context, now classic, of the instance established by the guidelines of civil trial. The role of the litigant is thus to delimit the litigious matter and hence, the referral to the judge. The latter should, within the limits, apply to him the law in order to satisfy his jurisdictional function. The question of the respective roles of the judge and the parties over the elements of the case cannot, however, be apprehended in its complexity and dynamism by these rules alone. The distinction between fact and law, because it corresponds only imperfectly to the elements of the actual operative instance, the claim and the plea, provides an unfavourable basis for the determination of judicial activities and their exercise. On the other hand, when confronted with the permanent reform of matter, the stability of these principles challenges, and even astonishes.By considering the elements of the case and their treatment beyond the preliminary provision of the Code, and beyond the Code itself it may be stated that these guiding principles tend to become more blinding than enlightening. Indeed, in reading Article 12 of the Code of Civil Procedure, the basis of the powers and duties of the judge on the law, it is for example established that the judge settle the dispute in accordance with the rules of law that apply to it. It is thus not known that since 2008 the judge has no obligation to rectify the erroneous legal basis of the claim, the same way we do not conceive that his obligation to rule will, since 2017, be limited to the claims contained in the device of the conclusions, admittedly written by lawyers. It is even less anticipated that, in spite of all these phenomena of reduction of what will have to be settled, res judicata will, on the contrary, extend to cover the dispute understood as all that should have been decided. The parties thus collect the burden of the right initially devolved on the judge. Civil procedure therefore offers a new face to the operative principle: the responsibility of the parties and the disempowerment of justice in the realization of rights.The acceleration of the treatment of the cases brings the civil authority closer to the theatre by the requirement of the unit of time. On the other hand, it departs from the rule of unity of place, as judicial policies clearly reflect their desire to promote the amicable settlement of disputes. There is more to hope that the distribution is up to the programme

This thesis assesses the current status of Canadian prescription drug regulation and the policy drivers that guide this process. This analysis is accomplished by first providing a general survey of the steps, law, and institutional players involved in the full life-cycle of a drug. Next the evolution of current clinical trials and the gaps that the present legal regime creates in the scientific standards employed in clinical research is reviewed. This is followed by a discussion of how commercialization (innovation) and speed of approval (market access) are slowly becoming the dominant policy drivers for the Canadian regime. Finally a discussion of the proposed Progressive Licensing model, and Bill C-51-An Act to Amend the Food and Drug Act, raises the concerns with a shift to a system largely based on risk assessment and post-market monitoring (pharmacovigilence).

Orientador: Rosângela Gonçalves Peccinini / Resumo: A doença de Chagas é uma enfermidade que afeta milhões de pessoas no mundo, principalmente em países em desenvolvimento. No Brasil, o único fármaco disponível para tratamento desta doença é o benzonidazol (BNZ). Atualmente o regime posológico para adultos consiste na administração deste fármaco na forma de comprimidos de liberação imediata de 100 mg em duas ou três tomadas diárias, durante 60 dias. Apesar da elevada eficácia desse fármaco na fase aguda da doença (aproximadamente 70%), os eventos adversos são frequentes e muitas vezes causam a interrupção do tratamento. Diante desse cenário, o Laboratório de Tecnologia de Medicamentos (LTM) da Universidade Federal de Pernambuco (UFPE) desenvolveu comprimidos de liberação prolongada, visando a redução da frequência de administrações do fármaco e a melhoria do tratamento com doses mais precisas. Em estudos pré-clínicos foram observadas vantagens da administração do comprimido de liberação prolongada na cinética do fármaco benzonidazol quando comparada a administração do comprimido de liberação imediata (formulação convencional). Entretanto, a continuidade do desenvolvimento do produto farmacêutico para aplicação terapêutica exige a avaliação em humanos. Logo, o objetivo deste trabalho foi reunir todas as informações e documentos necessários para a elaboração do protocolo de estudo clínico da nova formulação de liberação prolongada para futura submissão ao CEP e à ANVISA. Estabeleceu-se o protocolo para estudo Clínico de fase I –... