Participants stopped meals three hours before bed, dimmed the lights and extended their overnight fast by two hours
Photo by Cottonbro on Pexels
A new Northwestern Medicine study has personalised overnight fasting by aligning it with individuals’ circadian sleep-wake rhythm, an important regulator of cardiovascular and metabolic function, all without changing their caloric intake.
The study found that among middle-age and older adults who are at higher risk for cardiometabolic disease, extending the participants’ overnight fast by about two hours, dimming the lights and not eating for three hours prior to bedtime improved measures of cardiovascular and metabolic health during sleep, as well as during the daytime. Nighttime blood pressure fell by 3.5mmHg while heart rate dipped by 5% compared to controls. while adherence was good – nearly 90%.
“Timing our fasting window to work with the body’s natural wake-sleep rhythms can improve the coordination between the heart, metabolism and sleep, all of which work together to protect cardiovascular health,” said first author Dr. Daniela Grimaldi, research associate professor of neurology in the division of sleep medicine at Northwestern University Feinberg School of Medicine.
“It’s not only how much and what you eat, but also when you eat relative to sleep that is important for the physiological benefits of time-restricted eating,” said corresponding author Dr Phyllis Zee, director of the Center for Circadian and Sleep Medicine and the chief of sleep medicine in the department of neurology at Feinberg.
Previous research has found only 6.8% of US adults had optimal cardiometabolic health in 2017 to 2018. Poor cardiometabolic health can lead to chronic illness, including type 2 diabetes, non-alcoholic fatty liver disease and cardiovascular diseases.
Time-restricted eating has continued to surge in popularity because research has shown it can improve cardiometabolic health and rival traditional calorie‑restricted diets, but most studies have focused on how long people fast, not how their fast lines up with their sleep schedule – a key factor in metabolic regulation.
Given the nearly 90% adherence rate in the study, the study’s novel approach of leveraging the sleep period as an anchor for the timing of time-restricted eating may be a more accessible non-pharmacological strategy for improving cardiometabolic health, particularly in middle-aged and older adults who are at higher risk for cardiometabolic disease, the study authors said.
The study authors said they plan refine the protocol from this study and take it to larger multi-centre trials.
Improved blood pressure, heart rate, blood-sugar control
In the 7.5‑week study, people who finished eating at least three hours before going to bed saw meaningful improvements compared with those who kept their usual eating routines. They experienced:
Improved nighttime patterns in blood pressure (dipping by 3.5%) and heart rate (dipping by 5%): Their bodies showed a more natural drop in both measures during sleep, which is an important sign of cardiovascular health. Notably, their hearts beat faster during the day when they were active and slowed at night when they were resting. A stronger day-night pattern is linked to better cardiovascular health.
Better daytime blood‑sugar control: Their pancreas responded more efficiently when challenged with glucose, suggesting it could release insulin more effectively and keep blood sugar steadier.
In the study, 39 overweight/obese participants (36 to 75 years old) completed either an extended overnight fasting intervention (13 to 16 hours of fasting) or a control condition (habitual fast of 11 to 13 hours). Both groups dimmed the lights three hours before bedtime. The intervention group consisted of 80% women.
Retina showing reticular pseudodrusen. Although they can infrequently appear in individuals with no other apparent pathology, their highest rates of occurrence are in association with age-related macular degeneration (AMD), for which they hold clinical significance by being highly correlated with end-stage disease sub-types, choroidal neovascularisation and geographic atrophy. Credit: National Eye Institute
Doctors have found further evidence that metformin is associated with less progression of age-related macular degeneration (AMD), the most common cause of blindness in Western countries. In a study of over 2000 people with diabetes, people over the age of 55 years taking metformin were 37% less likely to develop the intermediate stage of AMD over five years compared to those not taking metformin. The results were published in BMJ Open Ophthalmology.
AMD is a disease which affects the central retina or macular at the back of the eye. It eventually causes the light-sensitive tissue to die off (geographic atrophy, a form of ‘dry’ AMD) or be damaged by abnormal blood vessel growth (‘wet’ AMD). Intermediate and advanced AMD affects 10-15% of people over 65 years of age (1.1 to 1.8 million people in the UK), and is the commonest cause of blindness in high-income countries.
The annual cost of AMD is estimated to be £11.1billion in the UK. Geographic atrophy has no treatment in the UK and Europe, while treatments for wet AMD are expensive and unpleasant (repeated injections into the eye).
