Zainab’s eldest son, aged six, uses his carefully constructed Lego to ‘photograph’ his mother in their living room. Shortly after giving birth to him, Zainab haemorrhaged, and on the advice of a doctor at University College Hospital, she agreed to take tranexamic acid. Zainab is convinced that the drug saved her life. Etinosa Yvonne © Wellcome Trust

Zainab lives in Ibadan, Nigeria. When she went into labour seven years ago, she decided to go to UCH, where she worked as a health attendant. She felt perfectly well, but it was her first child, so she didn’t know what to expect and didn’t want to take any risks. Her husband was at work, but she didn’t ask him to go with her. She walked into the hospital herself and presented at the labour ward.

At first, things went smoothly. Her child was delivered, a healthy baby boy. After that point, her memory is hazy.

“I can’t even explain, the music changed within two seconds. I knew I had a baby boy, but the only thing I can remember is opening my eyes and seeing I was in an anti-shock gown.” These compression garments are sometimes used to stem bleeding.

Zainab remembers a doctor explaining to her that a trial was going on, and that there was an injection that might stop the bleeding. She agreed to have it. She was absolutely sure that she was going to die. The doctors administered tranexamic acid along with a blood transfusion. She doesn’t know how long it took, but the bleeding stopped.

“I thank god that research was going on there,” she says. “In short, I am alive. My baby is doing fine. Without that research, I might not be alive today.”

Although she was careful about her health and sought medical support during her pregnancy, Zainab had never heard of postpartum haemorrhage.

“I knew women were dying in delivery, I knew things happened, but I thought I could never be a victim.” In May, her son will be seven. She often thinks about the trial. “If this drug was not available, where would I be today? Who would be taking care of that poor boy?”

In fact, now that the trial is over, tranexamic acid is not available in much of Nigeria, or in many other countries where maternal mortality is high. Nigeria’s health minister Isaac Adewole, a gynaecologist by training, issued a directive recommending that every hospital in the country stock it. But progress has been slow, in the face of underfunding and poor infrastructure.

“The drug is available, but not as widely available as we would wish,” says Bukola Fawole, the country’s WOMAN project lead. “We want it to be available in every nook and cranny.” He and his colleagues have been running sessions with gynaecologists, obstetricians and midwives to raise awareness of the drug. These efforts are ongoing, but the problem of distribution remains. Tranexamic acid is not produced in Nigeria.

The price increased after the trial results – perhaps because of increased demand, as well as a simultaneous collapse in the Nigerian currency. During the trial, the drug was provided for free to the 50 hospitals that took part. Today, even those hospitals do not all stock tranexamic acid, because of the cost and the difficulty of finding a reliable supplier.

According to Tolulope Adebisi, the pharmacist at UCH in Ibadan, it can be challenging to get hold of tranexamic acid. Hospital pharmacies work privately, on a supply-and-demand basis. If a doctor doesn’t prescribe a drug, pharmacists won’t stock it, but this can become a vicious circle, as doctors won’t prescribe drugs that are not routinely stocked.

“Drug companies don’t want to tie up their capital with drugs like that, except if they are sure of a ready market,” says Adebisi. “They prefer antibiotics, antimalarials, things that are fast-moving.”

A woman stands in front of a counter in the pharmacy at University College Hospital, Ibadan, as she waits to collect the drugs she purchased. Etinosa Yvonne © Wellcome Trust

At a large teaching hospital such as UCH, pharmacists have well-developed relationships with a range of suppliers, and are more easily able to stock tranexamic acid.

“We have our regular reliable suppliers,” she says. “For smaller hospitals, it might be more difficult to access.” A vial of 500 mg of tranexamic acid can cost 1,500 naira (£3.20), and two would be needed for the recommended dose. This is significantly more expensive than the other drug treatments for postpartum haemorrhage – a further deterrent for patients. According to Adebise, some cheaper versions of the drug are becoming available, but they are still not widely accessible.

This is all the more frustrating, because where tranexamic acid is being used, it appears to be having an effect.

“We still encounter postpartum haemorrhage a lot, it is still very common, but they don’t die,” says Oladapo Olayemi, one of the consultants at UCH. “Locally here, the hospital has adopted it, and the impact was immediate.” He notes a general improvement in maternal outcomes alongside the impact of tranexamic acid – with traditional midwives, for instance, being faster to refer women to hospital when they are experiencing haemorrhage.

Maternal mortality remains high in certain countries for a complex host of reasons going far beyond the actual medical complications – from poor nutrition to the marginalisation of women.

In much the same way, the challenges in implementing new treatments are multifaceted. Studies suggest that there is typically a time lag of 17 years between a successful clinical trial result and a drug being widely in use around the world. The reasons for this can vary. It takes time to change human behaviour, and for doctors to integrate a new treatment into their arsenal. Drug supply can also be an issue. And in countries such as Pakistan and Nigeria, where state infrastructure is weak, implementation of recommendations can be slow.

In some countries that took part in the trial, such as Uganda, tranexamic acid is barely being used.

“The infrastructure is just not there in some places,” says Ian Roberts, one of the trial directors at the London School of Hygiene and Tropical Medicine.

This problem is not unique to tranexamic acid. Creating a market for a new drug, or for a new use of an old drug, is a laborious and unglamorous process. In international development parlance, this is referred to as “market shaping”, attempting to create a balance where there is enough demand for a drug to make it profitable for pharmaceutical companies but also good value for the countries purchasing it.

Many doctors have been unaware of what tranexamic acid can do. In Pakistan, faced with so many cases of postpartum haemorrhage and too little use of the drug to treat it, Rizwana Chaudhri decided to take action.

“What is the use, putting in so much effort and money, and it goes on the shelves?” she says. The country has a well-developed pharmaceutical industry, and unlike in Nigeria, several companies produce tranexamic acid domestically, meaning that it is cheap and easily available.

Soon after the trial results, Chaudhri got in contact with one of the largest of these, Hilton Pharmaceutical. In the absence of public funding to disseminate news of the successful results, the company funded Chaudhri and her colleagues to hold seminars around the country to inform clinicians about the new use for tranexamic acid. So far, sessions have been held in Pakistan’s major cities – Islamabad, Karachi, Lahore, Peshawar and Quetta – with plans for more over the next year.

Given its easy availability in the country, the drug was already widely used for a variety of conditions, but if it was used for postpartum haemorrhage, this was ad hoc given the lack of clinical evidence.

“Previously, even if it was practice to give tranexamic acid, it was usually given late – if you tried everything else and that failed,” says Chaudhri. “But this trial has proved that this is first-line management. Everybody who has the knowledge is now using it.”

Tranexamic acid stored in the dispensary at Holy Family Hospital, Rawalpindi. Saiyna Bashir © Wellcome Trust

When it comes to reducing maternal mortality, there are many contributing factors that have nothing to do with the drugs on offer. In both Pakistan and Nigeria, as well as in a host of other lower-income countries, women in rural areas may not have easy access to a proper hospital in which to deliver; if they are referred, there are often no ambulance services to transfer them.

Even if gynaecologists and obstetricians at hospitals know what to do and how to do it, staff at more basic healthcare facilities will still be ill-equipped to treat postpartum haemorrhage.

“We need to train people,” says Chaudhri. “Even if they’re not well-versed with all the procedures, they should know how to transfer the patient, do the packing and give an IV line.”