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Chagas disease affects millions of people worldwide, especially in developing countries. In Brazil, the only drug available for treatment of this disease is benzonidazole (BNZ). Currently, the dosage regimen for adults consists of administration of this drug in the form of 100 mg immediaterelease tablets in twice or three times a day for 60 days. Despite the high efficacy of this drug in the acute phase of the disease (approximately 70%), adverse effects are common and often cause discontinuation of treatment. In this scenario, the Laboratory of Drug Technology (LTM) of the Federal University of Pernambuco (UFPE) has developed extended-release tablets aimed at reducing the frequency of drug administration and improving treatment at more precise doses. In preclinical studies, advantages of extended-release tablet administration have been observed in the kinetics of the drug benzonidazole when compared to the administration of the immediate release tablet (conventional formulation). However, the continued development of the pharmaceutical product for therapeutic application requires evaluation in humans. Therefore, the objective of this study was to gather all the information and documents necessary for the elaboration of the clinical study protocol of the new extended release formulation for future submission to the IRB (Institutional Review Board) and Brazillian Health Regulatory Agency (ANVISA). The protocol for Phase I clinical study - comparative, open, randomized, cross-o... (Complete abstract click electronic access below) / Mestre

Submitted by Carolina Peres null (carol_peres88@hotmail.com) on 2017-10-20T13:48:07Z No. of bitstreams: 1 Dissertação completa mestrado.pdf: 3043086 bytes, checksum: 409a3054d7b6e44ea30ba5eca7aac1bf (MD5) / Approved for entry into archive by Luiz Galeffi (luizgaleffi@gmail.com) on 2017-10-23T19:13:46Z (GMT) No. of bitstreams: 1 peres_c_me_bot.pdf: 3043086 bytes, checksum: 409a3054d7b6e44ea30ba5eca7aac1bf (MD5) / Made available in DSpace on 2017-10-23T19:13:46Z (GMT). No. of bitstreams: 1 peres_c_me_bot.pdf: 3043086 bytes, checksum: 409a3054d7b6e44ea30ba5eca7aac1bf (MD5) Previous issue date: 2017-08-31 / A doença de Chagas é uma enfermidade que afeta milhões de pessoas no mundo, principalmente em países em desenvolvimento. No Brasil, o único fármaco disponível para tratamento desta doença é o benzonidazol (BNZ). Atualmente o regime posológico para adultos consiste na administração deste fármaco na forma de comprimidos de liberação imediata de 100 mg em duas ou três tomadas diárias, durante 60 dias. Apesar da elevada eficácia desse fármaco na fase aguda da doença (aproximadamente 70%), os eventos adversos são frequentes e muitas vezes causam a interrupção do tratamento. Diante desse cenário, o Laboratório de Tecnologia de Medicamentos (LTM) da Universidade Federal de Pernambuco (UFPE) desenvolveu comprimidos de liberação prolongada, visando a redução da frequência de administrações do fármaco e a melhoria do tratamento com doses mais precisas. Em estudos pré-clínicos foram observadas vantagens da administração do comprimido de liberação prolongada na cinética do fármaco benzonidazol quando comparada a administração do comprimido de liberação imediata (formulação convencional). Entretanto, a continuidade do desenvolvimento do produto farmacêutico para aplicação terapêutica exige a avaliação em humanos. Logo, o objetivo deste trabalho foi reunir todas as informações e documentos necessários para a elaboração do protocolo de estudo clínico da nova formulação de liberação prolongada para futura submissão ao CEP e à ANVISA. Estabeleceu-se o protocolo para estudo Clínico de fase I – biodisponibilidade comparativa, aberto, aleatorizado, cruzado e monocêntrico. A administração foi estabelecida em dois tratamentos, duas sequências, dois períodos, nos quais os participantes recebem, em cada período, a formulação teste ou a formulação referência. Serão realizados dois estudos independentes, no qual o primeiro estudo, os participantes estarão em jejum (Estudo I) e no segundo estudo, estarão alimentados (Estudo II). Serão 24 participantes para cada estudo, sendo 12 participantes de cada sexo. Os resultados deste estudo proporcionarão informações para avaliar se a administração da formulação Teste, benzonidazol 200mg, determina níveis plasmáticos semelhantes aos da formulação Referência, benzonidazol 100mg e se os mantém por período suficiente para a assunção de uma administração diária. Esta avaliação culminará com a decisão sobre a substituição da apresentação atualmente utilizada no tratamento da tripanossomíase pela nova formulação de liberação prolongada. / Chagas disease affects millions of people worldwide, especially in developing countries. In Brazil, the only drug available for treatment of this disease is benzonidazole (BNZ). Currently, the dosage regimen for adults consists of administration of this drug in the form of 100 mg immediaterelease tablets in twice or three times a day for 60 days. Despite the high efficacy of this drug in the acute phase of the disease (approximately 70%), adverse effects are common and often cause discontinuation of treatment. In this scenario, the Laboratory of Drug Technology (LTM) of the Federal University of Pernambuco (UFPE) has developed extended-release tablets aimed at reducing the frequency of drug administration and improving treatment at more precise doses. In preclinical studies, advantages of extended-release tablet administration have been observed in the kinetics of the drug benzonidazole when compared to the administration of the immediate release tablet (conventional formulation). However, the continued development of the pharmaceutical product for therapeutic application requires evaluation in humans. Therefore, the objective of this study was to gather all the information and documents necessary for the elaboration of the clinical study protocol of the new extended release formulation for future submission to the IRB (Institutional Review Board) and Brazillian Health Regulatory Agency (ANVISA). The protocol for Phase I clinical study - comparative, open, randomized, cross-over and monocentric was established. The administration was established in two treatments, two sequences, two periods, in which the participants receive, in each period, the test formulation or the reference formulation. Two independent studies will be performed, in which the first study, participants will be fasted (study I) and in the second study, they will be fed (study II). There will be 24 participants for each study, 12 participants of each sex. The results of this study will provide information to assess whether administration of the Test formulation, benzonidazole 200mg, determines plasma levels similar to those of the Reference formulation, benzonidazole 100mg, and if these levels are maintained for a sufficient time for daily administration. This evaluation will culminate with the decision on the replacement of the present presentation used in the treatment of trypanosomiasis by the new extendedrelease formulation.

The present study asked two important questions: Does prejudicial pretrial publicity produce bias which may impair juror objectivity and, if it does, can voir dire remedy its untoward effects? Subjects were 68 college undergraduates whose political attitudes had been assessed and who had or had not read case-specific pretrial publicity one week before viewing a murder trial. Trial proceedings took place at the University of Miami law school. Voir dire, trial viewing, and deliberations were conducted in UM's moot courtroom. As predicted, analyses revealed main effects for both voir dire and pretrial publicity such that pretrial publicity increased conviction rate and the extended voir dire decreased conviction rate, but the extended voir dire failed to reduce the specific prejudicial effect of pretrial publicity. These findings suggest that prejudgment of a general nature (e.g., confusion about legal concepts) may be neutralized by an extended voir dire but that prejudice specifically created by exposure to inflammatory news stories is not offset by an extended voir dire format. There is reason to believe, however, that with more time spent explaining case facts and with greater attention to individual jurors, voir dire could eliminate even the specific prejudice created by pretrial publicity.

My diploma thesis deals with the Clinical trial in the Czech Republic in the period from 1989 to present and on its impact on management in organizations dealing with clinical trials. The aim of this thesis is to identify key changes that occurred in the clinical trial and to identify how these changes infuenced the management of clinital trial organizations. This will be done based on the qualitative research. The theoretical part provides information about the history of the clinical trial, about internation and the Czech legislation, including ethical principles, the submission process including description of institution that are reviewing the clinical research. The theory also explains the issue of management, its organizational developments and its expected development in the future. In the research part I described the chosen research method, which extend from the semi- structured interview after the pilot part to the use of the focus group method - in the combination with semi-structured interview. Based on these interviews and focus group have been evaluated 7 parts to describe the evolution of the clinical trial and its impact on the management of clinical trials, including one topic that addresses the expected development of this field in the future. Key words: clinical trial, clinical...