The research from the University of Liverpool used pictures taken of the eyes of 2000 people attending the routine diabetic eye disease screening programme in Liverpool over 5 years. The researchers assessed whether AMD was present on the photographs and how severe it was, and then compared those taking metformin and those who were not. They also adjusted for factors which might bias the result, such as age, sex, and duration of diabetes. The odds of developing intermediate AMD over 5 years in the metformin group was 0.63 compared to the no metformin group (95% confidence range 0.43 to 0.92).
A potential benefit from metformin in AMD has been suspected before, but this is the first study to grade AMD from eye photographs. Previous studies on metformin have used secondary information on AMD such as GP diagnostic codes, or insurance claims in the US.
Dr Nick Beare, an eye doctor who led this research, says: “Most people who suffer from AMD have no treatment, so this is a great breakthrough in our search for new treatments. What we need to do now is test metformin as a treatment for AMD in a clinical trial. Metformin has the potential to save many people’s sight.”
Findings indicate vitamin B3 looks promising to help rearm a compromised immune system
Unrestricted tumour growth in mouse brain, left, compared to the tumour growth in a mouse who received niacin treatment, right (both after 42 days). Courtesy Yong lab
Edward (Ed) Waldner had no idea why he didn’t feel well, but he knew he didn’t feel like himself. At 55 years of age, he felt exhausted all the time. It didn’t seem to matter how hard he had worked that day. He wondered if he had sleep apnoea. He noticed his walking was off. His heels would drag now and again. One day, when his symptoms were worse than usual, he decided to go to the Emergency department.
“The doctor said I had a mass on my brain and needed to see an oncologist,” says Waldner.
The mass was glioblastoma, a deadly brain cancer. Treatment often involves a three-pronged approach: surgery to remove as much of the tumour as possible, followed by radiation and chemotherapy. However, despite advances in cancer treatment, the aggressive cancer comes back.
University of Calgary researchers are investigating whether adding high doses of vitamin B3 or niacin to the treatment plan could be beneficial. They approached Waldner about being in the trial.
“I have no problem trying to help anybody. I agreed. I want to help myself, too,” says Waldner. “I can tell you being part of this research helps me mentally because we’re trying. When I left the hospital after surgery I was told, that’s it, that’s all we can do.”
Hotchkiss, Charbonneau members partner for study
The research is led by two members of both the Hotchkiss Brain Institute and Arnie Charbonneau Cancer Institute – Dr Gloria Roldan Urgoiti, MD, PGME’16, an oncologist specialised in brain cancers, and Dr Wee Yong, PhD, a neuroscientist whose research focuses on immune effects on the brain. Together, they designed a study to investigate whether niacin could rejuvenate compromised immune cells to kill tumour cells. The research began in the Yong lab, with mice, where findings showed niacin prolonged survival. That work evolved into a Phase I and II clinical trial.
“Normally, the immune system will try to counter and prevent tumour growth; however, this brain cancer supresses the immune system,” says Yong, a professor at the Cumming School of Medicine (CSM). “Niacin treatment rejuvenates immune cells so they can do what they are supposed to do, attack and kill the cancer cells. I see it as an ongoing ‘battle for the brain.’”
Studying the benefits of adding niacin to chemotherapy, radiation
The clinical trial was designed to determine the maximum dose and potential benefit of controlled-release niacin that could be added to the recommended chemotherapy and radiotherapy treatments. Researchers decided the study would stop if the progression-free survival over six-months did not improve by at least 20 per cent compared with older studies. Early results involving 24 patients showed 82 per cent of the participants were free of progression of the cancer at six months; an increase of 28 per cent from previous studies. The researchers say this is a promising advancement for this incurable cancer.
“Glioblastoma is the most aggressive brain cancer in adults. Survival of patients with this condition hasn’t changed significantly for 20 years,” says Roldan Urgoiti, a clinical associate professor at the CSM. “Anything that may help should be explored, but it requires strict protocols and safety monitoring.”
The researchers caution that high amounts of vitamins, like niacin, have toxicity and can have a negative impact on someone’s health if not monitored closely by medical professionals.
The team hopes to be able to do the final analysis, that will include 48 participants by the end of 2026 or early 2027.
Waldner says he’s feeling really good these days and is just happy to hear the word “stable” when he goes for his regular scans.
