Every practitioner strives to provide the best possible treatment to their patients. The optimal goal would be to cure the disease if possible, or at least to stop it without inducing side effects. Evidence-based recommendations are readily used to assess different therapeutic regimens. But what does evidence mean anyway – especially in everyday clinical practice?
The buzzword “evidence” conveys a certain degree of confidence in medicine. Recommendations made on this basis are not based solely on theories or expert opinion, but on scientific evidence. The aim is to generate reliable answers regarding optimal treatment management in the respective indication. Accordingly, the evidence pyramid was used early on to categorize the different sources (Fig. 1) [1]. Different versions of the evidence pyramid have been described. But all focused on using weaker study designs as a base (basic science and case series), followed by case-control and cohort studies in the middle, then randomized controlled trials (RCTs), and systematic reviews and meta-analyses at the top. In principle, this may well be correct. Nevertheless, even clinical studies are not free of errors. Typical biases are, for example, in execution, evaluation, or reporting. However, patient selection, treatment plan, and treatment setting may also determine the extent to which study results can be generalized.
There is always a debate about how valid data from clinical trials can actually be. A recent review showed that of 1640 studies analyzed that provided information on bias risk, 1013 (62%) were associated with high bias risk (poor), 494 (30%) were unclear, and only 133 (8%) were associated with low bias risk [2]. Back in 1994, Doug Altman opined, “We need less research, better research, and research that is done for the right reasons.” But what does that mean in terms of implementation?
Evidence does not necessarily mean well studied
Taking studies in the field of schizophrenia, for example, a meta-analysis regarding the efficacy of long-acting injectable (LAI) vs. oral antipsychotics with respect to relapse prevention in maintenance therapy showed that there were no significant differences [3]. At least not when analyzing randomized clinical trials (RCTs). If, on the other hand, cohort studies and pre-post studies are also included in the analysis, a significant superiority of LAI over oral administration is shown [4]. However, what has also been underlined is the fact that patients in randomized clinical trials are usually very adherent and do not always match the clients in everyday treatment [3].
Are real-world studies the better evidence base?
Real-world evidence (RWE) is therefore becoming increasingly important. It corresponds to clinical evidence regarding the benefits, advantages, and risks of a drug obtained via real-world data (RWD). These are often generated via registry studies, non-interventional studies, case reports, and practice experience reports. The advantage of RWD: the real patient population is represented. Many patients with comorbidities and comedications are not enrolled in clinical trials, even though they may play a significant role in clinical practice. Therefore, the results are not necessarily directly transferable to everyday care. RWE closes this gap. Real-world studies are therefore becoming increasingly important and are also being carried out more frequently. Currently, a 13-week non-interventional, prospective, multicenter study (ACTIVATE) is being acquired to evaluate the efficacy and tolerability profile of brexpiprazole in adult schizophrenia patients to be treated as outpatients. The aim is to use the newly gained knowledge to make treatment management more patient-centered – taking into account the reality of life in Switzerland.
Congress: FomF Update Refresher
Literature:
- Murad, et al: New evidence pyramid. Evid Based Med 2016; 21: 125-127.
- Pirosca, et al: Tolerating bad health research: the continuing scandal. Trials 2022; 23: 458.
- Kishimoto, et al: Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: A meta-analysis of randomized trials. Schizophrenia Bulletin 2014; 192-213.
- Kishimoto, et al: Long-acting injectable versus oral antipsychotics for the maintenance treatment of schizophrenia: a systematic review and comparative meta-analysis of randomised, cohort and pre-post studies. Lancet Psychiatry 2021; 8(5): 387-404.
InFo NEUROLOGY & PSYCHIATRY 2022; 20(5): 24.
