A real-world exploration into clinical outcomes of direct oral anticoagulant therapy in people with chronic kidney disease: a large hospital-based study.

BACKGROUND: There is limited evidence to support definite clinical outcomes of direct oral anticoagulant (DOAC) therapy in chronic kidney disease (CKD). By identifying the important variables associated with clinical outcomes following DOAC administration in patients in different stages of CKD, this study aims to assess this evidence gap. METHODS: An anonymised dataset comprising 97,413 patients receiving DOAC therapy in a tertiary health setting was systematically extracted from the multidimensional electronic health records and prepared for analysis. Machine learning classifiers were applied to the prepared dataset to select the important features which informed covariate selection in multivariate logistic regression analysis. RESULTS: For both CKD and non-CKD DOAC users, features such as length of stay, treatment days, and age were ranked highest for relevance to adverse outcomes like death and stroke. Patients with Stage 3a CKD had significantly higher odds of ischaemic stroke (OR 2.45, 95% Cl: 2.10-2.86; p = 0.001) and lower odds of all-cause mortality (OR 0.87, 95% Cl: 0.79-0.95; p = 0.001) on apixaban therapy. In patients with CKD (Stage 5) receiving apixaban, the odds of death were significantly lowered (OR 0.28, 95% Cl: 0.14-0.58; p = 0.001), while the effect on ischaemic stroke was insignificant. CONCLUSIONS: A positive effect of DOAC therapy was observed in advanced CKD. Key factors influencing clinical outcomes following DOAC administration in patients in different stages of CKD were identified. These are crucial for designing more advanced studies to explore safer and more effective DOAC therapy for the population.

Repurposing rapid diagnostic tests to detect falsified vaccines in supply chains.

Substandard (including degraded) and falsified (SF) vaccines are a relatively neglected issue with serious global implications for public health. This has been highlighted during the rapid and widespread rollout of COVID-19 vaccines. There has been increasing interest in devices to screen for SF non-vaccine medicines including tablets and capsules to empower inspectors and standardise surveillance. However, there has been very limited published research focussed on repurposing or developing new devices for screening for SF vaccines. To our knowledge, rapid diagnostic tests (RDTs) have not been used for this purpose but have important potential for detecting falsified vaccines. We performed a proof-in-principle study to investigate their diagnostic accuracy using a diverse range of RDT-vaccine/falsified vaccine surrogate pairs. In an initial assessment, we demonstrated the utility of four RDTs in detecting seven vaccines. Subsequently, the four RDTs were evaluated by three blinded assessors with seven vaccines and four falsified vaccines surrogates. The results provide preliminary data that RDTs could be used by multiple international organisations, national medicines regulators and vaccine manufacturers/distributors to screen for falsified vaccines in supply chains, aligned with the WHO global 'Prevent, Detect and Respond' strategy.

Direct oral anticoagulants and the risk of adverse clinical outcomes among patients with different body weight categories: a large hospital-based study.

OBJECTIVE: Through predictable pharmacokinetics-including a convenient fixed-dose regimen, direct oral anticoagulants (DOACs) are preferred over previous treatments in anticoagulation for various indications. However, the association between higher body weight and the risk of adverse consequences is not well studied among DOAC users. We aim to explore the association of body weight and adverse clinical outcomes in DOAC users. METHODS: A total of 97,413 anonymised DOAC users in a tertiary care setting were identified following structured queries on the electronic health records (EHRs) to extract the feature-rich anonymised dataset. The prepared dataset was analysed, and the features identified with machine learning (ML) informed the adjustments of covariates in the multivariate regression analysis to examine the association. Kaplan-Meier analysis was performed to evaluate the mortality benefits of DOACs. RESULTS: Among DOAC users, the odds of adverse clinical outcomes, such as clinically relevant non-major bleeding (CRNMB), ischaemic stroke, all-cause mortality, and prolonged hospital stay, were lower in patients with overweight, obesity, or morbid obesity than in patients with normal body weight. The odds of ischaemic stroke (OR 0.42, 95% CI: 0.36-0.88, p = 0.001) and all-cause mortality (OR 0.87, 95% CI: 0.81-0.95, p = 0.001) were lower in patients with morbid obesity than in patients with normal body weight. In the Kaplan-Meier analysis, apixaban was associated with a significantly lower rate of mortality overall and in obesity and overweight subgroups than other DOACs (p < 0.001). However, rivaroxaban performed better than apixaban in the morbid obesity subgroup (p < 0.001). CONCLUSION: This study shows the positive effects of DOAC therapy on clinical outcomes, particularly in patients with high body weight. However, this still needs validation by further studies particularly among patients with morbid obesity.