Puisque l'institution judiciaire dans les sociétés démocratiques est le garant des droits et libertés des individus, cette institution doit disposer tous les atouts qui lui garantissent de jouer ce rôle. La Mauritanie a connu à l'époque moderne l’instauration de ce pouvoir judiciaire, durant deux étapes importante, la première sous le contrôle du colonialisme français, qui a soumis le pays depuis plusieurs décennies, et la dernière après l’indépendance où la codification de la première organisation judiciaire en Mauritanie en date du 27 juin, 1961 avec la loi N° 61-012. En Mauritanie la justice dans son ensemble souffre de certain de maux, et l’accès à la justice pour l’ensemble des citoyens est entravé par beaucoup d’obstacles, et menacé par un certain nombre des insuffisances, et de nos jours, le droit à un procès équitable est un droit primordial, garanti par un ensemble de principes issus des conventions internationales dans le domaine de protection de droit de l’Homme. Le droit à un procès équitable est donc parmi des droits fondamentaux de l'être humain .il y a un certain nombre de conditions qui doivent être remplies pour assurer un procès équitable afin de protéger les droits des personnes. Afin de mettre en évidence et de clarifier les obstacles observés sur ces aspects, cette étude passe en revue l’organisation de la justice au pays, ainsi qu’une analyse des lieux des faille, tant sur le plan des empêchements issus des raisons socioéconomiques et organisationnelle, que celui de la non-conformité aux exigences internationales en la matière. Cette étude a présenté un ensemble de propositions, soient la révision de nos textes afin d’introduire davantage une manière plus efficace de ces principes, en particulier le principe de la collégialité, la publicité, et les droit des défenses. En renforçant les compétences du juge unique au niveau des tribunaux de première instance. Sans oublier d'assurer une plus grande spécialisation des magistrats tant au niveau des tribunaux des premières instances qu’au niveau de la cours d'appel. Toutes ces propositions ont pour but d’essayer d‘améliorer la situation actuelle, pour faire en sorte qu’il ait au moins l’existence de conditions minimales pour un procès équitable, car la violation du droit à un procès équitable, reste toujours une cause de préoccupation pour toute l’humanité. / As the judicial institution in democratic societies is the guarantor of the rights and freedoms of individuals, such institution must have all the means that allow it to play this role. Mauritania has known in its modern history the establishment of the judicial power, through two important steps. First was in the French colonialism, which has ruled the country for several decades, and the last was after independence with the codification of the first judicial organization in Mauritania on June 27, 1961 by Law No. 61-012. In Mauritania, justice had as a whole suffered from several problems and access to justice for all citizens is hindered by many obstacles, and threatened by a number of shortcomings. Today, the right to a fair trial is a primary right, guaranteed by a set of principles derived from international conventions as a part of human rights. The right to a fair trial is recognized as the fundamental among the human being rights but there are some conditions that must be met to ensure a fair trial in order to protect the rights of individuals. In order to highlight and clarify the obstacles observed in these aspects, this study reviews the organization of justice in the country, as well as it tries to provide an analysis of the places of the deficiencies as well as the impediments causing by socioeconomic reasons and organization and also the non-compliance with the international requirement in this area. This study gives some proposals, through the revision of the texts by introducing more strongly some principles. in particular the principle of collegiality, and the right of defense and by strengthening the prerogatives of the unique judge in the first instance courts and also in providing more specialization of the magistrates as well at the courts of the first instances as at the level of the appeal court. All these proposals aim to improve the current situation, for setting up the minimal conditions for a fair trial, because the violation of the right to a fair trial remains great concern for all humanity.

