Halkida, Greece

The Norwegian Immunotherapy in Multiple Myeloma Study

Guided Internet-Based Treatment for Harmful Alcohol Use; EBehandling Alkohol

Introduction Harmful alcohol use is a pressing issue that affects individuals, families, and society as a whole, posing a significant public health problem. For the individual, harmful alcohol use can lead to mental and physical health issues, as well as social and relational problems. From a societal perspective, it can result in reduced work capacity, increased sickness absence, crime, violence, accidents, and injuries. In Norway, at least 17% of the adult population engages in potentially harmful alcohol consumption. This leads to many inpatient stays in both somatic and psychiatric hospitals. Reducing high alcohol consumption can yield substantial health benefits and significant societal savings. The public health services for alcohol use disorder in Norway fall within the interdisciplinary specialized addiction treatment (Tverrfaglig Spesialisert Rusbehandling; TSB). TSB offers various treatment options, predominantly outpatient treatments through individual or group therapy sessions. An ongoing study at Vestfold Hospital Trust, titled "Patient factors predicting completion and outcome in group treatment of alcohol use disorders" (the "Predictor study"), explores how patient factors (psychological, sociodemographic, and societal) predict outcomes in group treatment for alcohol use disorders (AUD). This study tracks participants through approximately 3 months of treatment and follows up at 1 and 3 years post-treatment. Despite available treatments, a significant proportion of people with emerging alcohol problems do not seek help early on, missing the opportunity for early intervention. The reasons for this reluctance are varied and complex. Feelings of shame and guilt over having an emerging alcohol problem can prevent some individuals from seeking health care. Additionally, treatment may be inaccessible, or the available treatment options may not be tailored to the individual's needs. Common barriers include the necessity for GP referrals for TSB treatments, the prioritization of treatment for severe cases of alcohol use, financial constraints, and the logistical challenges of traveling to outpatient clinics while balancing studies, work, or family responsibilities. Needs Description eBA (eBehandling Alkohol) is a guided internet-based treatment for problematic alcohol use, developed through a collaboration between Vestfold Hospital Trust and Haukeland University Hospital. The treatment is grounded in cognitive behavioral therapy (CBT) and motivational interviewing (MI). It provides patients with access to self-help modules containing information, questionnaires, and tools useful for the process of reducing alcohol use. Patients regularly complete questionnaires that measure changes in alcohol use, other drug use, physical and mental health, and quality of life. These questionnaires are integrated into the treatment program and help therapists monitor and adjust the treatment. Patients can use their questionnaire results to assess whether the treatment is helping them achieve their goals. In the planned research project, data from these questionnaires will be utilized to answer the research questions. Patients are guided by therapists through written messages in the treatment program or by telephone. One of the main advantages of eBA is the potential to offer treatment for harmful alcohol use at an early stage, thus preventing further deterioration of the problem. This is invaluable for individuals, their families, and society. eBA is easily accessible, discrete, and can lower the threshold for seeking help by reducing stigma, financial barriers, and logistical difficulties. Evidence from a pilot study using participant data from eBA showed promising results. The participants had a mean age of 49 years, with 60% being men, 65% having a partner, and 76% having children. Approximately 75% of the participants reported a reduction in alcohol use, and reported reduced symptoms of anxiety and depression. These results align with international research that supports guided internet-based treatment for emerging alcohol problems as an effective means of reducing alcohol use and improving mental health. Other studies have shown similar treatments to be helpful for a range of addiction-related problems. However, despite this research, internet-based treatment for alcohol misuse has not yet been broadly implemented in health services. Project Methodology The proposed study will be a prospective multicentre cohort study, following individuals with harmful alcohol use from the initial screening interview, through the start of treatment, during the 9 treatment modules, and at follow-ups at 1 month, 6 months, and 2 years after treatment completion. The target group for this project comprises adult men and women with problematic alcohol use who, for various reasons, do not seek help through traditional treatment options. These individuals must be willing to make an effort to reduce their alcohol use and be eligible to use guided internet-based treatment. Participants must have access to a computer, tablet, or smartphone and be able to securely access the internet-based treatment using BankID. Recruitment will be conducted through press releases, social media, and leaflets distributed at outpatient clinics and GP offices. Interested individuals can inquire about participation by sending an SMS. A therapist will then contact the participants for an initial interview. Inclusion in the study will be based on written informed consent and meeting the inclusion criteria. The questionnaires used in this study are mainly equivalent to those implemented in other guided internet-based treatment programs in Norway, allowing for comparative analysis. Post-treatment efficacy will be assessed at 1 month, 6 months, and 2 years post-treatment. The questionnaires will cover various domains, including demographics, age, sex, education, occupation, main source of income, marital status, children, duration of the problem, previous treatment experience, patient goals, planned alcohol use, drinking patterns, daily alcohol consumption, AUDIT (Alcohol Use Disorder Scale), DUDIT (Drug User Disorder Scale), PHQ-9 (Patient Health Questionnaire), GAD-7 (Generalized Anxiety Disorder), 5Q-5D-5L + VAS (quality of life and treatment satisfaction), DTCQ (Drug Taking Confidence Questionnaire), SCL-10R (Symptom Check List), C-scale (User