Intragastric balloons for obesity: critical review of device design, efficacy, tolerability, and unmet clinical needs.

INTRODUCTION: Sustaining a healthy weight is a challenge and obesity, with associated risk of co-morbidities, is a major public health concern. Bariatric surgery has shown a great promise for many where pharmacological and lifestyle interventions failed to work. However, challenges and limitations associated with bariatric surgery has pushed the demand for less invasive, reversible (anatomically) interventions, such as intragastric balloons (IGBs). AREAS COVERED: This review critically appraises IGBs used in the past, present, and those in clinical trials, discussing the device designs, limitations, placement and removal techniques, patient eligibility, efficacy, and safety issues. EXPERT OPINION: Several intragastric balloons were developed over the years that brought excitement to patients and healthcare professionals alike. Albeit good efficacy, there had been several safety issues reported with IGBs such as spontaneous deflation, intestinal occlusion, gut perforation, and mucosal ulcerations. This led to evolution of IGBs design; device material, filling mechanism, fluid type, inflation volume, and further innovations to ease ingestion and removal of device. There are some IGB devices under development aimed to swallow like a conventional pill and excrete naturally through defecation, however, how successful they will be in clinical practice in terms of their efficacy and tolerability remains to be seen in the future.

Innovative method for rapid detection of falsified COVID-19 vaccines through unopened vials using handheld Spatially Offset Raman Spectroscopy (SORS).

Preventing, detecting, and responding to substandard and falsified vaccines is of critical importance for ensuring the safety, efficacy, and public trust in vaccines. This is of heightened importance in context of public health crisis, such as the COVID-19 pandemic, in which extreme world-wide shortages of vaccines provided a fertile ground for exploitation by falsifiers. Here, a proof-of-concept study explored the feasibility of using a handheld Spatially Offset Raman Spectroscopy (SORS) device to authenticate COVID-19 vaccines through rapid analysis of unopened vaccine vials. The results show that SORS can verify the chemical identity of dominant excipients non-invasively through vaccine vial walls. The ability of SORS to identify potentially falsified COVID-19 vaccines was demonstrated by measurement of surrogates for falsified vaccines contained in vaccine vials. In all cases studied, the SORS technique was able to differentiate between surrogate samples from the genuine COVISHIELD™ vaccine. The genuine vaccines tested included samples from six batches across two manufacturing sites to account for any potential variations between batches or manufacturing sites. Batch and manufacturing site variations were insignificant. In conjunction with existing security features, for example on labels and packaging, SORS provided an intrinsic molecular fingerprint of the dominant excipients of the vaccines. The technique could be extended to other COVID-19 and non-COVID-19 vaccines, as well as other liquid medicines. As handheld and portable SORS devices are commercially available and widely used for other purposes, such as airport security, they are rapidly deployable non-invasive screening tools for vaccine authentication.

A Real-World Exploration into Clinical Outcomes of Direct Oral Anticoagulant Dosing Regimens in Morbidly Obese Patients Using Data-Driven Approaches.

INTRODUCTION: The clinical outcomes of direct oral anticoagulant (DOAC) dosage regimens in morbid obesity are uncertain due to limited clinical evidence. This study seeks to bridge this evidence gap by identifying the factors associated with clinical outcomes following the dosing of DOACs in morbidly obese patients. METHOD: A data-driven observational study was carried out using supervised machine learning (ML) models with a dataset extracted from electronic health records and preprocessed. Following 70%:30% partitioning of the overall dataset via stratified sampling, the selected ML classifiers (e.g., random forest, decision trees, bootstrap aggregation) were applied to the training dataset (70%). The outcomes of the models were evaluated against the test dataset (30%). Multivariate regression analysis explored the association between DOAC regimens and clinical outcomes. RESULTS: A sample of 4,275 morbidly obese patients was extracted and analysed. The decision trees, random forest, and bootstrap aggregation classifiers achieved acceptable (excellent) values of precision, recall, and F1 scores in terms of their contribution to clinical outcomes. The length of stay, treatment days, and age were ranked highest for relevance to mortality and stroke. Among DOAC regimens, apixaban 2.5 mg twice daily ranked highest for its association with mortality, increasing the mortality risk by 43% (odds ratio [OR] 1.430, 95% confidence interval [CI] 1.181-1.732, p = 0.001). On the other hand, apixaban 5 mg twice daily reduced the odds of mortality by 25% (OR 0.751, 95% CI 0.632-0.905, p = 0.003) but increased the odds of stroke events. No clinically relevant non-major bleeding events occurred in this group. CONCLUSION: Data-driven approaches can identify key factors associated with clinical outcomes following the dosing of DOACs in morbidly obese patients. This will help design further studies to explore well tolerated and effective DOAC doses for morbidly obese patients.

