Open research questions in Pharmaceutical studies and practices
28 unresolved questions extracted from the limitations and future-work sections of 393 Pharmaceutical studies and practices papers in our library. Each links back to the study that raised it.
What the literature leaves open
In infancy, medication costs typically accounted for less than 15% of total healthcare expenditure in studies reporting both components; childhood evidence was limited and suggested a smaller share of total costs.
Background: Therapeutic drug monitoring (TDM) helps optimize pharmacotherapy, but research activity in low- and middle-income countries (LMICs) is poorly characterized.
Mapping Therapeutic Drug Monitoring Research in Low- and Middle-Income Countries: A Scoping Review (2015–2024) · 2026 · DOIABSTRACT Antimicrobial use among children in Japan has declined substantially; however, tetracycline use has increased among adolescents, particularly after 2017 and during the COVID‐19 period, and the underlying clinical indications remain unclear.
Oral Tetracycline Use in Children and Adolescents in Japan: Trends, Indications, and Treatment Patterns · 2026 · DOIPharmacopsychiatry molar units to relate concentration to dose. Laboratories vary in the presentation of their results. They should always add the reference for the reference range to the result. The clinician should take note of the units (i. e., ng/mL, μg/L, μmol/L, or nmol/L) in which the results of the analysis are expressed. This is especially recommended for comparisons of values obtained from different laboratories or with those in the literature. To transform molar units into mass units and vice versa, conversion factors are given in Table 5. When drug concentrations are below the lower limit of quantification, which refers to the lowest concentration of the standard curve that can be measured with at least 80–120 % accuracy and 20 % precision, this limit should be indicated.1561 The results should be available for decision making within a clinically meaningful time. A 24 hours TDM service is desirable; however, a 48 hours turnaround time is sufficient in most cases. In the case of suspected intoxications, a few hours service is necessary.1391 To assist rapid intervention in patients at risk for toxicity or loss of tolerability, prompt information of the treating physician (i. e., a phone call) is required when the laboratory measures drug concentrations above the laboratory alert level (Table 5). We highly recommend that interpretation and pharmacological or pharmaceutical advice are provided with every assessment of a drug concentration, not only for those outside the therapeutic range. Expert interpretation and the adequate use of the information are essential to ensure the full clinical benefit of the TDM report. Reporting of results with inclusion of dose recommendations and other comments must be guided by the best available evidence. As shown in Fig. 4, it is important to check what the indication for TDM was, if the steady state was reached, if the through concentration was measured and what the level of recommendation was to draw correct clinical conclusions from the results. Expert knowledge may be necessary to calculate dose corrections or analyze drug–drug interactions. It is advantageous for the clinician to choose a laboratory that offers this service. Otherwise, the treating physician, a clinical pharmacologist or a trained expert of the clinic has to interpret the results and check for drug interactions that might explain the results. Access to specialist advice is also necessary if TDM results suggest that genotyping may be advisable, as shown in Fig. 5. It may even be legally required to include collaboration with a clinical pharmacologist. In Switzerland, a psychiatrist or a pharmacist may prescribe CYP genotyping, but it will only be reimbursed by insurances, when the test is prescribed by a physician specialized in clinical pharmacology.
Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2026 – Pharmacokinetic, pharmacogenetic and clinical aspects · 2026 · DOIWe recommend regular monitoring of drug concentrations in blood under maintenance therapy, at least every 3–6 months, to prevent relapses and re-hospitalizations. The frequency of TDM requests may be increased if the patient is suspected to be non-adherent to the medication or in the case of changes of co-medications or smoking that affect the pharmacokinetics of the prescribed drug. Patients with Parkinsons’s disease Parkinson’s disease (PD) is the second most common neurodegen- erative disease and is typically associated with progressive motor dysfunction, although PD patients also exhibit a variety of non-mo- tor symptoms. The mainstay of symptomatic treatment is dopa- mine replacement using levodopa (l-DOPA and l-3,4-dihydroxy- phenylalanine) in combination with decarboxylase inhibitors (benserazide and carbidopa) and catechol-O-methyltransferase (COMT) inhibitors (entacapone, opicapone, and tolcapone) or monoamine oxidase, type B (MAO-B), inhibitors (rasagiline, safi- namide, and selegiline) and dopamine receptor agonists (for ex- ample apomorphine, pramipexole, ropinirole, and rotigotine). However, the emergence of motor complications, such as the wear- ing-off phenomenon, remains a significant clinical challenge. Therefore, repeated individual adjustments of dopamine-replace- ment therapies are required throughout the course of the disease © 2026. The Author(s).Hart XM et al. doi: 10.1055/a-2860-7861 due to ongoing neurodegeneration. Both primary symptoms and motor complications have been key targets in the development of improved symptomatic treatments for PD. Recent progression in the management of motor complications is supported by newly developed agents and improvements in device and formulation technologies that enable continuous drug delivery (e.g., extend- ed-release formulations of levodopa, new intrajejunal or subcuta- neous and inhalation formulations of levodopa). TDM of dopamine-replacement drugs has the potential to op- timize therapy on an individualized basis and improve both effica- cy and tolerability. This was suggested to establish TDM of levodo- pa, still the gold standard for treatment of PD, as an initial step.990 The complex pharmacology of levodopa is influenced by its short t1/2, the gastric emptying velocity, body weight, combination with inhibitors of levodopa metabolizing enzymes, and the progression of PD (see ref. 990 ). These factors considerably contribute to the observed variability of plasma concentrations of levodopa and its metabolite 3-O-methyldopa. Both amino acids compete with other aromatic amino acids as well as branched chain amino acids in pro- tein-rich meals on the limited transport capacity in the gastrointes- tinal tract and the BBB. Hence, levodopa measurements may allow insights into the phenomenon of inappropriate levodopa response. Furthermore, they can uncover the lack of compliance and potential interactions with treatments for other mainly age-related disorders, like hypertension, diabetes, hyperlipidemia, rheumatism and OTC herbal medicines. Finally, TDM may enable clinicians to better dis- tinguish between branded and generic levodopa formulations. Recommendations for determining drug concentra- tions in neuropsychiatric drugs The utility of TDM depends on the specific clinical context and the characteristics of the drug being monitored. In situations where non-adherence or incomplete adherence to medication is suspect- ed, or in cases of intoxication, measuring drug concentrations in blood plasma or serum is widely recognized as a valuable tool across all drug types and patient populations. Nevertheless, the integration of TDM into routine clinical practice remains a subject of debate in many countries. Drawing from empirical evidence, recommendations for the implementation of TDM have been cat- egorized into four levels, ranging from “strongly recommended” to “potentially useful” as outlined below: Level 1: Strongly recommended Evidence: Established therapeutic reference ranges exist. Controlled clinical trials have demonstrated the benefits of TDM. Reports of decreased tolerability or intoxications are available. Recommendation: Obligatory TDM is strongly recommended for dose titration and addressing specific indications. For example, TDM is considered a standard practice for drugs like lithium and carbamazepine. Clinical consequences: Optimal therapeutic responses are expected within reported therapeutic reference ranges. Subtherapeutic concentrations may result in responses similar to a placebo during acute treatment and risk relapse during chronic treatment. Suprath- erapeutic concentrations increase the likelihood of adverse reactions or toxicity.
Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2026 – Pharmacokinetic, pharmacogenetic and clinical aspects · 2026 · DOIMeasuring the drug concentration in blood serum or plasma once the patient has achieved the desired clinical outcome can provide valuable insights. This concentration can be considered the optimal level for the individual patient. If there is a recurrence of symptoms, relapse, or adverse drug reactions, this value can help determine whether non-adherence or pharmacokinetic changes have occurred, potentially explaining the clinical deterioration.
Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2026 – Pharmacokinetic, pharmacogenetic and clinical aspects · 2026 · DOIAs long as valid data on therapeutic reference ranges do not exist, we recommend the determination of the 25th and 75th percentile of drug concentrations in blood plasma or serum of responders to the neuropsychiatric medication. This range should be used as a preliminary therapeutic reference range. Further (prospective or observational) studies must verify or correct this range.
Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2026 – Pharmacokinetic, pharmacogenetic and clinical aspects · 2026 · DOIThe high relative standard deviation (66.58% for left halves, 72.32% for right halves) indicates poor mechanical strength requiring further research into formulation variables affecting tablet splitting uniformity.
The study did not assess the clinical implications of altered pharmacokinetics resulting from drastic reduction in disintegration time (92 to 32 seconds) on plasma levels and therapeutic efficacy in actual patient populations.