satisfaction), WHO-1 quality of life, and evaluation & goal achievement. Participants will also consent to the collection of registry data for 1 year prior to treatment start and 2 years after treatment completion. Information about the type and amount of treatment received from specialized and municipal health services will be collected through databases from the Norwegian Patient Registry, the Control and Payment of Health Refunds Registry, and causes of death from the Cause of Death Registry. Qualitative interviews will be conducted through individual semi-structured interviews with approximately 20 participants who specifically consent to this interview. The Predictor study and the Endre study are collecting data that overlap with the eBA study in several areas, providing a basis for conducting meta-analyses. Data compared from the three studies will be anonymized and aggregated at the group level. The pilot study indicated an average decrease in AUDIT score from pre-treatment to module 8 (T2) of 3.45, with a standard deviation of 4.76. With a sample size of 250 individuals, the width of a 95% confidence interval is estimated at 1.23, with a probability of 0.8 of achieving the estimated width. This interval width increases to 1.55 if the final sample size at module 8 is reduced to 160 individuals due to a 36% dropout. Adjusting for additional factors in the statistical analysis requires an increase in sample size. Given these precision estimates, accounting for potential dropouts, and the need to adjust for additional factors, a sample size of 250 individuals is satisfactory. Treatment outcome/retention in treatment will be analyzed using survival analyses such as Kaplan-Meier/Cox regression. Outcome measures will undergo regression analyses on short-term (T2) and long-term (T4 and T5) outcomes, with primary measures being alcohol use, physical and mental health symptoms, and quality of life. Descriptive data will be provided as mean and/or median values, along with standard deviations and/or 95% confidence intervals. The significance level/p value is set to < 0.05. Meta-analyses will be conducted using data from the eBA study, the Predictor study, and the Endre study. Participants, Organization, and Collaborations The eBA program and the associated study will be managed and organized from Vestfold Hospital Trust. The Division of Mental Health and Addiction was responsible for developing eBA as an experimental treatment program and for conducting the pilot study. This division has expertise at all levels of implementing and conducting guided internet-treatment programs. Several hospitals will participate in eBA implementation: Sørlandet Hospital Trust, Akershus University Hospital, Innlandet Hospital Trust, St. Olavs Hospital, and Vestfold Hospital Trust. Written agreements will ensure cooperation among these hospitals. A project group will be established to coordinate the daily operations of the treatment program. This group will comprise local representatives from Vestfold Hospital Trust and coordinators at the collaborating institutions. Designated clinicians at participating hospitals will receive training and supervision from experienced clinicians at Vestfold Hospital Trust. A steering committee for the research project will include representatives from the participating hospitals and the Predictor and Endre studies, as well as a user representative. The Research Group for Substance Use and Addiction at Vestfold Hospital Trust will serve as the reference group for the research project.For research independence, researchers and the PhD candidate will not perform tasks involving therapeutic guidance of participants. Plan for Implementation eBA, trialed as an experimental treatment at Vestfold Hospital Trust, will be implemented as a treatment option in selected hospitals in 2024. The questionnaires integrated into the eBA program assessing alcohol use, somatic, and mental health will enable seamless data collection for the research project. The study's results will inform whether eBA can become a standard treatment option for people with harmful alcohol use. The goal is to demonstrate positive outcomes and satisfaction, highlighting eBA's accessibility, potential to increase treatment numbers, and cost-effectiveness. Findings will be shared with health authorities and published in high-ranking international peer-reviewed journals. Given its close link to clinical practice, the research results will be readily relevant for clinicians. The implementation of eBA is expected to utilize existing resources within Norway's substance use disorder treatment infrastructure. Clinicians are familiar with this patient group and their follow-up needs. A meta-analysis comparing results from eBA, the Predictor study, and the Endre study is anticipated to clarify which individuals benefit most from different treatment options. Offering varied treatments tailored to each individual's stage of problem development is crucial for providing comprehensive care. User Involvement The Addiction Research Group at Vestfold Hospital Trust, including a user representative, will act as the project's reference group. The user representative has been involved in drafting the project outline and research questions and will continue to advise on and participate in the study throughout its duration. Ethical Considerations Adhering to the Helsinki Declaration's principles and other applicable regulatory requirements, the study will maintain high ethical standards. Participants' data will be registered per national personal data laws, with approval from regional ethical committees and Data Protection Officers at each participating hospital. To safeguard research independence, the researchers or PhD candidate will not conduct tasks involving therapeutic guidance of participants. Participants will provide written consent before inclusion and can withdraw at any time. Recruitment will include both genders, and any significant gender-focused findings will be reported. The study does not involve environmental concerns. Clinicians will monitor participants throughout the project and refer them to traditional treatments if needed. By thoroughly documenting the structured assessment, implementation, and potential broader adoption of eBA, this detailed project framework aims to reduce harmful alcohol use through innovative internet-based treatments. These treatments are anticipated to be effective, accessible, and broadly beneficial, offering significant improvements in public health outcomes.