Challenges and Possible Solutions to Direct-Acting Oral Anticoagulants (DOACs) Dosing in Patients with Extreme Bodyweight and Renal Impairment.

This article aims to highlight the dosing issues of direct oral anticoagulants (DOACs) in patients with renal impairment and/or obesity in an attempt to develop solutions employing advanced data-driven techniques. DOACs have become widely accepted by clinicians worldwide because of their superior clinical profiles, more predictable pharmacokinetics, and hence more convenient dosing relative to other anticoagulants. However, the optimal dosing of DOACs in extreme bodyweight  patients and patients with renal impairment is difficult to achieve using the conventional dosing approach. The standard dosing approach (fixed-dose) is based on limited data from clinical studies. The existing formulae (models) for determining the appropriate doses for these patient groups leads to suboptimal dosing. This problem of mis-dosing is worsened by the lack of standardized laboratory parameters for monitoring the exposure to DOACs in renal failure and extreme bodyweight patients. Model-informed precision dosing (MIPD) encompasses a range of techniques like machine learning and pharmacometrics modelling, which could uncover key variables and relationships as well as shed more light on the pharmacokinetics and pharmacodynamics of DOACs in patients with extreme bodyweight or renal impairment. Ultimately, this individualized approach-if implemented in clinical practice-could optimise dosing for the DOACs for better safety and efficacy.

A leap towards enforcing medicines prescribing by generic names in low- and middle-income countries (LMICs): pitfalls, limitations, and recommendations for local drug regulatory agencies.

The Drug Regulatory Authority of Pakistan (DRAP) in response to the public outcry on increasing medicines prices in the country issued notifications to direct healthcare professionals to prescribe medicines with their generic names. Like DRAP, many regulators in the low- and middle-income countries (LMICs) are also inspiring from the west to legally enforce generic prescribing in a bid to reduce the out-of-pocket public expenditures. However, there are pitfalls in the LMICs drug regulatory framework, which if left unaddressed can severely jeopardise the foreseen benefits of medicines prescribing by generic names. This article critically appraises the impact of prescribing by generic names regulations in LMICs and highlights the key considerations that are vital to address before legally enforcing generic prescribing. The ethics, regulatory compliance, and good governance are the key to success; better generics for a better tomorrow.

Sex-specific effects of excipients on oral drug bioavailability.

The mechanism of action of excipients eliciting sex differences in drug bioavailability is poorly understood. In this study, the excipients Cremophor RH 40 (PEG 40 hydrogenated castor oil), Poloxamer 188 (2-methyloxirane) and Tween 80 (polyoxyethylene (80) sorbitan monooleate) were screened at 0.07 - 5% concentrations for their effect on ranitidine bioavailability in male and female Wistar rats. We show that all excipient concentrations significantly increased ranitidine bioavailability in male, but not female, rats. The effect of these excipients on the intestinal efflux transporters P-glycoprotein (P-gp), breast cancer resistant protein (BCRP) and multi-drug resistant protein 2 (MRP2) were also monitored. Measured by ELISA assay, in male rats, peak reductions in intestinal P-gp protein expression occurred in the presence of 1% Cremophor RH 40 and Poloxamer 188 and 0.5% Tween 80. In contrast, no distinct changes were observed in female intestinal P-gp expression. Unlike P-gp, all excipients had a positive effect on MRP2 protein expression - albeit only in males - in a concentration-dependent manner. The excipients did not modulate intestinal BCRP protein expression in either sex. Endogenous hormones and a nuclear receptor (testosterone, oestradiol and pregnane X receptor; PXR) that are purported to regulate intestinal efflux membrane transporter expression were also quantified. In the presence of all excipients, testosterone levels significantly elevated in males, although PXR levels reduced at similar rates in both sexes. No significant effects were identified in oestradiol levels in male and female rats. It is clear that excipients are not inert and their pathway for modulating drug response is multi-dimensional and specific between sexes. This study showed that excipients increased drug bioavailability of a P-gp drug substrate due to its reductive effect on intestinal P-gp expression; we propose that this link may be due to the excipients modulating fundamental testosterone levels. Understanding the implication of excipients on intestinal physiology and hormone levels can therefore improve pharmaceutical design, clinical efficacy and instigate next generation personalised, sex-specific formulations.