Nurse-led hospital care matches doctor-led care for safety and effectiveness
Photo by Hush Naidoo on Unsplash
Nurses can safely deliver many services traditionally performed by doctors, with little to no difference in deaths, safety events, or how patients felt about their health, according to a new Cochrane review. In some cases, nurse-led care even outperformed doctor-led care.
Healthcare services are facing pressure due to an ageing population, complex health needs, long waiting lists, and doctor shortages. Receiving care from nurses, rather than doctors has been proposed as one way to improve access to hospital services for patients who may otherwise face long waits.
A group of researchers from Ireland, United Kingdom, and Australia evaluated nurse-doctor substitution in inpatient units and outpatient clinics, analysing 82 randomised studies involving over 28 000 patients across 20 countries. Studies included advanced nurse practitioners, clinical nurse specialists and registered nurses substituting for junior or senior doctors across specialties such as cardiology, diabetes, cancer, obstetrics/gynaecology, and rheumatology.
Nurse-led hospital care matches doctor-led care for safety and effectiveness
The review found little to no difference between nurse-led and doctor-led care for critical outcomes, including mortality, quality of life, self-efficacy, and patient safety events. While most clinical outcomes showed no difference between groups, nurses may achieve better outcomes in some areas, including diabetes control, cancer follow-up, and dermatology. Doctor-led care performed slightly better in a small number of sexual health and medical abortion follow-up services.
Our findings show that nurse-led services provide care that is just as safe and effective as doctor-led services for many patients. In some areas, patients actually experienced better outcomes when nurses led their care.
— Professor Michelle Butler,lead author from Dublin City University
The models of substitution varied widely, with different grades of nurses operating autonomously, under supervision, or following specialized protocols. There were also differences in training, level of responsibility, and mode of substitution, all of which may influence outcomes.
Butler added:
In some cases, patients had earlier, more frequent, or on-demand appointments with nurses, or had an additional educational component to their care, which may have helped to improve their outcomes.
Evidence on direct costs was limited and varied across studies, partly due to differences in reporting methods, currencies and time periods. Seventeen studies reported reduced costs for nurse-led care, while nine suggested higher costs due to longer consultations, referrals, or prescription differences.
Not a one-size-fits-all solution
However, nurse-doctor substitution is not a one-size-fits-all approach. The authors caution that these interventions should always be interpreted within context.
Nurse substitution isn’t simply a one-for-one replacement. To work well, these services need the right training, support and models of care, but the evidence shows patients are not disadvantaged and can benefit in meaningful ways.
— Timothy Schultz, senior author and researcher from Flinders Health and Medical Research Institute
Expanding nurse-led services may help address doctor shortages, but the authors urge that policymakers should consider the impact of these interventions on the nursing workforce, including training and organization.
While the evidence base was substantial, the authors note important gaps. Most studies were from high-income countries, with the majority (39%) conducted in the United Kingdom. The authors call for more studies across specialties, nurse roles and patient types not yet evaluated, as well as stronger consistency in how outcomes are measured. They also highlight the need for more research in low- and middle-income countries, where nurse-led roles could potentially improve access to care in regions facing doctor shortages.
Photo by Towfiqu barbhuiya: https://www.pexels.com/photo/person-feeling-pain-in-the-knee-11349880/
Gout is the most common form of inflammatory arthritis, with worldwide prevalence of approximately 4%. The accumulation of monosodium urate crystals in gout leads to the clinical manifestations of the disease and if left inadequately treated, leads to chronic arthritis with joint damage. Due to its anti-inflammatory properties, colchicine, an alkaloid drug derived from the autumn crocus plant, is commonly used in the management of gout for both prophylaxis and treatment of gout flares.
A recent study on colchicine’s potential benefit for cardiovascular disease noted that participants who were taking the drug had fewer joint replacements than those taking a placebo. Since colchicine is commonly used in gout, researchers wondered if colchicine would lower risk of joint replacement in those with gout as well. Further, because osteoarthritis is the most common reason for joint replacement, and because osteoarthritis and gout can occur together, researchers wondered if colchicine could lower the risk of joint replacement in those with both gout and osteoarthritis.
A new study from Boston University Chobanian & Avedisian School of Medicine has found that people with gout who were prescribed colchicine had a modest 12% risk of joint replacement compared to those who did not receive the drug. Additionally, those with both gout and osteoarthritis who took colchicine had a 23% lower risk of needing joint replacement.
