Investigator Initiated Research Opportunities | Takeda Pharmaceuticals

Maribavir - US Only

• Studies exploring maribavir effectiveness and safety in the real-world setting including:

  • Immunocompromised patients with high-risk of Cytomegalovirus (CMV) infection

  • Recurrent CMV

  • Longer term impact, early treatment (e.g., preemptive, 1st line therapy/treatment)

  • Diverse demographic populations (e.g., racial, ethnic)

  • Patterns of use

• Studies focusing on effectiveness of maribavir following letermovir use or combination therapy

• Studies examining the impact of maribavir on Health Related Quality of Life Measures (HRQoL) and Patient Reported Outcomes (PROs) among thoracic (heart/lung) transplant patients with CMV infection

Maribavir – outside US

• Real-world studies further exploring the role of maribavir in CMV management, including:

  • a) In post-transplant sub-populations with high unmet needs related to CMV infection, including those intolerant or at risk of intolerance (e.g., those with myelosuppression/immuno-dysfunction and/or renal dysfunction) to other anti-CMV antivirals

  • b) Assessment of earlier treatment initiation (e.g., impact of earlier switching to secondline treatment)

  • c) Patterns of use, including exploring the eƯects of treatment duration on patient responses and outcomes

Lanadelumab

• Real-world clinical effectiveness and safety of lanadelumab in patients, including those who have previous experience with alternative therapies for HAE (including pediatrics and other special populations)

• Composite effectiveness end-points (e.g. patient-reported outcomes and attack-free status) in patients with HAE treated with lanadelumab (including pediatrics and other special populations)

HAE

• Approaches to facilitating diagnosis and decreasing diagnostic delay

• The burden of illness and burden of treatment, including pediatrics, other special populations, and patients with sub-optimal outcomes

• Explore/define the epidemiology of HAE (adults and pediatric population)

Ulcerative Colitis (UC), Crohn’s Disease (CD) and Inflammatory Bowel Diseases (IBD)

• Understanding the biological mechanisms that drive clinical response to vedolizumab in TNF-naïve/other biologics versus exposed patients with UC/CD

• Characteristics (including biomarkers) of optimal vedolizumab patients

• Prognostic biomarkers for responders/non-responders of vedolizumab

• Transmural healing with vedolizumab

• Efficacy of vedolizumab on novel PROs (e.g. bowel urgency)

• Efficacy and safety of vedolizumab in combination with advanced/conventional therapeutic agents in UC and CD

• Understanding biological mechanisms (including omics/histology) of combining different MoAs

• Disease modification by vedolizumab in CD and UC

• Real-world disease clearance by vedolizumab in UC

• Real-world SC vedolizumab efficacy and safety

• Data on SC vedolizumab (e.g. switching patterns from SC to IV and vice versa, different SC dosing regimens)

• Data on Diversity, Equity and Inclusion in patients with IBD

Gastrointestinal Fistulizing Conditions

Clinical outcomes

• Effect of long-term seton versus short-term seton on subsequent fistula treatment success

• Mechanistic effects of Allogeneic mesenchymal adult stem cells (aMSC) in fistulizing conditions

• Dissemination of existing data/education supporting allogeneic stem cells (pros and cons of autologous and allogeneic)

• Effect of multidisciplinary teams and/or patient involvement in shared decision-making on fistula outcomes

• Fistula surgeries: post-surgical complications and/or short-term health-related quality of life (HRQoL) and work productivity

• Impact of radiological fistula healing on fistula recurrence

• Histological, molecular or radiological characterization of cell-mediated perianal fistula healing

• Identification of optimal treatment targets in gastrointestinal fistulizing conditions leading to long-term remission

Translational research

• Identification, development, and characterization of pre-clinical in vivo proof of concept and in vitro cellular models predictive of fistulizing pathobiology

• Microbiome composition in fistulizing conditions such as Complex Perianal Fistula (CPF) (fistula swabs, stool samples)

