The paper investigates and compares the relationship between inflation and inflation uncertainty under inflation targeting and, alternatively, a conventional fixed exchange rate system, for a group of emerging countries. To do so we estimate GARCH in mean models and we find that there is a bi-directional relationship between inflation and inflation uncertainty under the two monetary regimes. It is also found that the fixed exchange rate regime has no impact on average inflation and inflation inertia, while inflation targeting has been successful at lowering both average inflation and inflation persistence. Since the introduction of fiat money, inflation has become an important problem. This is because inflation may have negative effects on economic dynamics, nominal wages and the intertemporal decisions of market agents. However, the historical evidence on inflation from the last century reveals that the discretionary money standard which are bound to a fixed exchange rate regime and with an independent central bank were less exposed to high inflation . TherefoNonetheless, there is a general consensus that the social and financial costs attributed to inflation are due mainly to uncertainty about future inflation. The nexus between inflation and inflation uncertainty has gained attention in the literature after the Nobel lecture of  pointingHence, a large number of studies have been carried out to assess the validity of Friedman-Ball (F-B) and Cukierman and Meltzer (C-M) hypotheses; the literature has grown after the development of the Auto Regressive Conditional Heteroskedasticity (ARCH) and Generalised ARCH (GARCH) techniques, by  and 7],,7], respTherefore, this paper investigates the nexus between inflation and inflation uncertainty in emerging market economies under two monetary anchors: a soft pegged exchange rate (FER) to the US dollar and IT. The aim of this paper is twofold. Firstly, we test the F-B and C-M hypotheses under the two regimes. Secondly, we evaluate the plausible effects of adopting a specific quantitative target on inflation uncertainty. To do this, different GARCH in Mean (GARCH-M) models are constructed to investigate the relationship in two countries with a fixed exchange rate to the US dollar: Jordan and Egypt, and three inflation targeters: South Africa, Brazil and Poland. Note that Egypt has now abandoned the fixed exchange rate system, so the study compares between the time during the fixed system and after abandoning it.The plan of this paper is as follows; section two provides the literature review. Section three discusses the methodology applied. Section four presents the data and country selection criteria. The results and concluding remarks are provided in sections five and six, respectively.It is widely believed that the adverse impact of inflation can be limited if inflation is fully anticipated. This notion indicates that the emphasis should be placed on what makes inflation volatile and unpredictable. Hence, the real costs of inflation should be linked to uncontrolled inflation, which affects both the supply and demand sides of the economy, as implied by . Due to Some policy makers and economists suggest that the costs of a predictable low and moderate inflation rate are acceptable and supported by the economic theory. However,  shows thA large number of empirical works have attempted to examine the nexus between inflation and inflation uncertainty using different measures of inflation uncertainty.  and 25]25] studyAlthough the survey-based measures were believed to be good proxies for inflation uncertainty, such measures were unable to distinguish between transitory and permanent shocks to inflation, where the latter has a much stronger effect on the intertemporal decision making of individuals and businesses. Thus,  claim th construcOne drawback of the GARCH model is that it is unable by its construction to capture asymmetric responses to positive and negative shocks to inflation. Hence a new family of asymmetric GARCH models has evolved to consider the fact that bad news in financial markets has deeper effects than good news . SubsequA few studies have applied the Markov regime switching AutoRegressive Heteroscedastic (SWARCH) model to take account of shifts in the monetary regime in investigating the relationship between inflation and inflation uncertainty. For Peru,  show thaIn fact, the adoption of inflation targeting across many developed and developing central banks has increased the appetite to discover the benefits of the new framework.  suggestsGARCH-type models have been widely employed to investigate the relationship between inflation and inflation uncertainty, as they provide a time-varying measure for volatility. Nevertheless, a standard GARCH model does not allow examining the effects of inflation and inflation uncertainty simultaneously. Hence, the previous statistical technique to study the direction of the nexus, conducted by some studies, was a two-stage approach, where the conditional variance of inflation is estimated in the first stage before performing the Granger causality tests to determine the direction of causality.However, the GARCH in mean model, developed by , permitsThe mean equation:πt−i is the lagged inflation rate; εt−j is the lagged errors and εt is the error term, which has conditional and unconditional mean of zero and conditional variance, ht, given by t−1, which includes only lags of inflation. Stationarity restrictions of the model entail that αi and βj, the non-negative parameters, must be less that unity. If the sum of the parameters is equal to one, the conditional variance must be modelled by Integrated GARCH ..9]. FurtJordan:Egypt:South Africa:Brazil:Poland:δ1 = δ2 = 0. For each country, Chi-square statistics reject the hypothesis that the dummies are zero at 1% level of significance, as shown in the last row of Tables δ2, appear with a negative sign. A large body of literature has pointed out that IT helps countries with their disinflationary efforts, stabilises inflationary expectations and enhances the monetary authority’s accountability and transparency, see for example , , , [, [δ1 = δ example . This, h1, employed in the variance equation, is significant and negative in all the respective countries; however, the magnitude of the effect is negligible for Egypt. Note that this ignores the models estimated for Egypt and Jordan with slope political dummy and regime constant dummy. Nevertheless, this result shows that both regimes could to a certain extent reduce inflation uncertainty, albeit not directly, via decreasing the mean of inflation for FER targeters.The parameter estimates of the inflation uncertainty proxy, incorporated in the mean equation, have a significantly positive sign for all the countries, indicating that inflation uncertainty increases inflation, as argued by C-M. On the other hand, we find support for the F-B hypothesis; inflation does generate inflation uncertainty, irrespective of the regime followed. Remarkably, the coefficient of the inflation regime slope dummy, λβ2 for Egypt, presented in the second column, EGARCH, of 1, incorporated in the mean equation, remains negative for all the countries after controlling for asymmetries. Even when CGARCH-M is used in modelling the inflation variance, the slope dummy has a significantly negative sign for all the countries, except for South Africa, where the dummy turns insignificant. This finding suggests that FER system and IT alike are effective in reducing inflation uncertainty in the long run. Generally, the inflation trend of the ITers approaches the mean quicker than that of the FER targeting countries. The power of the short-run component of inflation uncertainty is also higher in the FER targeters. The diagnostic statistics, reported below for each estimated GARCH model, from Tables st and 12th lag order of Ljung-Box and the 12th lag squared residuals, as well as the LM test for ARCH, suggest neither remaining autocorrelation nor a non-constant variance for all the countries, except for Poland, where ARCH effect remains in the error terms. Poland adopted different monetary regimes during the 1990s. Moreover, [For Jordan, the results imply that both negative and positive inflation shocks have the same influence on inflation uncertainty. The positive and significant oreover,  find thaThe findings of a positive bi-directional relationship between inflation and inflation uncertainty suggest the need for a monetary anchor to reduce both inflation and inflation uncertainty. In general, inflation targeting countries enjoy lower average inflation and inflation persistence compared to the time before adopting IT and compared to the countries with FER regimes. The two monetary regimes appear effective in reducing inflation uncertainty, even under the presence of asymmetries in some cases, like Brazil and Egypt. The effect also remains in the long run, except for South Africa.For FER countries, the benefits of the regime are not reflected in lower average inflation and inflation inertia. The constant regime dummy variable, incorporated in the mean equation, is found to be insignificant for Jordan and positive for Egypt, and although the FER system appears effective in reducing inflation uncertainty, the magnitude of the regime dummy coefficient is close to zero for Egypt. It could be argued that anchoring the exchange rate could still influence inflation uncertainty as long as the possibility to renege on FER commitment is not perceived by the market. Several depreciations in the Egyptian Pound affected the mechanism of the FER system and its credibility in the market. Weak economic institutions and dependency on political authority due to the absence of mutual and clear division between the central bank and government might hamper the role of the FER as a device for decreasing inflation and inflation uncertainty. It could be argued that providing the market with a quantitative target for the price stability objective would not be optimal if it were not accompanied with a clear framework for the central bank’s roles and objectives, the features which distinguish the IT framework.The results provide evidence, represented by lower inflation and inflation persistence for inflation targeting countries, that the IT framework which has a direct quantitative target of inflation could be a better signalling device than the soft peg. The institutional features which accompany adopting IT might help the economy to move from high inflation to low inflation levels, as the credibility of the system, and thereby the policy outcome, hinges upon the development of monetary constitutions and transparent policies. The differences in such institutional arrangements might explain why the advantages of the monetary framework differ across countries.The current paper examines the relationship between inflation and inflation uncertainty in inflation targeting and exchange rate targeting countries and highlights the role of each monetary anchor