Optimizing Treatment for Patients with Juvenile Idiopathic Arthritis in Sustained Remission: the MOVE-JIA Trial

Effect of Proactive Therapeutic Drug Monitoring on Maintenance of Sustained Disease Control in Adults With Rheumatoid Arthritis on a Subcutaneous TNF Inhibitor: The Rheumatoid Arthritis Therapeutic DRUg Monitoring Trial (RA-DRUM)

There is a considerable variation in serum drug levels among rheumatoid arthritis (RA) patients on tumor necrosis factor inhibitors (TNFi), and a high number develop neutralizing anti-drug antibodies (ADAb). Sub-therapeutic drug levels and ADAb formation are major contributors to TNFi treatment failure and disease flare. Proactive therapeutic drug monitoring (TDM), i.e., individualized drug dosing based on regular assessments of serum drug levels and ADAb, has the potential to optimize the efficacy and safety of TNFi treatment. The aim of the RA-DRUM trial is to assess whether TDM is superior to standard of care in order to maintain sustained disease control without flares in patients with RA treated with the SC TNFi adalimumab. Participants will be randomized to: - Administration of TNFi based on proactive TDM (TDM group) - Administration of TNFi based on standard of care without knowledge of serum drug levels or ADAb status (Standard of care group) Participants will be followed for 18 months with on-site visits at baseline, 4, 8, 12 and 18 months and digital visits at 2, 6, 10, 14, and 16 months. Blood sampling for serum drug levels and anti-drug antibodies will be done at all visits.

Study of Navtemadlin as Maintenance Therapy in TP53WT Advanced or Recurrent Endometrial Cancer

Study of Perioperative Dostarlimab in Participants With Untreated T4N0 or Stage III dMMR/MSI-H Resectable Colon Cancer

The Norwegian World Health Organisation Labour Care Guide Trial (NORWEL)

A large robust trial investigating the effect of the LCG is needed to establish a foundation of knowledge on which the decision of implementing the LCG on a national level should be based. The Norwegian WHO LCG trial addresses the WHO research priority question: "What is the effect of the LCG on processes of care, health, well-being and outcomes during labour and childbirth?". The trial will have a special focus on intrapartum caesarean section rates and experience of labour. The overall aim of the trial is to test the LCG in an unbiased population in a Norwegian setting. The project will conduct a nationwide randomized controlled trial (RCT) to test the effect on labour interventions and maternal and neonatal outcomes compared to the previous WHO partograph. The Norwegian WHO LCG trial will be conducted through three work packages: WP1 consists of a feasibility study to develop an electronic version of the LCG, and will test its validity and usability prior to the planned RCT. WP2 consists of a stepped wedge RCT to assess the effect of the LCG on labour interventions and maternal and neonatal outcomes. WP3 consists of a survey to investigate patient reported outcome through the childbirth experience questionnaire (CEQ). This is a stepped wedge multicenter cluster randomised non-inferiority trial, to be conducted within the nationwide NORBIRTH network for clinical obstetric research. The hospitals will act as clusters and the women as individual participants. During the trial period all hospitals will use the WHO partograph and the LCG according to the trial protocol for all women with a planned vaginal delivery, these women constitute the trial population. Women who want to opt out will not be included in the analyses. Each hospital has established local research groups which are dedicated to implement the project. The included hospitals will consent to adhere to the protocol in the trial period and state that they have the capacity to participate both logistically and practically. Local coordinators will be appointed with the responsibility of monitoring the trial and secure a thorough documentation according to the protocol.