COVID-19 Vaccine Hesitancy among Pregnant Women Attending Antenatal Clinics in Pakistan: A Multicentric, Prospective, Survey-Based Study.

This study aimed to assess the vaccination status and factors contributing to vaccine hesitancy among pregnant women in the largest province of Pakistan. A multicentric, prospective, survey-based study using an interviewer-administered tool was conducted among pregnant women attending antenatal clinics between 1 December 2021 through 30 January 2022 across seven hospitals in Pakistan. The healthcare professionals providing care at the participating hospitals administered the survey. Four hundred and five pregnant women fully consented and completed the study. The majority of the study participants (70.6%, n = 286) were aged between 25 and 34 and had a previous successful pregnancy history. More than half of the study participants (56.0%, n = 227) did not receive COVID-19 vaccination at the time of data collection despite their family members (93.9%, n = 372) had already received at least one dose of COVID-19 vaccine. Among those who received COVID-19 vaccination (n = 173), vaccine efficacy, protection for the foetus, and risk of COVID-19-associated hospitalisation were the main driving factors for vaccine hesitancy. The majority of the unvaccinated women (77.8%, n = 182) had no intention of receiving the vaccine. However, more than two-thirds (85.7%, n = 342) consulted the doctor about COVID-19 vaccines, and most were recommended to receive COVID-19 vaccines by the doctors (80.7%, n = 280). Women were significantly more likely to be vaccinated if they had employment (odds ratio [OR] 4.47, 95% confidence interval [CI]: 2.31-8.64) compared with their counterparts who were homemakers, consulted their doctors (OR 0.12, 95% CI: 0.04-0.35), and if they did not have pregnancy-related issues (OR 6.02, 95% CI: 2.36-15.33). In this study, vaccine hesitancy was prevalent, and vaccine uptake was low among pregnant women. Education and employment did impact COVID vaccination uptake, emphasising the need for more targeted efforts to enhance the trust in vaccines.

"Sehat Sahulat Program": A Leap into the Universal Health Coverage in Pakistan.

Universal Health Coverage (UHC), initiative from the World Health Organization (WHO), is a means to provide the human right to health by providing essential health services to everyone, enabling disease prevention, treatment, rehabilitation, and palliative care. In line with the WHO recommendations, the UHC was first introduced in Pakistan in Khyber Pakhtunkhwa (KP) province under the name 'Sehat Sahulat Programme' (SSP), literally 'Health Facility Program' in 2015. The provincial Government in Punjab approved a similar initiative in Punjab, the largest province (by population) of the country, and the program was later rolled out in Islamabad Capital Territory (ICT), Azad and Jammu Kashmir (AJK), Gilgit Baltistan (GB), Sindh, and Baluchistan provinces leaping into the nation-wide coverage. This article provides a current overview of the UHC initiative in Pakistan, analyses its progress in appraising key milestones, and makes recommendations to achieve a robust universal health coverage across Pakistan.

Comment on Aldén et al. Intracellular Reverse Transcription of Pfizer BioNTech COVID-19 mRNA Vaccine BNT162b2 In Vitro in Human Liver Cell Line. Curr. Issues Mol. Biol. 2022, 44, 1115-1126.

Aldén et al. (2022) recently reported the intracellular reverse transcription of Pfizer BioNTech COVID-19 mRNA Vaccine BNT162b2 in vitro in a human liver cell line (Huh7) [...].

A dengue-like outbreak of unknown aetiology in Pakistan.

There were recent reports of a mysterious virus spreading in Pakistan causing dengue-like illness with hundreds of cases admitted to hospitals over the winter. The mysterious virus was touted as a new variant of the dengue virus by the local health experts in Pakistan as most patients were tested negative for the dengue virus test despite presenting with dengue-like symptoms. In this letter, we have critically appraised the current situation in Pakistan in an attempt to explain the science and mechanism behind recent dengue-like outbreak, offered suggestions on diagnostic tests and provided recommendations to improve medication safety in Pakistan.

Why COVID vaccines for young children (5-11 years) are not essential at this moment in time?