in reducing inflation uncertainty. In particular, the paper attempts to underline the impact of monetary policy regimes on inflation and inflation uncertainty using GARCH models over the span 01:1980-06:2014.The results from the OLS of the conditional mean of inflation, run to the time before and after adopting the examined regime, reveal that inflation targeters, unlike fixed exchange rate countries, have experienced stable inflation after IT. This is confirmed by the statistics of average inflation, in which the ITers have enjoyed lower average inflation after shifting to IT; such desirable effects are not found for exchange rate targeters. This highlights the importance for our target countries, and in general for structurally similar countries, to move to IT if the target is to reduce inflation and inflation volatility.According to our results, inflation targeting appears to be more effective in lowering inflation persistence and inflation uncertainty than the soft fixed exchange rate regime. However, it is also shown that ITers have not equally benefited from IT. One possible explanation for this might be institutional differences among countries in terms of the level of central bank independence and transparency. Note that countries under the fixed exchange rate lose monetary freedom, as they have to keep their monetary policies in tune with the base country, but they can still ensure institutional independence from the political authorities.In general, the study has made a way towards enhancing the understanding of the effectiveness of announcing an explicit quantitative target on inflation uncertainty. Furthermore, the positive relationship found between inflation and inflation uncertainty in both directions underlines that a monetary regime with an ultimate goal of price stability is a necessity to keep inflation and inflation uncertainty constrained. Additionally, our findings add to the growing body of literature on the importance of inflation targeting as a framework for monetary policy. IT, according to our results, appears effective in lowering the inflation persistence and inflation uncertainty more than the soft fixed exchange rate regime. However, it is shown that ITers have not equally benefited from IT. One possible explanation for this might be due to the institutional differences among countries in terms of the level of central bank independence and transparency. Therefore, for further contributions, it would be of important interest to analyse the plausible impacts of independent monetary practices and constitutions on inflation and inflation uncertainty, under the two regimes, since exchange rate fixers usually enjoy less institutional and economic independence.The countries ranked higher based upon the institutional criteria appear to benefit more from the quantitative target policy. This stresses that announcing a quantitative target without a strong, stable and reliable central bank constitution and deeds does not guarantee achieving low inflation and inflation uncertainty. Given this, the preconditions for adopting IT may play a central role in maximising the benefits of adopting a quantitative monetary policy which have important effects on economic welfare.


An increasing number of innovative oncology monoclonal antibodies (mAbs) have been introduced into the global market, and biosimilar versions have now also been approved in Europe. Being complex to develop and difficult to manufacture, the biosimilar is a drug similar but not identical in physicochemical characteristics, efficacy, and safety to an original biological drug already approved in the European Union, for which marketing exclusivity rights have expired. Generally, the safety monitoring of biosimilars follows the same requirements that apply to all biologicals, even if specific pharmacovigilance measures exist and some of them are still being debated. The manufacturing process, immunogenicity, traceability, and extrapolation of indication are keywords which may impact on the achievement of additional knowledge about the safety of a biosimilar mAb. In this article, we aim to discuss elements that play a central role in the pharmacovigilance legislation of biosimilar mAbs. According to the Directive 2001/83/EC [Biological products are complex structures because of their basic protein structure and other modifications that they undergo during their maturation, generating a complex mix of the same protein under various isoforms (referred sometimes as originator or reference drug) already authorized in the European Union with demonstrated similarity in physicochemical characteristics, efficacy, and safety, based on a comprehensive comparability exercise [A biosimilar is a version of a biological medicinal product   and Colony Stimulating Factors (CSFs)  and recently, the market is affected by the arrival of biosimilars of monoclonal antibodies (mAbs)  must follow all requirements contained in the Directive 2001/83/EC [originator in terms of quality, efficacy, and safety in accordance with the comprehensive comparability exercise.The biosimilar’s MA is based on the demonstration of biosimilarity with its originator. The first step is based on comparative quality studies . These studies, essential for abridging the non-clinical and clinical studies, are the most sensitive to detect differences between the biosimilar and its originator. Non-clinical studies (the second step) are pharmacodynamic and toxicology studies. The backbone of the second step is characterized essentially by in vitro studies. The last step are the comparative clinical studies, whose purpose is to confirm biosimilarity and to exclude any clinically relevant difference in terms of efficacy and safety.The comparability exercise is a step-wise process which consists of a series of head-to-head comparability studies of the biosimilar with its Generally, non-clinical studies are always required by regulators and their extent is tailored to biosimilar’s characteristics. Clinical studies might be waved where such studies may be considered unnecessary. However, as expected for complex molecules as mAbs, non-clinical and clinical studies should always be conducted.Regarding safety, pharmacovigilance is fundamental to obtain additional data on the safety profile of an anticancer biosimilar mAb in the real-world setting.All biosimilar medicines follow the same requirements that apply to all biological medicines, based primarily on Good Pharmacovigilance Practices (GVP) . The MarThe RMP part III is particularly important; it consists of the Pharmacovigilance plan to identify whether, and which, routine or additional pharmacovigilance activities are needed.Routine pharmacovigilance is the primary minimum set of activities required for all medicinal products accordingly to obligations set out by the Regulation (EC) No 726/2004 [The most important activities of routine pharmacovigilance are Adverse Drug Reactions (ADRs) reporting and signal detection. As part of routine pharmacovigilance, MAHs/applicants must collect all reports of suspected ADRs and submit Periodic Safety Update Reports (PSURs) to regulators.reference mAb, it could be also requested for the biosimilar mAb. Other examples of additional PV activities are the use of patients registries or additional long-term immunogenicity data.When necessary, the EMA or a national competent authority may impose on the MAH/applicant additional pharmacovigilance activities. These are non-routine measures or activities performed to provide additional information about the long-term safety profile of a medicinal product or to investigate a safety concern. Examples of additional pharmacovigilance activities are the Post-Authorisation Safety Studies (PASS), which may be clinical, non-clinical, or observational studies normally conducted after approval of the medicinal product. Normally, if a PASS has been requested for the Finally, biosimilars, as well as all biological medicines approved after the 1st January 2011, are subject to additional monitoring and they are included in the ‘List of Drugs Subject to Additional Monitoring’. This means that these medicines are being monitored particularly closely by regulatory authorities after their approval or during a particular time of their life-cycle. A black triangle symbol displayed in the Summary of Product Characteristics (SPCs) identifies all medicinal products inserted in the list. When further studies confirm that the product has a favourable risk-benefit balance, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) removes it from the list.Intra, a pre-change product versus a post- change product (for example among different batches of the same product). Intra changes are related to the choice of cell line, fermentation, purification, and the formulation and they can determinate some differences between different batches of the final product.Inter, a manufacturer A-product versus a manufacturer B-product. Inter changes are based on the fact that the development of a biosimilar requires the establishment of a new manufacturing process because there is usually no direct access to originator companies’ proprietary data.Unlike chemically synthesized medicines, biological medicinal products (biosimilars included) are complex structures and manufacturing changes happen frequently both for originators and for biosimilars. A change can be defined as:the originator, then it has to do a sort of ‘reverse engineering’, and finally to manufacture a product which is as closest as possible with the originator.The biosimilar company has to characterize as much as possible the originator). The complex manufacturing process and intra/inter changes can affect the drug’s safety, quality and efficacy profile. Therefore, the EMA obliges the MAH/applicant to test the pre-version and the post-version of the product to demonstrate that both efficacy and safety remain the same, before and after the change.In the field of biological medicinal products, it is commonly said that ‘the process makes the product’since the biosimilar is defined by its manufacturing process specific to the active substance and to the finished product .In fact, as immunogenicity could depend on several factors related to the manufacturing process, patient’s characteristics, disease, and treatment, data available at the time of approval for a biosimilar may not be sufficient to robustly assess the safety and its correlation to clinical outcomes. Therefore, some adverse reactions and risks (immunogenicity included) will only be discovered in the post-authorisation phase, improving the detection of new signals of harm for patients. For this reason, the risk of immunogenicity of a biosimilar is assessed in relation to the totality of evidence.Extrapolation of indications is a well-accepted regulatory and scientific principle of biological development, and an extensive experience has been gained with biosimilars of ESAs and CSFs. A lot of experience on extrapolation of indication has also