• Cellular composition and characterization of inflammation in Crohn’s disease complex perianal fistula and/or complex cryptoglandular fistula

Celiac Disease (CeD)

• Adoption of new methods and technologies to diagnose and manage patients with celiac disease:

  • use of video capsule endoscopy (VCE) tools for diagnosing and monitoring CeD and its role in clinical guidelines

  • tools and studies objectively assessing real world gluten exposure

• Gluten exposure/challenge design in clinical trials

• Biomarkers of the future when monitoring CeD

• Disease burden in special populations with highest unmet need (pediatric, adolescents, elderly)

• Correlation of histology/serology/symptoms/other risk factors with disease progression/complications

• Epidemiology studies

• Humanistic burden and patient / healthcare professional (HCP) preferences

• Disease pathophysiology (especially advances in immunology)

• Optimization of gluten-free diet (GFD) when managing CeD

• New modalities and development targets in CeD

• New indications with relevance to gluten sensitivities/wheat allergy

Prucalopride - US Only

• Pilot studies in Functional Gastrointestinal Diseases with rationale for prokinetic use

• Safety and efficacy of prucalopride in secondary causes of constipation

• Real world, retrospective studies of prucalopride in adults with chronic idiopathic constipation

Alpha-1 Antitrypsin Deficiency (AATD) Liver Disease

• Studies focusing on identification and validation of non-invasive methods for assessment of liver fibrosis in AATD

• Studies exploring predictors of disease progression in AATD liver disease or for the development and or progression of liver disease in patients with or without AATD lung disease

• Studies exploring novel markers for the early identification of patients with AATD-LD and diagnostic characterization of disease stage

• Studies evaluating correlations between intrahepatic globule accumulation, patient-centered outcomes and/or clinical outcomes

Eosinophilic Esophagitis (EoE) – US Only

• Identification of non-invasive, or minimally invasive diagnostic and monitoring techniques in EoE
• Development and validation of symptom monitoring tools implementable for patient care
• Impact of disease severity on EoE treatment outcomes
• Development of tools (questionnaires, artificial intelligence tools, etc.) to improve EoE patient identification across the multidisciplinary team
• Further understanding into ways to improve diagnosis rates and engagement with healthcare in under-represented populations within the EoE community
• Real-world evidence of safety and efficacy with budesonide oral suspension
• Predictors of response to EoE therapy, with special focus on predictors of response to budesonide oral suspension

Dravet syndrome or Lennox-Gastaut syndrome

• Disease management, treatment patterns, rational polytherapy, predictors of treatment response or discontinuation, Health Resources Utilization (HRU), or long-term treatment outcomes

• Novel tools for diagnostics

• Novel technological approaches for assessing seizure burden (including wearable EEG device monitor, AI, NLP or ML)

• Novel composite outcomes that incorporate both efficacy (such as seizure symptoms, non-seizure symptoms, patient sub-groups, seizure duration, etc.) and safety-related concepts

• Linkage of genotype to clinical phenotype and/or treatment response

• Burden of illness, caregiver burden and/or treatment pattern burden

• Understand the patients’ or caregivers’ perspective in measuring the importance of components for Quality of Life

• Understanding and quantifying residual seizure burden

Narcolepsy and Idiopathic Hypersomnia

• Explore the role of orexin in the pathophysiology of narcolepsy and idiopathic hypersomnia

• Functional outcomes research related to treatment patterns for narcolepsy and idiopathic hypersomnia

• Characterize the disease burden and unmet needs of patients with narcolepsy and idiopathic hypersomnia

Hemophilia A

• Studies examining the cost efficiency of recombinant Antihemophilic Factor (ADVATE) and PEGylated –recombinant Antihemophilic Factor (ADYNOVATE/ADYNOVI) with or without myPKFiT

• Studies examining the relationship between FVIII levels and the occurrence of bleeds at varying physical activity levels with or without the use of the myPKFiT mobile app

• Studies to investigate changes in adherence and quality of life (QoL) in patients using recombinant Antihemophilic Factor (ADVATE) and the myPKFiT patient app

• Real World Evidence on use of PEGylated -recombinant Antihemophilic Factor (ADYNOVATE/ADYNOVI), an extended half-life rFVIII (EHL rFVIII), in clinical practice with or without myPKFiT (including safety, efficacy, utilization, QoL, adherence, patient satisfaction etc.)