The Joint Committee on Vaccination and Immunisation (JCVI) in UK has recently advised that COVID vaccines in 5-11-year-old children is non-essential. This has created an outrage among some healthcare professionals who believed a mandatory vaccination program for all ages would be more beneficial. The JCVI decision sounds strange to many public health professionals in light of the existing practices with regards to other children's vaccines, for instance flu jabs. The child immunisation should help reduce suffering in children, prevent virus spread in communities, reduce school off days, prevent the loss of quality of life in children and the sufferings from a preventable infection. Therefore, why not support essential COVID vaccines for young children like we do for the flu? This article explains the underlying mechanisms of currently deployed COVID vaccines, the cellular, humoral and mucosal immunity. The article explains why we should not rush mass-immunising young children and a delayed immunisation can be beneficial in offering a more suitable vaccine formulation for children, such as the nasal COVID vaccine, that is going to be available soon and will provide the sought-after protection against infection and transmission,  the public health benefit from the mass immunisation program in children.

Potential applications and performance of machine learning techniques and algorithms in clinical practice: A systematic review.

PURPOSE: The advent of clinically adapted machine learning algorithms can solve numerous problems ranging from disease diagnosis and prognosis to therapy recommendations. This systematic review examines the performance of machine learning (ML) algorithms and evaluates the progress made to date towards their implementation in clinical practice. METHODS: Systematic searching of databases (PubMed, MEDLINE, Scopus, Google Scholar, Cochrane Library and WHO Covid-19 database) to identify original articles published between January 2011 and October 2021. Studies reporting ML techniques in clinical practice involving humans and ML algorithms with a performance metric were considered. RESULTS: Of 873 unique articles identified, 36 studies were eligible for inclusion. The XGBoost (extreme gradient boosting) algorithm showed the highest potential for clinical applications (n = 7 studies); this was followed jointly by random forest algorithm, logistic regression, and the support vector machine, respectively (n = 5 studies). Prediction of outcomes (n = 33), in particular Inflammatory diseases (n = 7) received the most attention followed by cancer and neuropsychiatric disorders (n = 5 for each) and Covid-19 (n = 4). Thirty-three out of the thirty-six included studies passed more than 50% of the selected quality assessment criteria in the TRIPOD checklist. In contrast, none of the studies could achieve an ideal overall bias rating of 'low' based on the PROBAST checklist. In contrast, only three studies showed evidence of the deployment of ML algorithm(s) in clinical practice. CONCLUSIONS: ML is potentially a reliable tool for clinical decision support. Although advocated widely in clinical practice, work is still in progress to validate clinically adapted ML algorithms. Improving quality standards, transparency, and interpretability of ML models will further lower the barriers to acceptability.

Covid-19 Vaccine safety and adverse event analysis from Pakistan.

Covid immunization commenced on 2nd Feb 2021 in Pakistan and as of 7th Sep 2021, over 84 million vaccine doses were administered in Pakistan, of which 72% procured by the government, 22% received through Covax and 6% were donated. The vaccines rolled out nationally included: Sinopharm, Sinovac and CanSinoBIO (China), AstraZeneca (UK), Moderna and Pfizer (USA), Sputnik (Russia), and PakVac (China/Pakistan). About half of the eligible population in Pakistan (63 m) had received at least one dose of Covid vaccine as of Sep 2021. Pakistan National Pharmacovigilance Centre (PNPC) in coordination with WHO, MHRA and Uppsala Monitoring Centre (UMC) established pharmacovigilance centers across Pakistan. The Covid vaccine AEFIs in Pakistan were mainly reported via NIMS (National Immunization Management System), COVIM (Covid-19 Vaccine Inventory Management System), 1166 freephone helpline and MedSafety. There have been 39,291 ADRs reported as of 30th Sept 2021, where most reported after the first dose (n = 27,108) and within 24-72 h of immunization (n = 27,591). Fever or shivering accounted for most AEFI (35%) followed by injection-site pain or redness (28%), headache (26%), nausea/vomiting (4%), and diarrhoea (3%). 24 serious AEFIs were also reported and investigated in detail by the National AEFI review committee. The rate of AEFIs reports ranged from 0.27 to 0.79 per 1000 for various Covid vaccines in Pakistan that was significantly lower than the rates in UK (∼4 per 1000), primarily atrributed to underreporting of cases in Pakistan. Finally, Covid vaccines were well tolerated and no significant cause for concern was flagged up in Pakistan's Covid vaccine surveillance system concluding overall benefits outweighed risks.