been obtained for mAbs in other indication.originator has been convincingly demonstrated and scientifically justified in a key indication. This means that key features of the biosimilar  have shown a ‘high similarity’ with those of the reference product, and so efficacy and safety data can be expected to be the same.The efficacy and safety data extrapolation to other indications of the reference mAb, not studied during development, is possible when the similarity with the reference.Sometimes all these features are not always well-known or completely defined for anticancer biosimilar mAbs. As reported by Cortés et al. , it is noriginator, on the available scientific literature, and on the totality of data obtained through the comparability exercise.Therefore, the concept of extrapolation of indications in the context of biosimilar mAbs is not automatic and it requires always a case-by-case evaluation, based on clinical experience gained on the Traceability is essential to better know ADRs history and chronology. The risks due to a heterogeneous and undefined European policy regarding biosimilars’ switching, make traceability of fundamental importance.Klein et al.  report tFurthermore, the current terminology for ADRs reporting has no appropriate MedDRA coding  for ADRsoriginator. Some producers use the same INN, others a different INN (e.g. epoetin zeta) and all these options are not in contradiction with the European regulation.Also, the naming can have important implications for traceability and safety monitoring for biosimilar mAbs. The most appropriate naming convention for biologics has been an area of significant debate. The international non-proprietary name (INN) fills in the need of a scientific nomenclature of molecules, that identifies them in an unequivocal and neutral way on an international level. When the molecule is not protected by a patent, the INN may be used by all producers competing on the market, associated with their own brand name. However, bearing the same INN does not mean the same thing in the field of biologicals. The EMA has not expressed any position concerning biosimilars’ naming: the biosimilar’s producer may use or not the same INN as the originator, and this could be a problem for communications with Pharmacovigilance network. The unique identification of a biosimilar has a paramount importance to ensure the traceability of the medication in order to avoid compromising signal detection in pharmacovigilance [As many reports described INN, is not always possible to distinguish between ADRs reported for the biosimilar and ADRs reported for the igilance .As discussed above, EU regulatory authorities have an extensive experience on biological medicinal products and guidelines are scientifically well-established.Due to the intrinsic and extrinsic complexity of biosimilar mAbs, the compliance with the specific EU regulatory requirements certify the quality, efficacy, and safety of these medicines.A deep knowledge of all these aspects is very important for commissions dealing with hospital formularies, for acquiring a comprehensive information and appropriately conducting the inclusion process of biosimilar mAbs into clinical practice.


Depressive and anxiety disorders are highly prevalent and form a substantial burden for individuals and their family members. A recent study showed that approximately two-thirds of the children of patients with severe depressive and/or anxiety disorders develop one of these disorders themselves before 35 years of age. In the Netherlands, various preventive interventions are available for children of parents with mental illnesses. However, the actual reach of interventions is small . A major barrier appeared to be parents' hesitancy to let children participate in preventive programs. In order to address this barrier, we designed a pilot study to implement a psychoeducation program on parenting and mental illnesses. The main aim of this study was to investigate how a preventive family-focused approach can be embedded in routine adult psychiatric care. The pilot started in April 2017 and has ended in September 2018. It was conducted in the University Center Psychiatry (UCP) in Groningen, The Netherlands. This article describes the implementation process so far. The main intervention was a monthly organized group-psychoeducation called “parenting and a mental illness,” which could be attended by parents currently treated in the UCP. In 18 months, implementation activities were divided in four phases; (1) Creating awareness, (2) Adoption of the intervention, (3) Implementation and evaluation, and (4) Continuation phase. The program development process was evaluated using both qualitative and quantitative data. Based on the pilot study we were able to make recommendations for the further implementation of this approach so that more parents can be reached in future. Further study with follow-up activities is needed to measure the effects of the psychoeducation, for instance on parenting functioning and the quality of the parent-child interaction. Up to 45% of patients who receive adult psychiatric care are parents . Having In the Netherlands, various interventions for prevention of mental health problems in offspring of depressive and anxious adults have been developed. Current interventions are aiming at the parents (psycho-education and parenting skills), the children , or the family as a whole  , 5.However, the vast majority of children and parents does not receive the services they require . RegardiA first and crucial step in increasing the range of participants in preventive interventions is to get the offspring in the picture. A substantial group of these high-risk children can easily be detected; namely through the parent being treated. van Doesum et al.  found thHowever, Skogøy et al.  underlinProfessionals may perceive talking about parenthood with their patients as a sensitive topic , 14–16. How can a preventive family-focused approach be made feasible and acceptable, for parents and professionals?Which remedies can be identified in order to increase feasibility and acceptability?Which recommendations can be given to further implement this approach?The main aim of this pilot study was to investigate how a preventive family-focused approach can be embedded in routine adult psychiatric care. This aim resulted in the following research questions:We designed a pilot study to implement a preventive, family-focused approach for adult patients treated for depressive and/or anxiety disorders. We tried to build on existing routines so that changes were kept as small as possible. In the University Center Psychiatry (UCP) a psychoeducation program for parents already existed for a few years, but the program was not offered on a structured base, i.e., at maximum three to four times a year, at different times and dependent on the number of parents staying in the inpatient ward. A social worker of the inpatient ward coordinated these sessions and any other actions for patients regarding their children. Also, she led a special working group of professionals. Nurses were used to refer to this social worker, who invited parents to talk about the impact of parents' illness and to help explain the situation to children, on an age appropriate level.In a four-phase implementation plan, we worked toward a situation in which all professionals mention patient's role as a parent at least once during routine treatment, and motivate parents to attend the group-psychoeducation “parenting and a mental illness” which was now offered monthly. Since it is known that parents may perceive different kinds of barriers to participate in preventive interventions, we listed common barriers and made a plan to address them in this pilot study .The medical ethical committee of the University Medical Center Groningen evaluated this study as not falling under the Medical Research Involving Human Subjects Act (WMO). Nevertheless, we followed the required procedures and obtained written informed consent for the qualitative components of the project. No written informed consent was requested for participation in a psychoeducation meeting because this option was offered as part of the treatment. Patients knew that their own therapist would be informed of their participation. Collection of participant information was kept to a minimum and reported at group level, such as the number of participants who joined the psychoeducation. In (online) registration the current privacy legislation was followed and only the necessary information was requested, such as an e-mail address confirming the registration, and the age category of the children to adjust the psycho-education on that particular evening.The target group consisted of adult patients who are parents of children in the age range of zero till 24 and who are currently being treated for depressive and/or anxiety disorders in an outpatient or inpatient ward. Patients will be informed by their own practitioner , social workers, and/or nurses of the inpatient wards. The participating wards are one outpatient ward and two inpatient wards for patients with depressive disorders, 2 day-clinics for depressive disorders, one outpatient ward for bipolar disorders, an outpatient ward for anxiety disorders, and a day-clinic for anxiety disorders. Since the UCP is a tertiary care center, symptom severity of most patients is moderate to very severe.In 1 year about 1,200 adult patients with depressive and/or anxiety disorders are treated in the UCP. It has been estimated that 30–50% of these patients have children. Systematically, information on the parent status of a patient is gathered when patients enter the UCP to receive care, via a general questionnaire. In this way practitioners know by forehand (a) whether the new patient is a parent, (b) how many children he or she has, and (c) what the age of the children is.Practitioners and/or nurses mention patient's role as a parent at least once during routine treatment, and motivate parents to attend the group-psychoeducation “parenting and a mental illness.”Psychoeducation meetings for patient-parents are offered on a regular base.We examined possibilities to permanently embed the preventive, family-focused approach in the organization and management structures.We performed this pilot to investigate the possibilities to permanently embed a preventive, family-focused approach in routine treatment protocols. In concrete terms, this meant that:Patients introduce themselves shortly , followed by an introduction to the theme parenting and a mental illness. In particular, attention is paid to illness perception and the relation with the patient's role as a parent, before and during treatment. Group leaders pay attention to feelings of guilt or shame that may be present regarding shortcomings in the parenting role. Furthermore, the role of the other parent is a topic of conversation.How do parents tell their children about mental illness? This starts as an open conversation