• Studies on other non-coagulation effects of Factor VIII

• Studies looking at the GOAL-HEM (Goal Attainment Scaling for Life – Hemophilia) as a patient-centered reported outcome measure to monitor clinical progress

• Non-clinical studies on Polyethylenglycol (PEG) safety

• Role of PEGylated -recombinant Antihemophilic Factor (ADYNOVATE/ADYNOVI) for tolerization or in previously tolerized/partially tolerized patients

• Studies to investigate appropriate assessment of joint health and prevention/management of all bleeds including subclinical

• Studies to investigate benefit of FVIII replacement therapy vs. non-factor therapy in optimising bleed outcomes

Recombinant-porcine Antihemophilic Factor and Acquired Hemophilia (AHA)

• Prospective or retrospective studies that provide insights on first-line use, loading dose, dosing over time, FVIII:c and anti-drug antibodies

• Explore efficacy and safety of recombinant-porcine Antihemophilic Factor in patient subpopulations (i.e. post-partum or patients with specific comorbidities) with AHA

• Relationship between treatment effectiveness, FVIII level and anti-pFVIII inhibitor titer in subjects with AHA receiving recombinant-porcine Antihemophilic factor

• Development/validation of dosing algorithms for recombinant-porcine Antihemophilic factor, initial and follow-on, when the anti-porcine FVIII titers are unknown.

• Relationship between treatment effectiveness and recombinant-porcine Antihemophilic factor dosing in subjects with AHA

• Explore the potential use of recombinant-porcine Antihemophilic factor as treatment for breakthrough bleeds in patients treated with non-factor therapies [i.e. Emicizumab]

• Studies intended to develop flexible and tailored dosing regimens for recombinant-porcine Antihemophilic Factor

• Investigate effectiveness, safety and treatment outcomes of the continuous infusion of recombinant-porcine Antihemophilic Factor

• Collect long term data on treatment for patients with AHA

• Clinical outcomes of Anti-Inhibitor Coagulant Complex for treatment of AHA patients

Hemophilia Gene Therapy

• Measures to evaluate outcomes with hemophilia gene therapy (clinical, humanistic, quality of life, economic, biomarkers, etc.)

Thrombotic Thrombocytopenic Purpura (TTP)

• Long-term outcomes, disease progression and treatment burden associated with plasma-based therapy; outcomes associated with rADAMTS13 treatment

• Epidemiology, disease burden, health care utilization and quality of life of TTP patients

• Risks for poor outcomes associated with functional ADAMTS13 deficiency; genotype/phenotype correlations among patients

• The relationship between subacute manifestations and development of disease-related complications; using clinical biomarkers as indicators of disease-related complications; diagnostics

von Willebrand Disease (VWD)

• Projects aiming to improve knowledge in the management of prophylaxis, heavy menstrual bleeding (HMB), post-partum bleeding, gastrointestinal (GI) bleeding, severe epistaxis, major surgeries

• Comparison of plasma-derived von Willebrand factor (pdVWF) and recombinant von Willebrand factor (rVWF) in the treatment of GI bleeds or HMB

• Effectiveness and safety of von Willebrand factor (VWF) in on demand/surgery and prophylaxis in real world setting (including elderly patient or those having a cancer or thrombotic risk)

• Personalization of VWD therapy (genetic, bleed prediction, bleeding assessment tools, multidisciplinary approach, …)

