If you are involved in clinical trials for gastrointestinal diseases, it is essential to understand that achieving optimal treatment results can be difficult. Fortunately, there are several strategies you can implement that can help you achieve the best possible outcomes. For example, you can restrict the number of patients you are treating or use restrictive transfusion techniques.
Restrictive transfusion strategy
A restrictive transfusion strategy is more effective and safer than a liberal one in gastrointestinal clinical trial management. Compared to a liberal system, which requires a target hemoglobin (Hb) level of at least 9 g per deciliter, the restrictive approach reduces the Hb concentration by approximately 1.48 g/dL. Moreover, it effectively improves survival rates in patients with severe upper gastrointestinal bleeding. A restrictive transfusion strategy may offer medical benefits to sicker, older patients but is only sometimes valuable for most patients. It is only preferred if evidence suggests it is superior to the liberal transfusion strategy. In addition, it is essential to remember that a restrictive transfusion strategy can also be detrimental to some patients. Thus, an adequately powered trial is needed to determine whether this effect occurs in the general population. Another limitation is transfusion triggers in RCTs, which do not control for normovolemia. The restrictive transfusion strategy also shows some promise in hip fracture surgery. However, there is insufficient evidence to make a specific recommendation for this population.
Communication with patients and clinicians
Delayed release DMF, an oral disease-modifying treatment for RRMS, is associated with an increased risk of gastrointestinal adverse events (AEs). Most AEs reported in clinical trials were related to delayed release DMF. These events can hinder symptomatic management and result in the discontinuation of therapy. Therefore, it is essential to understand how to communicate with patients and clinicians about delayed-release DMF AEs. A survey of investigators experienced in delayed-release DMF was conducted to obtain guidance for clinicians. In addition to gaining insight into the incidence and severity of AEs, information was obtained on strategies for symptom management. Investigators responded to a retrospective questionnaire containing open-ended and closed-ended questions. Investigators were asked to evaluate each AE’s severity and the degree to which the symptom interfered with daily activities. Approximately one-third of participants experienced an AE, the most common being abdominal pain. Some participants also experienced vomiting and diarrhea. Most AEs were classified as moderate and mild. The frequency and severity of AEs decreased with time. Patients reported an overall average GI symptom severity of 4.1. The highest occurrences of flushing occurred during the first month of exposure. During the second and third months, the incidence of GI tolerability decreased. An estimated 4% of study participants discontinued the treatment because of GI AEs. Several strategies for symptom management were implemented, including interruption of therapy, symptomatic therapies, and dose reduction. However, some AEs are more severe than others, which can lead to a decreased quality of life.
Investigators participating in the delayed-release DMF clinical trial agreed that patient education was critical before treatment. They recommended that patients be educated about the risk of GI AEs and the appropriate management strategies. Moreover, investigators identified the importance of avoiding gastrointestinal medications and taking medication with food. Despite the potential for bias, these investigators’ opinions on AE management were based on their experiences during double-blind phase 3 trials. Although not rigorously tested, they reflected the experience of delayed-release DMF users.
Simplification is key
Simplification is an essential step in the management of gastrointestinal clinical trials. While simplification has many benefits, it is necessary to make sure that the information value of a model is recovered. Using a systematic method can help with this.
Several different approaches to model simplification exist. Some of them are based on qualitative and quantitative modeling. These methods mainly focus on identifying significant system elements, such as node importance or multi-output and multi-input variables. Others concentrate on encapsulation procedures or reduction. Regardless of the type of method used, it is essential to assess the procedure’s suitability and how well it can be applied. It is also necessary to consider the limitations of the method. One method is based on encapsulation procedures and involves removing inputs and outputs. Another is based on reduction, which suppresses in-degree and betweenness variables. In both cases, there were no corresponding records in the Scopus database. A third method is based on the centrality theory, a formal model simplification approach. The process is iterative. Meaning steps are repeated if the model meets specific criteria. However, it is associated with the loss of model structure.
The original systematic method of simplification is a routine procedure based on three activities. These include encapsulation, order-oriented reduction, and endogenization. Each of these steps has its limitations. For example, the simplification process could be interrupted before all the steps are completed. Nevertheless, the original method can be applied in practice. Moreover, it opens up new research directions.