in which parents share their experiences. Later, group leaders give a summary and provide examples of how to talk with children about their mental illness, using age-appropriate information. Group leaders may notice barriers in talking with their children among parents, for example not wanting to bother their children and bring up these subjects.How do parents know when it is (not) going well with their children? Do they have worries about their children's wellbeing? For each age category, the group leaders provide information on signals of (ab)normal development. Sharing of experiences among parents is encouraged.We organized a monthly group-psychoeducation, on every first Thursday evening of the month, called “parenting and a mental illness.” An experienced social worker of the inpatient ward for depressive disorders of the UCP and a child psychologist gave the psychoeducation, using a power point presentation. Project leader MP (resident psychiatry) coordinated applications for the evenings and was available to stand in when one of the group leaders was hindered to give the psychoeducation. Patients attended one meeting and were encouraged to bring their partners. The psychoeducation could only be attended by parents currently treated in the UCP. The content of the psychoeducation was theory-based and consisted of the following main items:Additionally, at the end of the psychoeducation meeting further supportive options were offered to the parents, such as continued conversations about parenting with their current practitioner, or other professionals . If necessary, referral of the child for child psychiatric consultation was offered.We estimated that 68 parents would have attended the group-psychoeducation after 1 year, based on data that about 1,200 patients with a depressive and/or anxiety disorder are treated in the UCP in a year. About 480 of the patients have children (40%) and we estimated that 336 parents could be motivated by practitioners to join the psychoeducation, with an eventual reach of 20% of the motivated parents.The pilot study started in April 2017 and was planned to end at the end of September 2018. In this time span of 18 months, implementation activities were divided in four phases; (1) Creating awareness, (2) Adoption of the intervention, (3) Implementation and evaluation (following an iterative process), and (4) Continuation phase. We described intended activities in these four phases in our implementation plan that we wrote prior to the start of the project. The implementation plan, including the four phases, was based on a workbook for guideline implementation in youth help and protection services  attended the regular team meetings of all participating wards, to discuss with colleagues how the family-focused approach could be embedded in their ward. In addition, these meetings served to spread flyers with practical information about the project and to present a flow chart of general procedures regarding children of patients and child safety. At the launch of the actual implementation (September 2017), more information on the project was given in a presentation for all professionals and researchers in the UCP. We stressed that the primary aim of the project was to pay more attention to patients' normal role as a parent, for example by asking how parents manage to perform this role now they are being treated for a mental illness. Existing child safety procedures were mentioned, but were not the main focus of the project.https://kopp.umcg.nl that we had developed in this first phase of the implementation. The launch of the project (including the infographic) was also spread as a local news item by the press agency of the UMCG, among others via Facebook. On the project website, more information was provided regarding the monthly group-psychoeducation on parenting and a mental illness. Recently, the infographic was translated to an English version which can be found via the following link https://www.youtube.com/watch?v=mZbsXjh2hYM.Finally, we created awareness for the importance of implementing a preventive, family-focused approach. For both parents and professionals, we developed an infographic film of 3 min illustrating the impact on the family when one of the parents has a mental illness. This infographic was placed on the project website This phase predominantly focused on activities that promoted the adoption of the intervention, such as creating awareness and support of various groups, including the management.First, via a survey among professionals of the department mood and anxiety disorders, we inventoried general practices regarding the attention for patients' role as a parent in routine treatment protocols. This raised awareness among participants and gave us an impression of the current state of preventive, family-focused care at the department. Second, in order to gain broad support for the project, we organized participation meetings with the client counsel, social workers, residents, the secretaries, and managers of the department. About once in 3 months, we wrote an update of the implementation process to publish in the UCP newsletter.From September 2017 on it was possible to sign up for the group-psychoeducation sessions. Both parents themselves and practitioners were able to sign up, online via the project website, via an email or via a registration form on paper. The first psychoeducation session took place on the first Thursday in October 2017. After the start of the psychoeducation sessions, we constantly adjusted the original implementation plan to the actual situation in clinical practice, using an iterative approach. Feedback of parents and practitioners was essential during this phase. For example, after introducing the pilot project, the importance of the topic “parenting and a mental illness” was endorsed by many professionals. However, some of them indicated that they had not enough time to discuss parenting in the treatment sessions within the scheduled time. To solve this problem, we suggested that they could use the infographic film of 3 min to introduce the topic and refer parents to the group-psychoeducation. Another example of a change in the initial plan was prompted by the observed difference in working methods at the various wards. By attending team meetings of the wards, we explored together with the professionals how the family-focused approach could best fit the current working methods in their opinion. Furthermore, parents were asked to fill out a feedback form after attending a meeting  and someParallel to the implementation of the family-focused approach, the experiences of nurses with talking about parenting were investigated by students of the School of Nursing (University of Applied sciences). They performed two qualitative research projects, in which nurses were interviewed both individually and in focus groups . For the interviews, topic lists on the theme parenting were used. With respect to the aim of this study, we do not extensively report on the nursing projects in this article. However, these projects may have contributed to increased awareness of parenting and continued positive reinforcement. In general, nurses were highly motivated to participate in the interviews and brought up some interesting topics, such as task ambivalence. On the one hand they felt family-focused care as one of their core responsibilities, but on the other hand, many nurses found it unclear when and how specific tasks should be performed and by which professional.The main goals of this final phase of the implementation were (a) to create support and guidance for the intervention in the organization and management structures, (b) to realize professional guidance on the work floor and/or training, and (c) to make arrangements with management and stakeholders for continuation of the project. To date, we have taken the following steps. First, we have developed the parental questionnaire “parenting and a mental illness,” involving questions on experiences of patients' role as a parent and wellbeing of the children . The reaThe implementation was evaluated using both quantitative and qualitative data. The quantitative part consisted of a survey among professionals of the department of mood and anxiety disorders and registration of the number of participants at the monthly group-psychoeducation meetings. The online survey  was creaThe qualitative part consisted of written evaluation forms of the psychoeducation meetings (filled out by parents) and semi-structured telephone interviews with some of the parents who participated in a psychoeducation meeting. Questions asked were for example: “What was the most positive of the evening and what are you least satisfied with?” and “Do you have any suggestions for us to improve this psycho-education?”Lastly, we reflected on the barriers that we had listed, whether and how we addressed them and which remedies were found .In September 2017, at the launch of the implementation, we performed a survey among professionals of the department of mood and anxiety disorders. All professionals received an email with a link to the online survey which consisted of ten multiple choice questions about the general way of practice regarding family-focused care. Thirty-two professionals filled out the survey in a time span of 6 weeks. Most of them were nurses (13/32), followed by psychologists (7/32) and other professionals, such as creative therapists (5/21). Furthermore, three psychiatrists and four residents in psychiatry filled out the survey. Respondents were about equally spread among the different wards of the department of mood and anxiety disorders; professionals from the inpatient wards (12), the day-clinic wards (11), and the outpatient wards (13) were represented. Some professionals worked at more than one ward. Nineteen of the 32 respondents (59.4%) answered that they mostly or always mention parenthood when they talk to patients who have children in the age of 0–24 years. The other 13 respondents answered they do not mention the topic regularly. Regarding the timing for bringing up the topic, most respondents thought the beginning of treatment (until the third meeting with the parent) is most suitable. Although most professionals said to talk about parenting and/or child wellbeing, they indicate a need for further education or skills training in their current work. Eleven professionals want to have more general information on mental illness and parenthood; for example on the actual risk that children will develop problems if their parents have a mental illness. Furthermore, 19 professionals indicate that they miss practical information, such as to which organization they can refer parents and/or children if they signal any problems. Finally, skills training in conducting conversations about parenting and child wellbeing is wanted, as indicated by 11 professionals.In At the end of the psychoeducation meetings, we asked participants to fill out an evaluation form in which we asked whether