DESTINY Breast Respond HER2-low Europe

This non-interventional study will investigate the effectiveness withT-DXd, the demographic and clinical characteristics of the patients, treatment patterns, tolerability, management of adverse drug reactions (ADRs), and patient experience of T-DXd in patients with HER2-low unresectable and/or metastatic breast cancer. Patients will be treated according to the proposed indication statement in the Summary of Product Characteristics (SmPC). No drug product will be administered as part of this study. Data on conventional chemotherapy (i.e., including but not limited to capecitabine, eribulin, gemcitabine, paclitaxel and nab-paclitaxel) will also be collected in a disease registry part of the study.

The Mother in Norway Study

The Norwegian government has since 2015 been in the process of implementing the Nurse Family Partnership program (NFP) in Norway, as a possibly important part in their strategy to combat child abuse and social inequality. This study employs an individually randomized controlled parallel-group trial where participants are randomly assigned to experimental and control groups. The planned study population is 700 mothers total (350 in the treatment group and 350 in the control group) to be enrolled over 2 years (June 2023 -2025), with NFP services delivered to the treatment group through the children's second birthday (2025-2028). The control group will receive the standard of care and whatever other programs and services are available in the community. Primary outcome is violence towards first-time mothers and their children. In their last trimester, and when the child is 6, 12 and 24 months old, mothers included in the study will receive a questionnaire assessing perceived partner violence, parenting skills, coping, control, and the child's development and language. At 24 months, staff at health stations will perform the Bayley observation test of the child´s development and language. The study will also utilise administrative data to assess the effects of NFP on a wide range of health- and health related outcomes. All analyses are carried out blinded. The investigators estimate "intention-to-treat" (ITT) effects and per-protocol analysis. Cost-effectiveness analyses will be conducted to compare the value of NFP to existing services, and to improve the efficiency in the delivery of NFP.

Advanced Care Planning for the Severely Ill Home-dwelling Elderly

Background: Severely ill elderly patients and their relatives are often poorly involved in treatment and care decisions. Advance care planning is a well-documented tool to comply with the ethical and legal imperative to involve both the patient and their next of kin in the planning of current and future treatment and care. The overall aim of this project is to improve health services, user involvement and quality of life for severely ill elderly people living at home, and their relatives, in an efficient, sustainable and coordinated way, through better implementation of Advance care planning (ACP). Setting: Twelve hospital wards providing care to acutely admitted elderly home-dwelling patients, either pure geriatric units or mixed units with specialists in geriatric medicine. Research questions: 1. What is the current level of implementation of ACP for home-dwelling elderly patients with severe somatic disease in the participating clinical units? 2. What are the most important facilitators and barriers among all relevant stakeholders - to implementing ACP at the a) clinical, b) health care service- and c) national, regional and municipal level? 3. What are the most important moral dilemmas and conflicting interests related to ACP, and how can these be resolved? 4. What are the benefits and disadvantages with the implementation support and ACP experienced by the patients, among next of kin, health personnel and implementation teams? 5. Does the implementation support program - compared to no such support - improve a) the implementation of ACP (fidelity), b) quality of communication and decision-making for patients and relatives when approaching the end of life, and c) congruence between the patient's preferences for information and involvement and the attending clinician's perceptions of the same, and other relevant outcomes for patients, relatives, and the attending clinicians? 6. Is the implementation support program associated with changes in health personnel's perceptions, attitudes, self-efficacy, confidence in, and experiences in relation to information giving and involvement of patients and relatives? 7. Is higher level of implementation (fidelity) of ACP associated with improved outcomes for patients, relatives, the staff and the services? 8. Is the implementation support program for ACP a cost-effective intervention? Hypotheses: 1. The current level of implementation of ACP for home-dwelling elderly patients with severe somatic disease in participating clinical units is low. 2. There are important facilitators for and barriers to implementing ACP among all stakeholders at the a) clinical, b) health care service- and c) national and other higher levels. 3. There are important moral dilemmas and conflicting interests related to ACP, and they can be dealt with through systematic approaches and ethics reflection. 4. Patients, among next of kin, health personnel and implementation teams experience both benefits and disadvantages with the implementation support and ACP. 5. The implementation support program - compared to no such support - will improve a) improve the implementation of ACP (fidelity), b) quality of communication and decision-making for patients and relatives when approaching the end of life, and c) congruence between the patient's preferences for information and involvement and the attending clinician's perceptions of the same, and other relevant outcomes for patients, relatives, and the attending clinicians. 6. The implementation support program is associated with changes in health personnel's perceptions, attitudes, self-efficacy, confidence in, and experiences in relation to information giving and involvement of patients and relatives 7. Higher level of implementation (fidelity) of ACP is associated with improved outcomes for patients, relatives, the staff and the services 8. Outcomes for patients, relatives and the public health- and welfare services justify the costs of the implementation support program and of ACP in routine care.