published_or_final_version / Sociology / Master / Master of Social Sciences

Background: There is a great need for effective treatments for mental health problems. Randomised controlled trials are the gold standard for evaluating treatments, however recruitment into trials is challenging, highlighting a clear need for evidence-based recruitment strategies. This thesis aimed to systematically develop a recruitment intervention and evaluate its effectiveness for improving the recruitment of participants into mental health trials. Methods: A mixed-methods approach, adopting the Medical Research Council’s complex interventions framework: 1) a systematic review to identify the evidence base and describe the factors affecting recruitment into depression trials; 2) a qualitative study to understand patients’ decision-making process in declining to enrol in a depression trial; 3) development of a recruitment intervention, using Participatory Design methods; and 4) evaluation of the recruitment intervention, using a randomised controlled trial, embedded in an ongoing mental health trial (the EQUIP trial). The primary outcome was the proportion of participants enrolled in EQUIP. Results: From the systematic review, a conceptual framework of factors influencing the decision to participate was developed, which highlighted that the decision to enrol involves a judgement between risk and reward. Findings suggested that patient and public involvement in research (PPIR) might be advertised to potential participants to reduce such perceived risk. The qualitative study found positive views of trials. Interviewees’ decision making resembled a four-stage process; in each stage they either decided to decline or progressed to the next stage. In Stage 1, those with an established position of declining trials opted out – they are termed ‘prior decliners’. In Stage 2, those who opted out after judging themselves ineligible are termed ‘self-excluders’. In Stage 3, those who decided they did not need the trial therapy and opted out are termed ‘treatment decliners’. In Stage 4, those who opted out after judging that disadvantages outweighed advantages are termed ‘trial decliners’. While ‘prior decliners’ are unlikely to respond to trial recruitment initiatives, the factors leading others to decline are amenable to amelioration as they do not arise from a rejection of trials. We recruited a host mental health trial (EQUIP), and worked with key stakeholders, including mental health service users and carers, to develop an intervention using a leaflet to advertise the nature and function of the PPIR in EQUIP to potential trial participants. 34 community mental health teams were randomised and 8182 patients invited. For the primary outcome, 4% of patients in the PPIR group were enrolled versus 5.3% of the control group. The intervention was not effective for improving recruitment rates (adjusted OR= 0.75, 95% CI= 0.53 to 1.07, p=0.113). Conclusions: This thesis reports the largest ever trial to evaluate the impact of a recruitment intervention. It also reports the largest trial of a PPIR intervention and makes a contribution to the evidence base on trial recruitment as well as to that assessing the impact of PPIR. Two further embedded trials are underway to evaluate the effectiveness of different versions of the recruitment intervention in different trial contexts and patient populations. This will also allow the results to be pooled to generate a more precise estimate of effect; to evaluate the impact of the intervention on trial retention; and to explore patient experiences of receiving the intervention.