parents regarded the meeting as useful and which needs they had regarding parenting and wellbeing of the children. Twenty-five participants filled out the evaluation form. All regarded the meeting as useful. Most of them further commented on this question, as shown in In addition, we interviewed four participants by telephone after they had attended a group-psychoeducation session. The participants who were interviewed concerned one woman who had been treated for depression and her husband and two women who were partners of patients in care. Beforehand they all consented to be interviewed about their experiences. All four were positive about the organization and contents of the evening. Exchange of experiences was mostly appreciated, although sometimes confrontational, for example when it appeared that other participants had received more familial support than the respondent. The timing  was seen as very important. Recommendations on which words to use to explain about the mental illness to their children were appreciated. One of the respondents suggested that this meeting should be mandatory for all patients with children.In this pilot study, we have described the development of a program to implement a preventive family-focused approach into routine care for adult patients who are parents and treated for moderate to severe depressive and/or anxiety disorders. The focus was on feasibility and acceptability. Most professionals expressed their sympathy to the project. Our survey showed that professionals consider it as important to inform patients who are parents about the possible impact of mental illness on parenting . The other 40% did not mention the topic frequently, and the need for additional training (education and/or skills) was indicated by a majority of professionals.Team discussions revealed that opinions differed between disciplines whether talking about parenthood was part of their job. At wards where a social worker was part of the team, patients were preferably referred to the social worker for further consultation. However, the option of referral to a social worker is not present at all wards of the UCP. It gradually became clear that the family-focused approach fitted very well with the core business of nurses. First of all, the survey was filled out by nurses for 41% 13/32). This fits with literature on this topic, which shows that nurses are in a unique position to initiate conversations on parenthood and child wellbeing because of their direct, frequent, and sustained contact with patients and families . Neverth/32. ThisAs Foster and Isobel  have poiThe monthly organized psychoeducation meetings for parents were visited by 64 parents in 1 year. By far most of them (38) applied via the online registration form on the project website. Parents' reactions after the psychoeducational meetings were mainly positive, and they provided useful feedback to further improve the meetings. A good timing of the psychoeducation, for instance, was deemed indispensable. Parents' reactions were discussed in the team meetings by the project leader and once more colleagues were asked to draw their patients' attention (on time) to the educational evenings. This illustrates that the implementation of a preventive approach is not achieved after one or two actions, but requires continuous positive reinforcement .The number of parents participating in the monthly psychoeducation meetings was variable. More professionals started to refer parents, but the most visible increase in registrations was in the number of parents who applied directly via the website. This may indicate that the psychoeducation meets the needs of, at least a subset of parents treated in the UCP, which also corresponds with the positive feedback of parents who had joined a psychoeducation meeting: all regarded the meeting as useful, and about half of the parents would like further support. Furthermore, feedback and interviews indicated that awareness among parents about the impact of the mental illness on child wellbeing has grown. We think that for e.g., better provision of information about the preventive offer may have facilitated parents to be more aware and to participate in the psychoeducation. Furthermore, the easy way of registration may also explain the higher number of online applications, or the fact that the involvement of a (busy) professional can be avoided.A limitation of our research is that it was carried out in a specific setting under specific circumstances. It is unlikely that the same circumstances are present in any other organization for adult care, which could result in different outcomes. On the other hand, a strength of this pilot is that we were able to demonstrate how an iterative implementation method can be used to realize a translation from current knowledge to clinical practice. Further prospective studies with a control group are needed to assess whether preventive psychoeducation, as part of a family-focused approach, is effective. Findings of this pilot study provide useful information for setting up larger studies with a higher impact. Our aim is to continue the psychoeducation program in the UCP and to further develop it, using the outcomes of this pilot study. Regarding policy, we strive to offer more parents the possibility to attend the psychoeducation meeting on parenting and a mental illness at the UCP, for example by sharing our knowledge with other health care providers and governmental organizations.In conclusion, our findings indicate that our preventive family-focused intervention met the needs of parents that participated in the psychoeducation meetings. Feedback of participants showed that they regarded the evening as useful, and more importantly, they seemed to be more aware of the potential impact of their illness on their children. However, a large number of parents were still not reached by our intervention and further study with follow-up activities are needed to measure the effects of psychoeducation on, for example, parenting, the quality of the parent-child interaction and child wellbeing. Lastly, we regard the structural embedment of interventions and continued positive reinforcement as essential elements for long-lasting attention for the prevention of mental health problems among children of parents that are treated for mental health disorders.MP, LD, and PH set up the project, conducted the pilot study, and wrote the manuscript. CH supervised methodology, RS supervised it all.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Parent carers of disabled children are at increased risk of mental and physical health problems. They often experience challenges to maintaining good health which have implications for their well-being and their ability to care for their children. In response to these needs, researchers and parent carers developed the Healthy Parent Carers (HPC) programme. It is a peer-led, group-based intervention that promotes behaviours associated with health and well-being. The aims of this trial are to assess the acceptability of the HPC programme and the feasibility of its delivery in the community and to assess the feasibility and acceptability of the design of the definitive trial to evaluate the programme’s effectiveness and cost-effectiveness.We will establish six research sites and train facilitators to deliver the manualised intervention. Parent carers of children with special educational needs and disabilities will be individually randomised, stratified by group delivery site, to either take part in a group programme and online resources (intervention) or to receive access to the online resources only (control). Measures of mental health; well-being; health-related quality of life; health behaviours; patient activation; protective factors such as resilience, social connections, and practical support; and use of health care, social care, and wider societal resources will be collected before randomisation (baseline), immediately post-intervention, and 6 months later. Recruitment of participants, adherence to the programme, and the dose received will be assessed. Group sessions will be audio-recorded to evaluate the fidelity of delivery and participant engagement. Participants’ and facilitators’ feedback on the programme content and delivery, their experience, and the acceptability of the outcome measures and trial design will be collected through feedback forms, interviews, and focus groups.This trial will assess whether the programme delivery and evaluative trial design are feasible, to inform whether to progress to a definitive randomised controlled trial to test the effectiveness and cost-effectiveness of the Healthy Parent Carers programme.ISRCTN151144652, registered on 25 October 2018; ClinicalTrials.gov, NCT03705221, registered on 15 October 2018.ISRCTN,  There are an estimated 960,000 disabled children in the UK, which is 7.3% of the population of children aged 0–18 years –11 and pParent carers often find the demands of caregiving have a negative impact on their physical and emotional health. Nevertheless, it is important to acknowledge that not all parents of disabled children report that their child’s difficulties negatively affect their psychological or physical health , and in Some interventions target external factors, such as navigating healthcare services , while oThe idea for this research came directly from parent carers who had been involved in a study evaluating peer support for parent carers . They waPreviously, we tested the principle and acceptability of a 6-week intervention programme with one group of seven parent carers, delivered by the intervention developers. The intervention was developed using Intervention Mapping  and exteTo determine whether the peer-led, group-based HPC programme is more effective at improving health and well-being compared to providing online information onlyTo estimate the costs of delivering the HPC programme, and the cost-effectiveness of the programme, versus the provision of online informationTo understand how the Healthy Parent Carers intervention is working, for whom, and in what context to inform the implementation of the programme should it be shown to be effectiveThis feasibility trial will provide information that will be used to determine whether to progress to a definitive trial of the HPC programme, which would have the following objectives:The current trial aims to assess the acceptability of the HPC programme and the feasibility of its delivery in the community, as well as the feasibility and acceptability of the design of the definitive trial in order to evaluate whether a fully powered randomised controlled trial is warranted and to determine the optimal trial design.Assess the feasibility of establishing venues, and identifying and training group facilitators to be in a position to deliver the interventionAssess the fidelity of intervention delivery in terms of format, content, and qualityAssess the experience and engagement of participants, facilitators, and