• Studies to examine the relationship(s) between the rVWF characteristics, its half-life, its multimeric profile and its clinical efficacy

• Role of VWF multimeric forms in the control of angiogenesis including biomarkers of angiogenesis (rVWF in angiodysplasia)

• Impact of long-term management of joint bleeds on quality of life (QoL) and/or healthcare resource utilization (HRU); impact of the management of HMB on QoL and HRU

• Assessment of the efficacy of VWF (pdVWF or rVWF) in acquired VWS – left ventricular assist device (LVAD), extracorporeal membrane oxygenation (ECMO)

Adrenal Insufficiency

We are not accepting new IIRs for this area

Hypoparathyroidism

• Hypothesis generating studies on the beneficial effects of Natpar/a on short-term symptomatology and quality of life and long -term function of organs/systems (i.e., Brain, CVD, Renal, Bone, Glucose metabolism, immune function) in chronic HypoPT patients not ade - quately controlled with conventional therapy

• Physiology of interaction between PTH N-terminal and C-terminal with the PTH Receptors PTHR1 and PTHR2, circadian rhythm & clinical implications

• In-vivo and in-vitro mechanism of action (MOA) including non-clinical studies

Hunter Syndrome

• Analyses of natural history of MPSII

• Studies involved in the development or evaluation of biomarkers or diagnostic capabilities in MPS II

• Studies examining:

  • Impact of early diagnosis, including screening, and treatment start

  • Long term treatment effectiveness of Idursulfase (also retrospective)

  • Early diagnosis of cognitive impairment

  • Neurodevelopmental assessment

  • Standardization of cognitive testing

  • Neuronopathic MPS II Disease course

• Studies of genotypes and phenotypes, as well as their correlation, in different geographies

Fabry Disease

• Studies for the development or evaluation of biomarkers or diagnostic capabilities to:

  • Identify high risk populations

  • Facilitate early disease detection

  • Detection of early disease progression

  • Monitor disease progression

  • Predict/measure therapy effectiveness

• Research on cardiac treatment outcomes

• Studies of genotypes and phenotypes, as well as their correlation, in different geographies

• Studies on disease progression in specific agalsidase alfa treated sub populations or segments (e.g., females and pediatrics subjects).

• Studies on early treatment

• Studies examining outcomes in patients with amenable mutations

• Research fostering understanding of inflammation and immunogenicity in Fabry disease (FD)

Gaucher Disease

• Screening for patients with Gaucher disease

• Generation of data on patient reported outcomes (PRO)

• Generation of data on the role of Lyso-Gb1 as a novel biomarker

• Studies fostering understanding of inflammation and immunogenicity in Gaucher disease

• Enzyme replacement therapy (ERT) infusion optimization (e.g. location (hospital/home), infusion pumps, etc.) that could have potential positive impact on patient experience and patient Quality of Life (QoL)

• Genotypes and phenotypes

Mucopolysaccharidosis Type II (MPS II) / Hunter Syndrome

• Studies examining impact of early diagnosis, including screening, and treatment start

• Exploring the utility of digital technologies for achieving earlier diagnosis

• Areas relating to implementation of newborn screening (NBS) programs e.g. feasibility and pilot studies; follow-up on outcomes in patients identified by NBS programs

• Studies of the long-term effectiveness of Idursulfase

• Studies on the natural history of MPS II

• Studies exploring the development or evaluation of biomarkers or diagnostic capabilities in MPS II

• Support lab and imaging research of disease markers and surrogates predictive of MPS II, including its neuronopathic form.