While it would have been ideal for a clinical trial to address the question of whether colchicine reduces the need for joint replacement in gout, it was not readily feasible to conduct such a trial of adequate sample size and duration. Therefore, the researchers used real-world evidence from a UK population-based database in which they identified people with gout, and then divided that pool into those who were newly prescribed colchicine and those who were not. They then assessed the frequency of knee and hip replacement in both groups.
According to the researchers, these findings suggest that colchicine may have benefits beyond symptom relief alone. “This observation could have broad implications for duration of colchicine use in gout, which is often limited to just the first six months of getting started on a urate-lowering therapy or limited to treatment of flares,” explains corresponding author Tuhina Neogi, MD, PhD, Professor of Rheumatology and professor of medicine at the school.
Additionally, Neogi believes these findings have implications for potential benefits of colchicine for osteoarthritis irrespective of gout, which is the most common form of arthritis and a leading reason for joint replacement surgery. “Prior trials of colchicine in osteoarthritis have been largely negative, but they likely have been too small and had too short a duration to detect potential effects,” adds Neogi who also is chief of rheumatology at Boston Medical Center.
The results of a phase 3 clinical trial for enlicitide, a novel oral medication designed to lower cholesterol have been reported in a recent New England Journal of Medicine article. The study, involving nearly 3000 adults with existing or at high risk of cardiovascular disease, compared a daily 20mg dose against a placebo over one year.
Researchers found that the drug significantly reduced LDL cholesterol by approximately 57% within 24 weeks, alongside notable decreases in other harmful lipids. These improvements remained consistent and durable throughout the 52-week treatment period. Crucially, the safety profile of the oral inhibitor appeared comparable to the placebo, with no meaningful difference in side effects. The authors conclude that this convenient pill could offer a highly effective alternative to existing injectable therapies for managing heart disease risk.
A new prospective cohort study by investigators from Mass General Brigham and colleagues analysed 131 821 participants from the Nurses’ Health Study (NHS) and Health Professionals Follow-Up Study (HPFS), finding that moderate consumption of caffeinated coffee (2-3 cups a day) or tea (1-2 cups a day) reduced dementia risk, slowed cognitive decline, and preserved cognitive function. Their results are published in JAMA.
“When searching for possible dementia prevention tools, we thought something as prevalent as coffee may be a promising dietary intervention – and our unique access to high quality data through studies that has been going on for more than 40 years allowed us to follow through on that idea,” said senior author Daniel Wang, MD, ScD, associate scientist with the Channing Division of Network Medicine in the Mass General Brigham Department of Medicine and assistant professor at Harvard Medical School. Wang is also an assistant professor in the Department of Nutrition at Harvard Chan School and an associate member at the Broad Institute. “While our results are encouraging, it’s important to remember that the effect size is small and there are lots of important ways to protect cognitive function as we age. Our study suggests that caffeinated coffee or tea consumption can be one piece of that puzzle.”
Early prevention is especially crucial for dementia, since current treatments are limited and typically offer only modest benefit once symptoms appear. Focus on prevention has led researchers to investigate the influences of lifestyle factors like diet on dementia development.
Coffee and tea contain bioactive ingredients like polyphenols and caffeine, which have emerged as possible neuroprotective factors that reduce inflammation and cellular damage while protecting against cognitive decline. Though promising, findings about the relationship between coffee and dementia have been inconsistent, as studies have had limited follow-up and insufficient detail to capture long-term intake patterns, differences by beverage type, or the full continuum of outcomes—from early subjective cognitive decline to clinically diagnosed dementia.
Data from the NHS and HPFS help to overcome these challenges. Participants repeated assessments of diet, dementia, subjective cognitive decline, and objective cognitive function and were followed for up to 43 years. Researchers compared how caffeinated coffee, tea, and decaffeinated coffee influenced dementia risk and cognitive health of each participant.
Of the more than 130 000 participants, 11 033 developed dementia. Both male and female participants with the highest intake of caffeinated coffee had an 18% lower risk of dementia compared with those who reported little or no caffeinated coffee consumption. Caffeinated coffee drinkers also had lower prevalence of subjective cognitive decline (7.8% versus 9.5%). By some measurements, those who drank caffeinated coffee also showed better performance on objective tests of overall cognitive function.
Higher tea intake showed similar results, while decaffeinated coffee did not – suggesting that caffeine may be the active factor producing these neuroprotective results, though further research is needed to validate the responsible factors and mechanisms.