trainersAssess the programme attendanceTo evaluate whether the programme can be delivered in the community by facilitators other than the developers, specifically to:Assess the feasibility of recruiting participants in different sitesAssess the acceptability of randomisation of parent carersAssess the attrition and completion and proportion of any missing data in questionnaire measuresAppraise the performance of candidate health and well-being outcome measures in terms of acceptability to participants, and feasibility and interpretability for researchersEstimate the variability (standard deviation) and the level of clustering within programme delivery groups in the intervention arm to help inform the sample size calculation for the definitive trialTest the proposed cost-effectiveness framework for a future randomised trialTo provide information necessary to design a definitive randomised controlled trial, specifically to:This trial has two overarching aims:This will help inform whether to progress to a definitive randomised controlled trial to test the effectiveness and cost-effectiveness of the programme and provide information necessary to design the trial.A feasibility trial using a parallel group randomised controlled trial design will be carried out in six sites in the southwest of England. Participants will be randomly allocated to receive the group-based programme and access to online programme resources or to a control group receiving access to the online resources only. Data collection will take place at three time points in both trial arms at baseline (prior to randomisation), immediately post-intervention, and 6 months later. As the intervention can be delivered over 6 or 12 weeks, the post-intervention data collection time point will vary relative to randomisation but will be consistent in terms of the amount of time passing after completion of the intervention. Participants in the control arm in each randomised site will complete measures at the same time as participants in the intervention arm for that site. The two arms will therefore be balanced in terms of the timing of outcome measures. The trial design and the flow of participants through the trial are illustrated in the trial flow chart and SPIRIT figure  the research is conducted in an acceptable manner, (b) the research outputs are relevant and useful to parents of children with special educational needs and disabilities, and (c) our dissemination materials and methods are appropriate and accessible.Over 40 parents of children with a range of conditions from the PenCRU Family Faculty public involvement group have participated in a study-specific working group since 2014. Our Stakeholder Advisory Group (SAG) includes representatives from the local authority, public health, parent carer forums, relevant charities, and special schools.Proposing the idea for the project based on their needs and experiencesCo-designing and refining the intervention and training content and delivery methodsProviding feedback on research methods including the selection of the comparison conditionsAdvising on the content and form of the Resource Use Questionnaire for use as part of the cost-effectiveness frameworkContributing to interpreting and disseminating the findings of the previous studyInterviewing and hiring research staffDiscussing and advising on the design of the feasibility trialRecommending responses to peer reviews when applying for funding.Parent carers have been involved in all stages of developing the intervention and designing the feasibility trial including:In collaboration with our SAG, we will identify six venues  where it is possible to establish and host a group. We will agree days, times, durations and frequencies of sessions, and local named organisers for each venue.—76 participants) with a margin of error of 10 percentage points based on the lower bound of the 95% confidence interval. Assuming that 38 participants are followed up in each trial arm, this will be large enough to estimate the standard deviation for continuous outcomes in each arm within 29% of its true value based on the upper bound of the 95% confidence interval. Finally, 76 participants at follow-up are large enough to estimate a correlation coefficient of 0.5 between baseline and follow-up scores for a continuous outcome with a margin of error of 0.19 based on the lower bound of the 95% confidence interval. We will randomise a minimum of 8 and a maximum of 24 participants at each of the 6 sites. This will mean that 4–12 participants will be allocated to each of the intervention and control trial arms at each site. We expect the ideal group size to be between 6 and 12 people but are allowing for potential attrition and variation in recruitment between sites.We aim to recruit 96 participants, to be allocated on 1:1 ratio to intervention and control. This is a large enough sample to estimate the percentage providing data at follow-up (assumed to be 80%People meeting the inclusion criteria are (1) primary carers of children with additional needs and/or disabilities  legislation in England and The Children’s Act; no named diagnosis is necessary, and we are not limiting to specific conditions), (2) willing and able to attend the programme group meeting session(s) on arranged dates/times, and (3) able to access online information.Potential participants who are not able to communicate in English are excluded. This is necessary because the programme has not yet been translated into other languages.the members to share in their networks. We will liaise with Information and Advice Services in each locality, staff in social services, and Special Educational Needs Coordinator (SENCOs) in schools in each study site to target potentially more isolated parent carers. We will also recruit participants at events for parent carers at the study venues and other venues in the southwest where interested parent carers can discuss the project with the research team. This recruitment strategy uses many different approaches because parent carers do not all access the same services and not all parent carers are connected with their local parent carer forums. We will ask all participants how they heard about the study during screening, and this information will be recorded to assess whether some recruitment methods may be more effective than others. However, we are mindful that while some methods may not result in large numbers of recruits, they may help us to reach parent carers who are more isolated and more in need of support and, as such, will be seen as important methods to take forward in a definitive trial.We will advertise the study in several ways. Press releases and interviews in local television and/or radio will be used to publicise the study. Members of our SAG will be asked to advertise the project to their members through their email lists and networks. We will also share study adverts and information via social media and through the PenCRU Family Faculty email list, asking a telephone or face-to-face screening to check the eligibility, understanding of the study, and to answer any questions. A researcher will meet each potential participant individually. Those who want to participate will sign a consent form and complete baseline questionnaires online using an electronic patient-reported outcome (ePRO) system with a researcher on hand for support as necessary [Interested parent carers will contact the researchers. There will be ecessary . ReasonsWhen recruitment is completed at each site, we will proceed to randomisation. Each of the six programme groups will constitute a study site, with participants who choose that group being randomised to either attend the group or receive the online resources only. A computer-generated randomisation sequence will be used to assign the participants in each site to the intervention and control arms. A block randomisation scheme will be implemented to ensure balance in the number of participants allocated to each trial arm, stratified by group delivery site. The allocation sequence will be concealed from researchers using an online central randomisation service setup and maintained by the Exeter Clinical Trials Unit (UKCRC Registration ID 65). Blinding will not be used in this trial.All participants will receive an email and letter indicating the result of randomisation. The participants randomly allocated to the intervention arm will be sent details of the group sessions and be contacted by their lead facilitator before the first group session. Participants in both arms will receive a link to the online programme resources and instructions on the web page. We will monitor the number of participants who refuse participation and record their reasoning (if they wish to share it) to gauge the acceptability of our trial design.The group-based programme was developed using Intervention Mapping approach . Full deThe programme content is based around a set of universal and evidence-based actions  associated with health and well-being. CLANGERS stands for Connect, Learn, be Active, Notice, Give, Eat well, Relax and Sleep . The ‘CLThe programme content is organised into 12 modules lasting 2 h each. The modules can be delivered weekly over 6 sessions (comprising 2 modules per session) or 12 sessions (1 module per session). Our Family Faculty PPI working group suggested that offering either 6 longer sessions in the daytime or 12 shorter evening sessions would be reasonable for most parent carers. One or both options will be offered per area in order to maximise recruitment and to reflect likely real-world delivery in community settings, with 6 groups being delivered in the study in total. If uptake is very low for a particular site, the delivery model may be adapted during recruitment to increase numbers.The lead facilitators of the group-based programme will be experienced facilitators of the ‘Expert Parent Programme’ courses created by the Council for Disabled Children (CDC) with funding from the Department of Health. The facilitators are parent carers. CDC has a selection process, trains, and provides supervision for their facilitators to ensure that they facilitate the groups effectively. Their nationwide network of over 70 facilitators provides a sustainable model for the implementation of the programme in the future. Facilitators will use the Healthy Parent Carers Facilitator Manual that includes module outlines, content, timings, activities, and resources needed. The Facilitator Manual also includes safeguarding procedures for the facilitator to follow in case of any adverse events such as suicidal ideation or disclosure of safeguarding issues.There will also be an assistant facilitator in each group to assist the facilitator in sessions. We will recruit a local parent carer for this role using a person specification detailing the required personal qualities and skills and a selection process.We will provide training for lead and assistant facilitators. The training will take place over 4 days for lead