By Peter Schueler, MD, Sr VP drug development solutions, neurosciences at ICON plc.
The International Traumatic Brain Injury Research (InTBIR) initiative was established in 2011 to facilitate global research in the field of traumatic brain injury (TBI), the neurological disorder with the highest incidence levels.
In 2017, a first report about the status of research was published by the Lancet Neurology Commission (ref.1). At the end of 2022 a follow-up report was issued (ref.2)and revealed several new and somewhat unexpected facts about TBI.
The reports and findings are based on data from a number of large-sized TBI registries. These include Center-TBI, which initially was a European initiative and launched in 2014.
It later evolved to a global project with links to similar databases in Australia, China and India. That offered the opportunity to compare TBI in high- and low-income regions.
Center-TBI is currently also closely collaborating with its US equivalent called Track-TBI.
Combined, these prospective datasets with intense data sampling represent over 22,000 TBI patients’ data (China Center-TBI: 13,138; EU Center-TBI: 4,388; Track TBI US: 2,537; OzENTER Australia 2,336).
Nearly, the same number of patients, 21,681, are documented in a Center TBI registry, albeit this is less data rich.
As one of the co-authors of the reports published by the Lancet Neurology Commission, in this article, I will share some of the significant findings that have been identified. These include:
TBI is not a disease of young men (playing football or driving motorcycles)
In line with demographics, most hospital admissions for TBI occur in people over the age of 65, followed by children and adolescents. 56 per centof TBIs in Center TBI are caused by falls, typically (71 per cent) experiencing a low energy (ground level) fall at a median age of 74 years.
The degree of frailty, and not the age per se, was significantly associated with unfavourable outcomes.
Nonetheless, patients injured by low-energy falls are about 50 per cent less likely to receive critical care or emergency interventions, compared with those injured by high-energy mechanisms, such as road traffic incidents.
This may be due to the fact their risk may get underestimated based on initial Glasgow Come Scale grading. Most clinical trials in TBI still exclude this relevant population.
Sports activities caused 8.7 per cent (US) and 7 per cent (EU) respectively of all documented TBIs
In the EU, the riskiest activities were horse-riding (accounting for 19 per cent of those 7 per cent), skiing (16 per cent), cycling (11 per cent) and soccer (11 per cent).
Violence and crime are still significant causes of TBI
This equally applies to US and EU, with 6.7 per cent of all civilian causes. Intimate partner violence most often affects women (75 per cent) and results in severe TBI.
Biomarkers can improve access to required intensive care
Computer Tomography (CT) is currently the method of choice to identify structural damage in TBI. Even though clinical decision rules the triage of CT scans to those requiring it, the process is still most inefficient, with over 90 per cent of all CT scans for TBI not showing intracranial injury.
Blood biomarkers such as GFAP (glial fibrillary acidic protein) and UCH-L1 (ubiquitin carboxy-terminal hydrolase L1) can better rule out the need for a CT and are now available as plasma tandem tests in the US and EU.
These markers also improve the precision of prognostic models such as CRASH (ref.3) and IMPACT (ref.4), potentially allowing for a more personalised treatment in the future.
Severe TBI is a systemic disease
55 per cent of TBI admissions to intensive care also have extracranial involvement (35 per cent thorax, 18 per cent spine, 17 per cent extremities, 12 per cent kidney). Unsurprisingly, these are typically associated with worse outcomes for the patient.
There is still substantial variation in pre-and hospital care
The good news is that such inconsistencies did not always translate into different outcomes, but clinicians often use more hazardous therapies before exhausting safer options.
As an example, decompressive craniectomy was performed as a primary procedure in 1,354 (48 per cent) of 2,804 patients with severe TBI in the China Centre registry, and in 222 (20·8 per cent) of 1,068 patients in Center-TBI. This is in spite of the fact that no evidence is yet available to support the use of decompressive craniectomy as a primary procedure.
Outcome in mild TBI is also impacted by pre-injury status
Other than in the models CRASH and IMPACT for moderate to severe TBI (see above), data for mild TBI showed that in addition to injury severity, pre-injury health and sociodemographic characteristics (e.g. education, employment, sex, race and ethnicity) are also prominent predictors of outcome.
However, this is not yet operationalised in a predictive model, despite over 90 per cent of the cases presenting to hospital as mild i.e. with a Glasgow Coma Score of between 13 and 15.
TBI is an under-served chronic disease
Only 10 per cent of centers in the Center-TBI registry routinely schedule a follow-up appointment for patients who are discharged with TBI.
At 6 months after moderate to severe injury, 90 per cent of documented patients in Center TBI reported rehabilitation needs, but only 30 per cent received in-patient rehabilitation, while 15 per cent received out-patient rehabilitation. The situation in low-income and developing regions was worse.
In India, for example, only 0.4 per centof patients were discharged to a rehab facility. Even with mild TBI, about 50 per cent of patients did not recover to pre-TBI levels of health by 6 months after their injury.
Conclusions
This latest report shows that there is still much to learn about the causes, prevalence and treatments of TBI.
What is clear is that well-designed registries are hugely important.
It is through structured prospective collection of data across the full time-course of a disease that will reveal the gaps in medical care and allow for the most efficient allocation of limited healthcare resources.
Performing such research in low-income countries as well is a crucial contribution to improved healthcare, globally.
References
- Maas AIR et al, Lancet Neurol 16 (2017): 987-1048.
- Maas AIR et al, Lancet Neurol 21 (2022): 1004–60
- Perel P et al, BMJ 336 (2008): 425-429
- Steyerberg EW et al, PLoS Med 5 (2008): e165
Peter Schueler MD is board certified in neurology and in pharmaceutical medicine (Swiss Medical Association). After his medical education he worked in the pharma industry, and since 2000, has worked in the CRO world, being with ICON since 2007. He has issued over 40 publications as first author on drug development and drug safety. In 2015, his book, Re-engineering clinical trials, was published by Elsevier. He continues to lecture in pharmaceutical medicine at the University of Duisburg- Essen, Germany, and at the European Center Pharmaceutical Medicine (ECPM), Basel, Switzerland.