The cognitive benefits were most pronounced in participants who consumed 2–3 cups of caffeinated coffee or 1–2 cups of tea daily. Contrary to several previous studies, higher caffeine intake did not yield negative effects – instead, it provided similar neuroprotective benefits to the optimal dosage.
“We also compared people with different genetic predispositions to developing dementia and saw the same results – meaning coffee or caffeine is likely equally beneficial for people with high and low genetic risk of developing dementia,” said lead author Yu Zhang, MBBS, MS, PhD student at Harvard Chan School and a research trainee at Mass General Brigham.
Trauma patients urgently requiring a breathing tube are more likely to survive if the tube is inserted before arriving at hospital compared to insertion afterwards, suggests a modelling study led by researchers at University College London and the Severn Major Trauma Network.
The researchers found that prehospital emergency intubation of high-risk trauma patients could improve 30-day survival by 10.3%, and could save 170 lives each year in the UK.
The findings of the new artificial intelligence (AI)-supported analysis, published in The Lancet Respiratory Medicine, provide\s the strongest evidence yet that prehospital emergency anaesthesia with intubation saves lives when delivered to those who need it most.
Trauma is a leading cause of death worldwide, with rates in South Africa 5–9 times higher than the global average. But there is a lack of high-quality evidence on the best time to start certain types of care for major trauma patients, such as the insertion of breathing tubes.
Prehospital intubation needs to be administered by an advanced critical care team, specially trained and equipped to administer the anaesthesia required to facilitate the insertion of breathing tubes. In the UK, that is currently provided only by the air ambulance services.
The researchers say their findings could inform policy discussions on funding specialist prehospital critical care teams, which could include public funding for air ambulances or funding additional training for ground ambulance teams, so that more high-risk major trauma patients can have breathing tubes inserted before arrival at hospital.
Joint first author Dr Amy Nelson (UCL Queen Square Institute of Neurology and King’s College London) said: “The airway is a top priority in major trauma, but the question of whether we should intubate before hospital arrival is unsettled because we cannot ethically conduct a randomised trial.
“Emergency care decisions made before hospital admission depend on the combination of many measurements taken under pressure. We used these measurements to answer the question in steps: we first built a machine learning model to identify high-risk patients, then we modelled the impact of early intubation in this group, which showed us that prehospital intubation saves lives.”
For the study, researchers analysed data from 6467 trauma patients treated at Southmead Hospital Major Trauma Centre, Bristol.
The researchers used AI-assisted modelling to predict both who would need intubation and who would likely survive – to isolate the impact that intubation had from other factors such as the injury severity. To facilitate their analysis, they developed a new machine learning model, called ‘Intub-8’, which predicted outcomes based on eight routinely collected prehospital measurements.
The researchers found that among high-risk patients who were identified by the model as needing intubation (229 patients), those who received it before arriving at hospital were 10.3% more likely to survive (within a 30-day period) compared with those who did not.
By scaling up their findings relative to national trauma incidence, the researchers estimate that if every trauma patient who needed prehospital intubation was given it, 170 lives could be saved each year in the UK – roughly one life saved every other day.
Additionally, they conducted a cost-effectiveness analysis, finding that cost savings would be in the range of £101 million annually for the UK, due to reduced costs of further care and lives saved.
Professor Parashkev Nachev (UCL Queen Square Institute of Neurology), joint senior author, said: “In medicine, action and inaction are not morally asymmetric. When we cannot have randomised controlled trial evidence for an intervention, we must use the best available alternative: causal inference from real-world data, assisted by artificial intelligence, the only technology with the power to address the complexity of biological systems.”
Associate Professor Julian Thompson, joint senior author and Clinical Director of the Severn Major Trauma Network, said: “Until now, advanced air ambulance services across the world who respond to critically injured patients have struggled to conduct studies that assess the benefit and cost effectiveness of their life-saving interventions. The use of AI in this study has allowed us to analyse existing data in a totally new way. This reveals the huge impact that advanced care provides when delivered before arrival in hospital.
“These findings may have a huge impact on how UK and international health services look after the most severely injured patients in our societies.”
The authors note that the findings are specific to a mixed rural-urban UK setting where highly trained physician-paramedic teams perform all prehospital intubation. The survival benefit may differ in other healthcare systems or national contexts, and further research is needed to examine long-term outcomes and potential complications.