• Development of novel methods to diagnose neuronopathic MPS II early, including neurocognitive/behavioral assessments

• Studies examining neuronopathic MPS II Disease course

• Improve understanding of genotype phenotype relationship in MPS II

• Novel utilization of Projected Retained Ability Score (PRAS) methodology in research and clinical practice

Chronic inflammatory demyelinating polyneuropathy (CIDP)

• Real world studies on effectiveness and safety of facilitated subcutaneous immunoglobulin 10% (fSCIG 10%) in CIDP maintenance therapy

• Studies looking at fSCIG 10% use and outcomes in CIDP patients switching from prior therapies (including rationale to switch, patient preference and satisfaction)

• Studies exploring use and impact of patient preferred/flexible dosing schedules, accelerated ramp-up/no ramp-up in fSCIG 10%

• Studies addressing humanistic burden of disease in CIDP patients and caregivers

• Research that intends to identify biomarkers for diagnosis or to predict disease progression and treatment outcome

• Studies intended to improve patient care, for example using digital solutions for monitoring CIDP symptoms/disease

Immunodeficiencies

Secondary Immunodeficiency (SID)

• Studies that intend to understand the course of infections in patients with cancer- and treatment-related SID (especially bispecific antibodies treatment, chimeric antigen receptor (CAR) T-cell therapy, post hematopoietic stem cell transplant (HSCT), and solid organ transplantation (SOT)), for example: timing of infections, frequency, type, severity, and impact on patient outcomes and treatment

• Studies that aim to establish or validate existing predictive model or to identify biomarkers that could help to select patients at high risk of developing infections in cancer-related and treatment-related SID

• Studies with a focus on understanding who would benefit the most from prophylactic or on-demand immunoglobulin (IG) therapy

• Analyses that quantify and qualify the impact of SID and/or impact of IG therapy (prophylactic and on-demand) vs standard of care (SOC) on clinical and patient-related outcomes (e.g. efficacy, long term safety, quality of life (QoL), personalized health, perceived health, health care resource utilization (HCRU), and continuity of cancer treatment)

• The impact of IG replacement therapy (IGRT) on cancer outcomes and treatment effects (in addition to its role in SID)

Primary Immunodeficiency (PID)

• Real-world evidence studies that provide insights into usage and administration parameters of subcutaneous immunoglobulin (SCIG) products, particularly in special populations not yet sufficiently studied (e.g. patients who are underweight, patients with certain comorbidities)

• Studies that assess and evaluate quality of life (QoL), personalized health and perceived health for IG replacement therapy

• Studies that explore novel or validate existing approaches in support of earlier PID diagnosis – especially those that could have global impact

• Studies with a focus on understanding the full presentation of PID including the impact of comorbidities on PID and/or vice versa

• Studies that assess and evaluate the application of new device or digital health concepts in the management of PID

Albumin

• Clinical and analytcal studies related to the concept of functional albumin
• Clinical experience with Flexbumin in patients with liver disease, and patients managed in intensive care units (ICUs)
• Central line-associated bloodstream infectons (CLABSIs): Burden of illness, pharmacoeconomic impact and evaluations of preventon strategies
• Clinical outcomes of hyperoncotic (25% albumin) Flexbumin in patients with liver cirrhosis and critical care
• Impact of closed infusion system in albumin therapy on albumin storage, preparation, and handling
• Identification of biomarkers for albumin treatment of consequences or complications of liver diseases and in critically ill patients

Alpha1-antitrypsin (AAT) deficiency (AATD) and AAT Augmentation Therapy:

• AATD pathogenesis, mechanisms, and biomarkers

• AATD clinical, humanistic, and economic burden of illness and co-morbid conditions

• Characterization of MZ patients

• Impact of early diagnosis and screening

• AAT Augmentation Therapy: for example, but not limited to:

  • Adherence in AATD patients with emphysema/chronic obstructive pulmonary disease (COPD)

  • AAT deficient patients in specific populations, (i.e. young adults/adolescents/older/post lung-transplant/forced expiratory volume (FEV) 1 35% Predicted)

  • Exploratory research on anti-inflammatory, immunomodulatory, and tissue protective effects of AAT therapy in non-AATD individuals (i.e. graft vs host disease, autoimmune, rheumatoid arthritis, cardiac)