facilitators and 2 days for assistant facilitators; it will be delivered by researchers and the parent carer co-investigators who co-developed the programme and facilitated the group in our previous study. Lead facilitators will receive ongoing supervision and support through the CDC and support from the research team. Conference calls with facilitators, assistants, and researchers will be convened to reflect on delivery of the sessions. These discussions will inform intervention design and training needs and provide a forum to share ideas and ways to address any challenges arising.The Healthy Parent Carers online resources are part of the intervention. They reflect the content of the group sessions, provide space to write down reflections, and prompts to set specific goals and for self-monitoring of CLANGERS-related behaviours.If the participants in the group programme miss a session, they will be telephoned by the facilitator, who will summarise the session and encourage the participant to reflect on their week, read the section of the HPC online resources, and set their weekly goals.Participants in the control arm will receive access to the HPC programme resources online with instructions. Risk of contamination between participants allocated to each arm is low because the intervention is predicated on participants developing a shared social identity as members of the HPC group. Participants in both arms will be asked whether they have had contact with participants in the other arm of the trial as part of a post-intervention feedback form.We will record the data on the feasibility of recruitment, including how many people respond to the adverts, how they heard about the study, reasons for not taking part for those who decline, and how many are successfully recruited. We will record delivery setting, delivery model, attendance, attrition, and reasons for missed sessions or withdrawal from the study. We will also monitor how long it takes to accrue the target number of participants at each site and at what point in the trial process any participants withdraw.Demographic data will include gender, ethnicity, parent relationship status, number of children, employment status, level of education, income, housing status, and age, gender, and diagnosis (if any) of their disabled child. We will also collect information about their disabled child’s functioning and health complexity using the About my Child measure (AMC-19) . We willParticipants will be asked to complete all measures before randomisation, immediately post-intervention, and 6 months post-intervention, regardless of attendance or engagement with the interventions. Based on the recommendations from our Family Faculty PPI working group, the measures will be available to complete online, using a computer, smartphone, or tablets. The Exeter Clinical Trials Unit will set up an online platform for participants to access and complete the measures. Participants may request to complete the measures on paper if they wish. Any measures completed on paper will be independently double-entered by two researchers. These requests will be monitored to track preferences for online- versus paper-based measures.Two members of our Family Faculty PPI working group have tested the applicability and time to complete the measures (45 min). A £25 shopping voucher will be posted to participants as acknowledgement for completing measures at each time point.Warwick-Edinburgh Mental Well-being Scale (WEMWBS): The WEMWBS is a 14-item scale used to assess the mental well-being in the general population and in the evaluation of programmes aiming to improve mental well-being . ResponsPatient Health Questionnaire-9 (PHQ-9): The PHQ-9 is a 9-item measure that rates the frequency of symptoms and is designed for screening, diagnosing, monitoring, and measuring the severity of depression –39. CateEuroQol 5 Dimensions (EQ-5D-5 L): The EQ-5D-5 L is a measure of health-related quality of life. It consists of five items measuring five dimensions of health-related quality of life  and a vertical visual analogue scale measuring self-rated health . QALY weParents’ Assessment of Protective Factors (PAPF): The PAPF is a 36-item measure that assesses protective factors identified in the development of the Strengthening Families evidence-based parenting programme . These pHealth Promoting Activities Scale (HPAS): The HPAS is an 8-item measure of a person’s estimation of the frequency with which they participate in a range of activities that promote or maintain health and well-being , 45. It Patient Activation Measure (PAM): The PAM is a 13-item measure that measures the spectrum of skills, knowledge, and confidence in patients and captures the extent to which people feel engaged and confident in managing their own health and care , 47. It ICEpop CAPability measure for Adults (ICECAP-A): The ICECAP-A is a 5-item measure of capability, which includes the following aspects of well-being found to be important to adults in the UK: attachment, stability, achievement, enjoyment, and autonomy –50. A seResource use questionnaire: We developed a study-specific resource use questionnaire in collaboration with parent carers. This includes health, social care, participant, and broader societal resource use, and draws on measures in the Database of Instruments for Resource Use Measurement (DIRUM) .The measures will comprise:In line with the MRC guidance on process evaluations, this study will include a process evaluation that is appropriate for the feasibility testing stage of the development-evaluation-implementation process for this intervention . This prFacilitator pre-training questionnaire: We will use a pre-training questionnaire to collect information about facilitators’ characteristics, their motivations to take part, relevant background and experience, and expectations of delivering the programme.Facilitator training feedback: Following delivery of the training, we will use a questionnaire to gather the facilitators’ feedback about their self-reported knowledge, understanding, skills, and confidence to deliver the intervention and to gather their reflections on the training.Facilitator delivery observations: We will use a checklist to assess lead facilitators’ competence to deliver while observing their delivery of the programme content during the facilitator training. The checklist includes key skills and competencies linking to the objectives of the lead facilitator training and will enable trainers and research staff to assess facilitators’ readiness to deliver the programme. This will also help to guide and plan additional or future training.Facilitator checklist, records, and support calls: We will use a self-report checklist completed jointly by the facilitators to indicate which content they have covered in each session (adherence), the duration of the sessions (dose), and the participants’ engagement. Facilitators will be asked to record attendance at each session. We will also arrange support calls with facilitators to gather more information about how the groups are going and any challenges to delivery.n = 6, 14%). The two researchers will compare the scoring of the first three groups immediately, and any inconsistencies will be discussed with JL/MT, to ensure there is a clear understanding of the assessment criteria. The scores of the double-coded sessions will be agreed between researchers, and the sessions assessed by the researchers will be compared with the facilitators’ scores.Session recordings: We will audio-record group sessions and will sample two to three recordings from each group to assess fidelity to intervention content, quality of delivery, and participant engagement. A researcher will rate the delivery using the same checklist used by the facilitators after each session. A second researcher will rate one recording per group  in the intervention arm and 6 participants allocated to the control arm across all sites for semi-structured telephone interviews. For the intervention arm, these interviews will explore participants’ experiences of, and engagement in, the programme and the group and their views on the group content, activities, and facilitators. All, control and intervention groups, participants will be asked in the interviews about engagement with online resources, perceived impact of the programme and any potential contextual influences, and acceptability of the trial processes and measures. We will also sample up to 4 participants (from different groups) who were allocated to the intervention arm of the trial but did not attend any group sessions to ask them about barriers to attending and whether anything could be done to promote attendance in future groups. All interviews with participants will last approximately 30 min and will be audio-recorded and transcribed verbatim, with names and other personal identifying information changed to protect confidentiality. Interviews will take place as soon as possible after the participants have completed their post-intervention measures and before they complete their 6-month follow-up measures.Focus groups with facilitators: We will invite all lead facilitators and assistant facilitators to a focus group after the end of all groups. The focus group (lasting approximately 2 h) will cover facilitators’ experiences of delivering, and engagement with, the programme, views on the programme content, activities and feasibility of programme delivery, facilitator training and skills, group management, and suggestions for improvements. The focus group will be audio-recorded and transcribed verbatim .The following data collection tools will be used to assess fidelity of intervention delivery, participant and trainer characteristics/motivations, trainer knowledge and self-efficacy to deliver the programme, participant engagement with the programme/online materials, and acceptability of the intervention and trial design.Establish methods for estimating intervention resource use and costs , in collaboration with the programme facilitators and site representativesDevelop a resource use questionnaire in collaboration with parent carers, drawing on measures in the Database of Instruments for Resource Use Measurement (DIRUM) repository Assess the acceptability to parent carers of the EQ-5D-5 L, the ICECAP-A, and the WEMWBS, judged by missing data and measurement properties .We will develop and test a framework for assessing the cost-effectiveness of the intervention in a future randomised trial. We will:We will report the number of eligible people who self-refer and the percentage ) of these that are randomised in the trial. These findings will also be reported separately for each type of delivery setting and delivery model to assess whether particular delivery settings or models are more popular and therefore would lead to higher recruitment rates in the subsequent definitive trial. We will also report numbers and percentages of people who heard about the study via different sources, organised into categories.We