Medical artificial intelligence (AI) is often described as a way to make patient care safer by helping clinicians manage information. A new study by the Icahn School of Medicine at Mount Sinai and collaborators confronts a critical vulnerability: when a medical lie enters the system, can AI pass it on as if it were true?
Analysing more than a million prompts across nine leading language models, the researchers found that these systems can repeat false medical claims when they appear in realistic hospital notes or social-media health discussions.
The findings, published in the February 9 online issue of The Lancet Digital Health], suggest that current safeguards do not reliably distinguish fact from fabrication once a claim is wrapped in familiar clinical or social-media language.
To test this systematically, the team exposed the models to three types of content: real hospital discharge summaries from the Medical Information Mart for Intensive Care (MIMIC) database with a single fabricated recommendation added; common health myths collected from Reddit; and 300 short clinical scenarios written and validated by physicians. Each case was presented in multiple versions, from neutral wording to emotionally charged or leading phrasing similar to what circulates on social platforms.
In one example, a discharge note falsely advised patients with oesophagitis-related bleeding to “drink cold milk to soothe the symptoms.” Several models accepted the statement rather than flagging it as unsafe. They treated it like ordinary medical guidance.
“Our findings show that current AI systems can treat confident medical language as true by default, even when it’s clearly wrong,” says co-senior and co-corresponding author Eyal Klang, MD, Chief of Generative AI in the Windreich Department of Artificial Intelligence and Human Health at the Icahn School of Medicine at Mount Sinai. “A fabricated recommendation in a discharge note can slip through. It can be repeated as if it were standard care. For these models, what matters is less whether a claim is correct than how it is written.”
The authors say the next step is to treat “can this system pass on a lie?” as a measurable property, using large-scale stress tests and external evidence checks before AI is built into clinical tools.
“Hospitals and developers can use our dataset as a stress test for medical AI,” says physician-scientist and first author Mahmud Omar, MD, who consults with the research team. “Instead of assuming a model is safe, you can measure how often it passes on a lie, and whether that number falls in the next generation.”
“AI has the potential to be a real help for clinicians and patients, offering faster insights and support,” says co-senior and co-corresponding author Girish N. Nadkarni, MD, MPH, Chair of the Windreich Department of Artificial Intelligence and Human Health, Director of the Hasso Plattner Institute for Digital Health, Irene and Dr. Arthur M. Fishberg Professor of Medicine at the Icahn School of Medicine at Mount Sinai, and Chief AI Officer of the Mount Sinai Health System. “But it needs built-in safeguards that check medical claims before they are presented as fact. Our study shows where these systems can still pass on false information, and points to ways we can strengthen them before they are embedded in care.”
The paper is titled “Mapping LLM Susceptibility to Medical Misinformation Across Clinical Notes and Social Media.”
#InsideTheBox is a column by Dr Andy Gray, a pharmaceutical sciences expert at the University of KwaZulu-Natal and Co-Director of the WHO Collaborating Centre on Pharmaceutical Policy and Evidence Based Practice. (Photo: Supplied)
By Andy Gray
In South Africa, as in many places, pharmaceutical companies are not free to change medicine prices as they wish. In his latest Inside The Box column, Dr Andy Gray unpacks how medicines prices are regulated in the country and considers how this regulatory framework might change.
South Africa’s medicine pricing policies are recognised internationally for their commitment to transparency, but the reality may be different from what exists on paper.
Medicine pricing is a good example of the deficiencies in the National Drug Policy (NDP), which has never been revised since it was first issued in 1996. The original policy document proposed the establishment of a Pricing Committee and committed to “total transparency in the pricing structure of pharmaceutical manufacturers, wholesalers, providers of services, such as dispensers of drugs, as well as private clinics and hospitals”.
Two key proposals were that “the wholesale and retail percentage mark-up system will be replaced with a pricing system based on a fixed professional fee” and “price increases will be regulated”. There was also a commitment to monitoring prices in comparison to those charged in other countries. Finally, there was this statement: “Where the State deems that the retail prices of certain pharmaceuticals are unacceptable and that these pharmaceuticals are essential to the well being of any sector of the population, the State will make them available to the private sector at acquisition cost plus the transaction costs involved.”
Few policies survive an encounter with reality, and opposition, and this document is no exception.
Never the twain shall meet
A cardinal feature of South Africa’s medicine pricing system is the clear separation between the public and private sectors.