Background The World Health Organization (WHO) defines health as a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity. Despite its importance, mental health provisions are often limited. In 2015, Indonesia had only 773 psychiatrists for 250 million residents. This shortage of specialist mental health professionals is shared by most Low- and Middle-Income Countries (LMICs) and is reflected in the Treatment Gaps in this region indicating the very small proportion of people who receive adequate mental health care for their needs. While the median worldwide Treatment Gap for psychosis is 32.2% (Kohn et al., 2004), in Indonesia it is more than 90%. Experts suggested integrating mental health care into primary care, to help bridge this gap (Mendenhall et al., 2014). The systematic introduction of the World Health Organization Mental Health Gap Action Programme into primary care clinics across Indonesia and the presence of a 15-year-old co-location of Clinical Psychologists in Yogyakarta province's primary care clinics presented an opportunity to assess the clinical and cost-effectiveness of both frameworks. Methods This research ("the trial") set out to develop an approach, and then implement it, to compare the adapted WHO mhGAP framework with the existing specialist framework within primary mental health services in Yogyakarta, Indonesia, through a pragmatic, two-arm cluster randomised controlled non-inferiority trial. This design enabled an examination of patients derived from whole populations in a 'real world' setting. The trial involved two phases: a pilot study in June 2016 with the objectives to refine data collection procedures and to serve as a practice run for clinicians involved in the trial; as well as a substantive trial beginning in December 2016. The 12-item General Health Questionnaire (GHQ-12) was established as a 'fairly accurate' screening tool using a Receiver Operating Curve study. Using the GHQ scoring method of 0-0-1-1, a threshold of 1/2 was identified for use in clinical setting, i.e. the context of the trial. The primary outcome was the health and social functioning of participants as measured by the Health of the Nation Outcome Scale (HoNOS) and secondary outcomes were disability as measured by WHO Disability Assessment Schedule 2.0 (WHODAS 2.0), quality of life as measured by European Quality of Life Scale (EQ‐5D-3L), and cost of intervention evaluated from a health services perspective, which aimed to determine the clinical effectiveness and cost-effectiveness of both frameworks at six months. Results During the recruitment period, 4944 adult primary care patients attended 27 participating primary care centres. Following screening (n=1484) and in-depth psychiatric interviews (n=394), 174 WHO mhGAP arm and 151 Specialist arm participants received a formal diagnosis and were recruited into the trial. The number of required participants per treatment arm, to provide statistical power of 0.80 and statistical bilateral significance value of 0.05 was estimated to be 96. A total of 153 participants of the WHO mhGAP arm and 141 of the Specialist arm were followed-up at six months, representing 90.8% of all participants diagnosed. At follow-up, 82% (n=126) participants of the WHO mhGAP arm indicated they had attended at least one treatment session during the trial, significantly more than in the Specialist Arm (69%; n=97), 2 = 7.364, p=0.007. The WHO mhGAP arm was proven to be statistically not inferior to the Specialist arm in reducing symptoms of social and physical impairment, reducing disability, and improving health-related quality of life at six months. Cost-effectiveness analyses show that the Specialist arm was dominant for a unit of improvement in patient outcomes at six months. While the framework is more expensive for the Health System, participants in the Specialist arm were found to have larger improvements. Conclusion Given that both frameworks yielded positive patient outcomes, there is no immediate need to increase the absolute number of specialist mental health professionals in community psychiatry (i.e. replicate the specialist framework outside Yogyakarta). As most psychologists and psychiatrists in Indonesia reside in large cities, the current systematic roll-out of the adapted WHO mhGAP framework might address the need to strengthen non-stigmatising mental health care within community contexts, reflecting the preferences of primary care patients. In districts or provinces which could afford the additional cost, however, the Specialist framework was shown to be better at improving patient outcomes than the adapted WHO mhGAP framework. Existing resources for specialist care can be arranged in a hub-and-spoke (step-up care) model where higher-level interventions are provided for those with greater needs. The proposed model would free-up resources for advanced clinical training of the specialist workforce in key areas of need while keeping specialist services accessible. Trial Registration This trial has been registered with clinicaltrials.gov since 25 February 2016, NCT02700490. Ehical Standards Full ethics approval from the University of Cambridge, UK was received on 15 December 2015 (PRE.2015.108) and from Universitas Gadjah Mada, Indonesia on 14 April 2016 (1237/SD/PL.03.07/IV/2016). A condition of ethics approval from the University of Cambridge is that the investigator is covered by indemnity insurance and that participants are insured for the period of their participation. This was provided by the University of Cambridge Trial Insurance Office (609/M/C/1510). Ethics approval from all the clusters was not required as each cluster (Puskesmas) is a local GP surgery which does not have its own ethics committee. Instead, approval to conduct research at the province of Yogyakarta including all five districts: Kota Yogyakarta, Sleman, Gunung Kidul, Kulon Progo, Bantul Districts was obtained from the Provincial Government Office (070/REG/V/625/5/2016) following ethics approvals. Written consent to participate was obtained from clinicians taking part as well as all patient-participants.