Urgent optimization of the formulation or manufacturing process is necessary to ensure structural integrity and reduce friability beyond the current 8.94% mean.
The review found that medication costs for common complications varied widely, with higher costs associated with severe conditions and specific treatments.
The mechanism by which high baseline friability causes excessive fragmentation and mass loss during subdivision requires further theoretical investigation.
The paper identifies the accelerating problem of bacterial resistance and diminishing antimicrobial resources but does not provide comprehensive strategies or future directions for addressing these challenges through optimized off-label prescribing.
<i>Conclusions:</i> Physicians’ baseline awareness of ACE inhibitor, ARB, or statin teratogenic risks and risk documentation was lacking.
INTRODUCTION: The presence of liver cirrhosis can have a major impact on pharmacodynamics and pharmacokinetics, but guidance for prescribing is lacking.
Evidence-Based Recommendations to Improve the Safe Use of Drugs in Patients with Liver Cirrhosis · 2018 · DOIPrescribers should take into account that PPI uses pose toxicity risks, which remain to be fully characterised in infants and children.
BACKGROUND: Oral naltrexone is effective in the treatment of alcohol dependence; however, a major limitation of its clinical utility is poor patient adherence to the daily dosing schedule.
Most-cited papers in Pharmaceutical studies and practices
- Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old · PEDIATRICS · 2021 · 410 citations
- Computerized Physician Order Entry and Medication Errors in a Pediatric Critical Care Unit · PEDIATRICS · 2004 · 287 citations
- Unlicensed and off label prescribing of drugs in general practice · Archives of Disease in Childhood · 2000 · 148 citations
- Children are not COVID-19 super spreaders: time to go back to school · Archives of Disease in Childhood · 2020 · 146 citations
- Single‐ and Multiple‐Dose Pharmacokinetics of Long‐acting Injectable Naltrexone · Alcoholism Clinical and Experimental Research · 2006 · 109 citations
- Vancomycin continuous infusion in neonates: dosing optimisation and therapeutic drug monitoring · Archives of Disease in Childhood · 2012 · 106 citations
- Toxicity of long-term use of proton pump inhibitors in children · Archives of Disease in Childhood · 2017 · 92 citations
- Prescription information leaflets: a pilot study in general practice. · BMJ · 1983 · 74 citations
- Developing a paediatric drug formulary for the Netherlands · Archives of Disease in Childhood · 2016 · 73 citations
- Double checking the administration of medicines: what is the evidence? A systematic review · Archives of Disease in Childhood · 2012 · 72 citations
Most recent work
- Evaluation of drugs and risk factors requiring therapeutic drug monitoring in the Neonatal Intensive Care Unit: a retrospective study · BMC Pediatrics · 2026
- Exploring the Practice and Implications of Tablet Splitting in Pharmaceutical Care · Journal of Drug Delivery and Therapeutics · 2026
- Closing the Evidence Gap for Drugs in Children — Measures to Strengthen the Pediatric Research Equity Act · New England Journal of Medicine · 2026
- Double Dose of Prescription Medicines, Overuse or Un necessary use of OTC Medicines, Supplements & its Role of Social Medias in the Gulf & Middle East Countries · PriMera Scientific Medicine and Public Health · 2026
- Post‐Approval Pediatric Use of Drugs Granted Waivers from Pediatric Testing · Clinical Pharmacology & Therapeutics · 2026
- Simulated Y‐Site Compatibility of Calcium Gluconate and Benzylpenicillin With Maintenance Fluid Used in Neonatal Intensive Care Unit · Clinical and Translational Science · 2026
- Sponsor Initiated Requests to Delay Pediatric Postmarketing Studies · Pharmaceutical Medicine · 2026
- Evaluating a virtual paediatric adverse drug reaction clinic · British Journal of Clinical Pharmacology · 2026
- "Dual-Unit Chocolate-Coated Placebo Delivery System for Pediatric Compliance" · Zenodo (CERN European Organization for Nuclear Research) · 2026
- Piperacillin Population Pharmacokinetics in Plasma and Peritoneal Fluid and Dosing Optimization in Children Undergoing Liver Transplant: An Optimome Study · Clinical Pharmacology & Therapeutics · 2026
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