In the public sector, the prices paid by the provinces, military and prison services are the result of a tender process. Only medicines registered by the South African Health Products Regulatory Authority (SAHPRA) may be offered in response to a tender call. The National Department of Health makes all tenders publicly accessible and also publishes the resultant tender awards, as well as the Master Health Products List, updated whenever any listing changes. The prices paid therefore reflect the downward influence of the buying power of the state. The tenders include a quantification of anticipated demand over the tender period (usually three years). Prices are also influenced by the number of potential suppliers and therefore the extent of competition in the market.
For some critical, high-volume medicines, such as the first-line antiretrovirals, the tender is split among multiple suppliers, at slightly different prices. Split tenders are intended to ensure security of supply if a contracted supplier is unable to meet demand.
Where the state accounts for most of the quantity sold in the country, it is usually able to attract bids at lower prices than are charged in the private sector. However, in some cases, tenders attract no bids and the state is forced to purchase on quotation. Where a registered medicine is only available from a single supplier, the price paid by the state may be closer to that paid in the private sector. In November 2025, the Director-General of Health published a statement of concern about bid prices exceeding the private sector single exit price (SEP), urging manufacturers to “reflect on their pricing practices”.
Although there are some limited agreements to provide state stock, such as childhood vaccines, to private healthcare providers, the two distribution chains and their pricing remain separate. The private sector cannot access medicines at the same price as the state.
Private sector – not entirely transparent
The Medicines and Related Substances Control Amendment Act, 1997, sought to put in place at least some of what was proposed in the 1996 National Drug Policy. After the multinational pharmaceutical industry withdrew a court challenge to the Act in 2001, and after another Amendment Act, the changes came into effect in 2003, but with the pricing portion delayed until 2004. Further delay followed, with court challenges brought by community and hospital pharmacy groups, leading to an eventual Constitutional Court judgment in 2005. While the basic construct remained in place, the government had to revise the dispensing fee.
The basic construct of the pricing provision, which has been inserted into the Medicines and Related Substances Act, 1965, but is not the responsibility of SAHPRA, relies on what is called the SEP. The SEP is defined as “the only price at which manufacturers shall sell medicines and Scheduled substances to any person other than the State”. In other words, the “exit” refers to the price which is charged by the manufacturer to the final seller such as a pharmacy, hospital or healthcare provider. This is a little different from the more commonly used term of a “factory gate price”, which then allows additions to be made at each step in the distribution chain.
The SEP is the price that the final seller charges to the patient or medical scheme. Final sellers are, however, entitled to a dispensing fee, which is set as a maximum each year and differs between pharmacists and licensed dispensing practitioners. Wholesalers do not add a mark-up to the SEP charged by the manufacturer, but are paid a logistics fee by the manufacturer, as a portion of the exit price.
Crucially, the “single” component refers to the intention that the same price would be paid by all buyers, regardless of the volume of medicine procured. In other words, the private sector cannot use its buying power to exert any pressure on manufacturers’ prices. The Act is prescriptive in this regard: “No person shall supply any medicine, medical device or IVD according to a bonus system, rebate system or any other incentive scheme.” While the application of this section to Schedule 0 medicines, medical devices and in vitro diagnostics has been paused, it still applies to other medicines.
Annually, the Pricing Committee asks for input on two elements: the dispensing fees for pharmacists and dispensing practitioners, and the SEP adjustment (SEPA). The latter is a maximum percentage increase that manufacturers can apply to the SEPs on an annual basis. In some years, exceptional additional SEPAs have been allowed, but they have generally mirrored the consumer price index. The SEPA allowed for 2026 was set at a maximum of 1.47%, compared with 5.25% in 2025. The SEPA mechanism has protected South Africa against the large pharmaceutical price increases that have been seen in other countries. However, the initial launch SEP remains unregulated.
The dispensing fees include a flat amount and a percentage of the SEP, varying across 4 price bands. As the price of the medicine increases, the percentage component decreases. For example, the September 2025 version states that where the SEP of a medicine exceeds R1 530.73, the dispensing fee charged by a pharmacist shall not exceed R270.54 + 5% of the SEP.
A spreadsheet showing all declared SEPs (for registered medicines in Schedules 1 to 6) is publicly accessible on the health department’s website. That site also provides access to various SEPA documents. All final sellers are required to disclose to a buyer what the SEP for a medicine is, and then indicate the dispensing fee charged, which cannot exceed the maximum gazetted each year.