C1-esterase inhibitor in Hereditary Angioedema (HAE)

• Real-world data (RWD) on effectiveness and safety of on demand use, as well as pre-procedural treatment, short- and long-term prophylaxis with C1-esterase inhibitor in HAE patients
• Understand dosing of C1-esterase inhibitor in the real-world setting
• Switching from oral HAE medications to C1-esterase inhibitor (including, but not limited to, reasons and patients’ perception/preferences/reported outcomes)
• RWD on C1-esterase inhibitor use in special patient populations like children, pregnant or breastfeeding women

For disease related, non-product specific areas of interest please visit Hereditary Angioedema (HAE) section of the website (see above).

Activated prothrombin complex concentrate (aPCC) in Congenital Hemophilia A and B with Inhibitor (CHAWI) or Acquired Hemophilia (AHA)

• Preclinical and clinical studies examining the interaction between co-treatment of aPCC and nonfactor therapies: regimens and doses, clinical outcomes, safety (thrombotic microangiopathy [TMAs] & thromboembolic events [TEEs]), pharmacoeconomic implications, global assays

• Studies examining potential correlations between thrombin generation assay (TGA) parameters and clinical outcomes

• aPCC in the context of orthopedic surgery and rehabilitation

• Clinical outcomes of aPCC treatment in AHA patients

• Outside of CHAWI and AHA, and in populations excluding neonates: Investigate the use of aPCC in clinical scenarios where it is required to reestablish the coagulation cascade (e.g., vitamin K deficiency, reversal of non-vitamin K antagonist oral anticoagulants [DOACs], hepatopathy, etc.)

Prothromplex (4-factor prothrombin complex concentrate)

• Studies assessing patient-related outcomes associated with Prothromplex use
• Studies investigating use of Prothromplex in:
  • patients with acute major bleeds on anticoagulation therapy
  • bleed management (with and without anticoagulant use)
  • patients with factor X (FX) deficiency
  • patients with protein S deficiency
• Studies exploring the use of Prothromplex in post-cardiopulmonary bypass coagulopathy

Severe Congenital Protein C Deficiency (SCPCD):

• Insights into the epidemiology of SCPCD
• Insights into the real-world burden of disease and management of SCPCD
• Clinical significance of plasma protein C levels
• New approaches to SCPCD patient identification and differential diagnosis (e.g., neonatal sepsis)
• Impact of early diagnosis and management of SCPCD
• Efficacy/effectiveness and safety of treating SCPCD with protein C replacement therapy vs other treatment options in acute management as well as in long-term prophylaxis
• Real-world use of protein C replacement therapy in patients (e.g., patients of different ages, different duration of therapy, potential combination use with anticoagulants, etc.)
• Role of protein C in patients with acquired protein C deficiency
• Role of protein C in anticoagulation

Brentuximab vedotin - Outside the US and Canada

• Combination studies in R/R Hodgkin’s Lymphoma with programmed cell death protein 1 (PD-1) / programmed cell death ligand 1 (PD-L1) inhibitors
• Studies which evaluate CD30 expression level, binding and resistance, and reversibility of peripheral neuropathy
• Long term follow-up of BV treated patients (A+AVD/BrECADD) in newly diagnosed HL or in PTCL and CTCL

Contact Pfizer for US or Canadian proposals

Brigatinib - Global

• Studies or Artificial Intelligence (AI)/digital health technologies investigating real-world effectiveness, safety, or optimal sequencing of brigatinib in metastatic ALK+ Non-Small Cell Lung Cancer (NSCLC), as well as patient preferences and quality of life

Cabozantinib – Japan only

• Studies investigating novel treatment therapy after refractory to standard-of-care (SOC) therapy in solid tumors
• Studies exploring predictive factors or investigating novel combination therapies for advanced renal cell carcinoma
• Studies examining actual treatment for hepatocellular carcinoma
• Studies of adverse event management