Lactoferrin reduces the risk of respiratory tract infections: A meta-analysis of randomized controlled trials.

BACKGROUND: Lactoferrin (Lf) is one of the key immunomodulatory substances found naturally in various body fluids, such as saliva, tears, and breast milk, and forms a vital part of the innate defense against invading pathogens. Various studies have demonstrated antibacterial, antifungal, and antiviral properties of Lf and its protective role against respiratory tract infections (RTIs). The present meta-analysis aims to elucidate the association of Lf administration in reducing the risk of RTIs by systematically reviewing the data from randomized controlled trials (RCTs). METHODS: We systematically searched PubMed, Cochrane Library, Medline & CINAHL, Turning Research into Practice (TRIP), ProQuest Theses & Dissertations Databases, and China National Knowledge Infrastructure (CNKI) from inception till March 15, 2021. The primary outcome measure was a reduction in respiratory illness; decrease in frequency, symptoms, and duration. Random-effects model was used to estimate the odds ratio (OR) and 95% confidence interval (CI). We used Cochrane's RoB-2 to appraise the risk of bias of included RCTs. RESULTS: A total of nine RCTs were eligible for this review, of which six were included in the meta-analysis. Overall, two studies demonstrated a high risk of bias. The meta-analysis revealed a significantly reduced odds of developing respiratory infections with the use of Lf relative to the control (pooled odds ratio = 0.57; 95% confidence interval 0.44 to 0.74, n = 1,194), with sufficient evidence against the hypothesis of 'no significant difference' at the current sample size. CONCLUSIONS: The administration of Lf shows promising efficacy in reducing the risk of RTIs. Current evidence also favours Lf fortification of infant formula. Lf may also have a beneficial role in managing symptoms and recovery of patients suffering from RTIs and may have potential for use as an adjunct in COVID-19, however this warrants further evidence from a large well-designed RCT.

Does methylprednisolone reduce the mortality risk in hospitalized COVID-19 patients? A meta-analysis of randomized control trials.

Objectives: The question remained if mortality benefits with dexamethasone seen in patients with coronavirus disease 2019 (COVID-19) also extend to other systemic corticosteroids such as methylprednisolone. This article presents a meta-analysis of randomized controlled trials (RCTs) to ascertain if methylprednisolone can be recommended for use in patients with COVID-19 to prevent deaths.Methods: Systematic literature search was performed in PubMed, Scopus, Cochrane Central Register of Controlled Trials, and preprint servers until 13 April 2021. The outcome of interest was all-cause mortality. The random-effects model for the meta-analysis was utilized to estimate the pooled odds ratio (OR) at 95% confidence intervals (CI).Results: Five RCTs were included in the meta-analysis. The pooled OR for all-cause mortality was 0.64 (95% CI: 0.29 - 1.43, n = 652) comparing methylprednisolone with the control, indicating no mortality benefits. A similar finding was noted with a sub-group analysis including four trials that used low-dose methylprednisolone. However, the only trial that administered high dose methylprednisolone indicated a statistically significant mortality benefit (OR 0.08, 95% CI: 0.02-0.42).Conclusions: In determining equipotent doses for an acute short-course pulse therapy of corticosteroids, the biological half-life of steroids should also be accounted for besides the potency factor. A short duration (3-5 days) pulse therapy of high-dose methylprednisolone can be a promising alternative to the low-dose dexamethasone therapy in severely ill patients with COVID-19 to prevent deaths.

Let's talk about sex: Differences in drug therapy in males and females.

Professor Henry Higgins in My Fair Lady said, 'Why can't a woman be more like a man?' Perhaps unintended, such narration extends to the reality of current drug development. A clear sex-gap exists in pharmaceutical research spanning from preclinical studies, clinical trials to post-marketing surveillance with a bias towards males. Consequently, women experience adverse drug reactions from approved drug products more often than men. Distinct differences in pharmaceutical response across drug classes and the lack of understanding of disease pathophysiology also exists between the sexes, often leading to suboptimal drug therapy in women. This review explores the influence of sex as a biological variable in drug delivery, pharmacokinetic response and overall efficacy in the context of pharmaceutical research and practice in the clinic. Prospective recommendations are provided to guide researchers towards the consideration of sex differences in methodologies and analyses. The promotion of disaggregating data according to sex to strengthen scientific rigour, encouraging innovation through the personalisation of medicines and adopting machine learning algorithms is vital for optimised drug development in the sexes and population health equity.