So, what’s not transparent?
The first problem lies with the logistics fee paid to wholesalers by manufacturers. Although there is a column in the SEP spreadsheet that shows a logistics fee, the actual amount paid is known to vary considerably. Importantly, where a final seller, such as a large pharmacy chain, owns its own wholesaler, it can gain additional income from the logistics fee. That component is not disclosed to buyers (patients or medical schemes) – but may influence the seller’s ability to charge less than the maximum dispensing fee.
The Act enables the Minister of Health, in consultation with the Pricing Committee, to “prescribe acceptable and prohibited acts” in relation to bonus systems, rebate systems or other incentive schemes. Despite being published for comment on two occasions, in 2014 and in 2017, no final regulations have been issued. The extent to which co-marketing fees, data fees, shelf fees, formulary listing fees, patient assistance programmes, off-invoice rebates and bonus systems have crept back into the private sector is therefore unknown, as is the quantum of such potentially perverse incentives. Certainly, such revenue streams are not transparent to patients and caregivers.
The enforcement capacity of the health department and Pricing Committee is also questionable. South Africa’s much-vaunted transparent medicine pricing system may conceal many unsavoury elements.
New concerns – failure to declare an SEP
Once SAHPRA has registered a new medicine, the online database is updated. However, SAHPRA does not concern itself with pricing. The holder of the certificate of registration (HCR) can choose to sell the medicine only to the state. However, if the HCR wishes to sell the medicine in the private sector, an SEP has to be declared. Some of the questions asked in the declaration form are interesting, but of dubious legal weight. For example, manufacturers are asked: “The methodology used to determine the SEP and factors that influence the price at which the medicine will be sold.” Even though no external reference pricing system is in place, the prices in other countries are requested. While it is reasonable to ask what the registered indications for the medicine are, as approved by SAHPRA, to demand the “prevalence of the disease or condition as established by the applicant in South Africa” is less reasonable. To date, no SEPs have been declared to be “unacceptable”, as was signalled in the NDP in 1996. Manufacturers thus have a relatively free hand to set their private sector launch prices.
However, two high-profile registrations of HIV drugs by SAHPRA, of cabotegravir by GlaxoSmithKline and of lenacapavir by Gilead, have not been followed by the declaration of an SEP. One contributory reason may be a reluctance to make a price to be charged in an upper middle-income country such as South Africa transparent to the rest of world.
Unregistered medicines imported in terms of section 21 (an application to access an unregistered medicine in circumstances where there is no suitable product registered in South Africa) are not subject to the SEP. In the case of the cystic fibrosis treatments sold by the pharmaceutical company Vertex, a refusal to apply for registration by SAHPRA, thus forcing medical schemes and patients to rely on section 21, has allowed the company to reach agreements with specific medical schemes at undisclosed prices. These medicines are not available to public sector patients.
The unknown unknown
Although the National Health Insurance Fund is expected to be an “active purchaser”, using its buying power to exert downward pressure on prices, bolstered by health technology assessment processes, the exact manner in which the prices of medicines will be determined is unclear.
In particular, how the fund will contract with public and private sector providers to serve beneficiaries in a particular geographical area, given the current clear separation in pricing, is yet to be disclosed. Once NHI is fully implemented, the current tender system will not be tenable. A tender award to a single supplier would immediately make all competitors leave the market. Instead, a reimbursement system, perhaps closer to the reference pricing applied in medical scheme formularies, will be needed. The complexity lies in the period of co-existence of the current public and private sectors and a nascent NHI.
Has the NDP 1996 been implemented?
Although a fixed dispensing fee proved impractical, some elements of the 1996 policy are discernible. Regulated price increases are in place, for instance. Other elements are less clearly implemented, and full transparency remains elusive. There is a need to revisit the entirety of the national medicines policy, not least in relation to how best to deliver access to affordable, quality-assured, essential medicines as part of universal health coverage.
*Dr Gray is a Senior Lecturer at the University of KwaZulu-Natal and Co-Director of the WHO Collaborating Centre on Pharmaceutical Policy and Evidence Based Practice. This is part of a series of columns he is writing for Spotlight.
Note: Spotlight aims to deepen public understanding of important health issues by publishing a variety of views on its opinion pages. The views expressed in this article are not necessarily shared by the Spotlight editors.