Contact Exelixis for any proposals outside Japan

Fruquintinib - Global except China, Hong Kong, and Macau

Strong interest:

• Combination studies with fruquintinib in metastatic colorectal cancer (mCRC), utilizing agents with a clear scientific rationale
• Descriptions of the observed effectiveness and tolerability of fruquintinib in mCRC in the clinic population and/or identification of subgroups who may derive the most benefit from the therapy
• Generation of observational data characterizing treatment patterns, safety, and outcomes for patients with refractory mCRC to identify optimal sequencing of agents/mechanisms of action (MOAs)

Moderate Interest:

• Studies exploring fruquintinib as maintenance therapy following chemotherapy in mCRC with/without single agent chemotherapy
• Studies exploring fruquintinib in earlier lines of therapy in mCRC
• Studies exploring fruquintinib in pre-metastatic CRC
• Studies exploring fruquintinib as adjuvant treatment in patients with resected locally advanced CRC and MRD positive disease

Ixazomib - Global

Currently not accepting proposals

Niraparib – Japan, South Korea and Taiwan only*

• Studies on overcoming resistance to PARP inhibitors and platinum-based chemotherapy
• Studies on improving adherence and promoting the appropriate use
• Studies exploring predictive factors or investigating novel combination therapies for ovarian cancer and PARP inhibitors
• Studies investigating novel treatment therapy after refractory to standard-of-care (SOC) therapy in solid tumors

Contact GSK for proposals outside of Japan, South Korea and Taiwan.

Panitumumab – Japan only

Currently not accepting proposals

Contact Amgen for any colorectal cancer proposals outside of Japan

Ponatinib – US Only; Europe, Latin and South America, or Asia Pacific, please reach out to Incyte, Pint, or Otsuka, respectively.

All IIR interest for ponatinib is in Real-World Evidence Studies

Chronis Phase – Chronic Myeloid Leukemia:

• Patient outcomes (efficacy/safety) of ponatinib in 2nd or 3rd line
• Effective implementation of response-based dosing (45mg --> 15mg upon BCR::ABL1 less than 1%) as measured by efficacy and safety
• Post-1L asciminib sequencing
• Treatment free remission
• Ponatinib after HSCT

Philadelphia Chromosome-Positive – Acute Lymphoblastic Leukemia:

• Pediatric data
• Long-term ponatinib exposure outcomes
• Choice of ponatinib in 1st line with time-to-BCR::ABL1 mutation as endpoint
• T315I outcomes
• Effective implementation of response-based dosing (30mg --> 15mg upon BCR::ABL1 less than 0.01%)
• Ponatinib after HSCT
• CNS relapse

Dengue Disease

• Impact of long-term persistence of dengue symptoms on quality of life and cost to dengue patients and their families; out of pocket financial impact related to dengue borne by families/households

• Studies examining predicted relative morbidity gain (QALY/DALY) in dengue prevention versus other infectious disease preventions

• Impact of socioeconomic factors and urban/rural location on probability of dengue patients to present for medical care

• Epidemiology studies to determine age-specific epidemiology of dengue (such as seroprevalence, incidence, hospitalization rate, dengue under-reporting, prevalence of the different serotypes)

• Burden of dengue on tourism and migration (travelers)

• Dengue vaccine(s) hesitancy among different populations

• Harmonization of dengue surveillance system(s) national or supranational

• Studies to assess sequencing of circulating strains

• Studies to assess the impact of age, prior dengue exposure, prior flavivirus exposure, on outcome to natural dengue infection with each dengue serotype; immune responses associated with asymptomatic dengue exposure

• Studies to assess impact of comorbidities on dengue severity and cost

• Studies to assess the impact of dengue vaccine(s) program implementation on dengue epidemiology

• Impact of climate change on epidemiology of dengue

• Impact of vaccination and vector control programs synergies

• Digital immunization registry (to assess vaccination coverage)