will also report the percentage  of participants who complete each assessment at each time point as an assessment of the acceptability of the measures and of the feasibility of collecting sufficient data in a definitive trial. We will summarise the characteristics of recruited participants using demographic data to allow for assessment of the representativeness of the sample relative to figures available from the Office for National Statistics on the population in the southwest of England. We will also report the baseline comparability of the trial arms with respect to demographics and outcome measures.For the intervention arm, we will report the number and percentage of participants that attend each group session with 95% confidence intervals. The percentage of participants that are lost to follow-up at each follow-up point will be reported for each trial arm. Select characteristics , and baseline scores on outcomes) will be compared between those who are and are not lost to follow-up within each trial arm using descriptive summaries, but no formal statistical tests. Acceptability, judged by missing data of EQ-5D-5 L and ICECAP-A, will help to plan methods for estimation of cost-effectiveness in the future trial.Means, standard deviations, and the correlation between baseline and follow-up scores on continuous outcomes will be reported to inform the sample size calculation for the subsequent definitive trial.Level of clustering within groups in the intervention arm will be quantified using the intra-cluster (intra-group) correlation coefficient to inform the sample size calculation for the definitive trial; however, we recognise the relatively small sample size for this purpose, and it will be used alongside information about levels of clustering in published studies of trials of similar group-based interventions in similar settings.p values, in line with the extension to the CONSORT statement for reporting randomised pilot and feasibility studies [We will compare the outcomes at follow-up between the two trial arms based on the intention-to-treat principle with participants analysed according to the trial arm they were randomised to. Missing data will not be imputed. We will report only confidence intervals for the intervention effect and no  studies .Descriptive statistics will be reported for the quantitative data collected in delivery observation checklists, facilitator checklists, checklists used to assess intervention session recordings, and participant feedback forms.Qualitative data collected from feedback forms, interviews, and focus groups will be analysed thematically to provide insights into participants’ experiences of the programme, intervention acceptability, and suggestions for improvement, and to enhance understanding of the impact of the intervention and the mechanisms of change in relation to the programme logic model . Data wiNVivo software  will be used to organise and analyse the qualitative data. Initially, two researchers will independently read and code line-by-line a sample of the data and discuss their coding to develop and agree on the coding framework. New codes may be added as the coding proceeds, and the codes and coded data will be reviewed. Codes will be defined, compared to each other, and organised into categories and themes. Attention will be paid to negative, or ‘deviant’, cases to inform developing themes and interpretation. Short summaries of each interview will be also written to explore how individual experiences and views of the intervention may differ between participants. The analysis and interpretation of the data will be regularly discussed with the research team. A detailed record will be kept of the analysis process, including definitions of the themes and concepts and their application.Recruit a minimum of 48 participants, which is the minimum number that will enable all six sites to be randomised and the intervention to be testedDeliver 6 groups in total for the intervention arm, assessed by establishing 6 venues, and identifying and training facilitators, and groups completing the programme curriculumAt least 80% of participants completing measures at 6-month follow-up or a clear plan to achieve this in the trialWe will interpret the findings of this feasibility trial and report the implications for progression to a definitive randomised controlled trial of the HPC programme. This will include any necessary amendments to the intervention content and delivery, as well as the development of a train-the-trainer manual to be used in training future facilitators of the programme. The following indicators of feasibility will be used to determine whether a definitive randomised controlled trial is feasible with the current trial design and procedures:If any of these indicators are not met, the research team will consider whether a definitive trial may not be feasible or whether changes to the design or procedures and further feasibility testing are needed. The need to translate programme materials into other languages will also be taken into account for a subsequent trial.A complete and transparent report of the trial will be produced with reference to recommendations of the CONSORT 2010 statement: extension to randomised pilot and feasibility trials, including a CONSORT participant flow chart . The repNHS England’s Commitment to Carers states ‘Helping carers to provide better care and to stay well themselves will contribute to better lives for those needing care and more effective use of NHS resources’ . HoweverThe main milestones are as follows. Ethical approval for the study was received on 20 August 2018. The trial was registered on 25 October 2018 (ISRCTN 15144652). Recruitment of participants began on 29 October 2018. The analysis of data on fidelity and process evaluation will be conducted following data collection (summer to autumn 2019). The analyses of outcome measures will be conducted in February 2020. The expected date of completion is June 2020.Additional file 1. SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents*.


Data phenotyping traits on soybean seeds such as shape and color has been obscure because it is difficult to define them clearly. Further, it takes too much time and effort to have sufficient number of samplings especially length and width. These difficulties prevented seed morphology to be incorporated into efficient breeding program. Here, we propose methods for an image acquisition, a data processing, and analysis for the morphology and color of soybean seeds by high-throughput method using images analysis. As results, quantitative values for colors and various types of morphological traits could be screened to create a standard for subsequent evaluation of the genotype. Phenotyping method in the current study could define the morphology and color of soybean seeds in highly accurate and reliable manner. Further, this method enables the measurement and analysis of large amounts of plant seed phenotype data in a short time, which was not possible before. Fast and precise phenotype data obtained here may facilitate Genome Wide Association Study for the gene function analysis as well as for development of the elite varieties having desirable seed traits. Accurate measurement and definition on morphology and color measurements of seeds are very difficult to obtain because it is time consuming and requires effort even for small number of samples. Most importantly, it is almost impossible to have objective data sets for colors and shapes of seeds with conventional methods. To overcome these issues, recent plant-phenotypic studies using images have been conducted ,4,5,6,7.The phenotypic analysis of soybean seeds was carried out using optical properties. One hundred soybean seeds were photographed at one time using a digital camera and the morphological and color indexes of each soybean seed were calculated through image processing. We also analyzed the characteristics of the data values on the measured results using the images. We devised a method for analyzing high-throughput method soybean seed phenotype using images to measure the phenotype of 39,065 seeds. And, we designed a phenotype analysis flow-chart as shown in First, the data creation of the red block A in Data processing of images taken using ImageJ program was performed. The data processing of the green block B in We integrated the data measured in the image processing stage using python programming and analyzed the morphology and color relation as shown in orange box C in It is too much time and effort for each individual to analyze 39,065 phenotypic analyzes of soybean seeds. Therefore, we took 100 seeds in one line in the data creation and processed the process and analysis through macro and programming like the gray block D in We measured 8 kinds of morphological data such as area, perimeter, width, height, thickness, circularity, roundness, and solidity  12] in  in 12] iThe eight morphological phenotype data thus measured can be used to compare and analyze agricultural traits between lines . It can Pentatomidae and detected three D, E, F seeds with solidity values of less than 0.97. According to the results, it was possible to detect seeds showing a specific morphology.In addition, using solidity values representing the smoothness of the surface, we also detected soybean seeds with specific morphology as shown in Information on the color of soybean seed is very important because it relates to various traits such as functional substances, diseases, and the environment ,15,16. TWe used python program to analyze of all soybean seeds in the same method as in The ability to be able to deal with large same kinds and numbers in an accurate manner are crucial to increase the discrimination power of an identification system because they depend not only on the intra-specific representativeness of the analyzed samples but also on the quality and quantity of the parameters measured and used to discriminate among groups, as well as on the dimension and variability degree of the groups according to recent papers ,19. EvenHere, we used Analyze particles function of ImageJ  to extraIn the current paper, we present a method of precisely investigating individual phenotypic information on various types of morphology and color in soybean seeds using high-throughput and an analysis method as the purpose of this study. As results, this method enables the investigation of large numbers of samples that are difficult for humans to measure and analyze the phenotypic data of plants that are time-consuming and labor intensive. We could rapidly measure and analyze about 39,065 soybean seeds of 400 lines in the proposed method. There have been no studies to deal with such number for seed phenotyping in this much accuracy. Furthermore, we opened new window for the seed color data collection which was very difficult to measure in an objective manner. These results could be applied to various analysis for shapes which are well addressed by Bianco et al.  and Cerv