Trials In Transfusion Medicine Research Articles

Cluster-randomized trials in transfusion medicine.

Cluster-randomized trials in transfusion medicine.

Inverse probability weighted estimating equations for randomized trials in transfusion medicine

Thrombocytopenia is a condition characterized by extremely low platelet counts, which puts patients at elevated risk of morbidity and mortality because of bleeding. Trials in transfusion medicine are routinely designed to assess the effect of experimental platelet products on patients' platelet counts. In such trials, patients may receive multiple platelet transfusions over a predefined period of treatment, and a response is available from each such administration. The resulting data comprised multiple responses per patient, and although it is natural to want to use this data in testing for treatment effects, naive analyses of the multiple responses can yield biased estimates of the probability of response and associated treatment effects. These biases arise because only subsets of the patients randomized contribute response data on the second and subsequent administrations of therapy and the balance between treatment groups with respect to potential confounding factors is lost. We discuss the design and analysis issues involved in this setting and make recommendations for the design of future platelet transfusion trials.

If we have bandwagons, magic bullets, and theoretical constructs, why do we need randomized clinical trials in transfusion medicine and perioperative hemostasis?

This invited commentary is not so much about science as it is about our lack of knowledge in transfusion medicine and perioperative hemostasis and about how this lack of knowledge affects our practice. As suggested by the title, the intent of this discourse is to be provocative but certainly not contemptuous. Despite widespread collection and administration of red blood cells (81 million units are collected annually worldwide; http://www.who.int/bloodsafety/FactFile2009.pdf), transfusion practice is based on meagre good quality evidence. The most recent search of the Cochrane Database of Systematic Reviews identified a mere 17 trials involving 3,746 patients randomized to interventions based on a clear ‘‘transfusion trigger’’. The authors concluded that restrictive transfusion strategies reduced the risk of receiving a red blood cell (RBC) transfusion and did not appear to impact on the rate of adverse events compared with liberal transfusion strategies. In fact, in the Transfusion Requirements in Critical Care trial, a restrictive transfusion strategy was associated with improved survival in younger and less severely ill patients. Based on data from retrospective cohort studies of patients who refuse transfusions for religious reasons, we all recognize that there is a point where anemia will definitely increase morbidity and mortality. However, the point at which anemia becomes problematic for a given patient is unknown, as is the point at which transfusions will improve survival. Thus, theoretical arguments based on innumerable retrospective cohort studies have been made either in favour of or against a RBC transfusion, and clinical practice varies accordingly. Given the high degree of uncertainty surrounding the benefits or the risks of transfusions, the decision to transfuse can be relatively difficult in certain cases. When a patient is bleeding during surgery, the hemoglobin (Hb) concentration falls and the patient may require a RBC transfusion depending on his/her physiological condition, the clinical context, and the Hb concentration. However, in the absence of convincing evidence, clinicians tend to rely mainly on the Hb concentration when deciding whether to transfuse patients, irrespective of the patient’s age and physiological (particularly cardiovascular) condition. This oversimplification of a complex situation is probably unavoidable at present, but it underscores the urgent need for trials to test the effects of different transfusion strategies on functional outcomes, morbidity, and mortality in different patient populations. In recent years, only three studies have presented high quality evidence regarding the Hb concentration that should prompt consideration of transfusion, and a fourth should be published soon. The latter study should provide helpful information Dr. Hardy holds the Hema-Quebec Foundation—Bayer Chair of Transfusion Medicine of the University of Montreal.

The relevance of practice misalignments to trials in transfusion medicine

Practice misalignments can occur in any clinical trial investigating a pre-existing therapy that is typically adjusted based on clinical characteristics outside of the trial setting. To eliminate the heterogeneity in clinical practice, recent trials investigating titrated therapies have randomized patients to fixed-dose regimens without including a routine care control group receiving titrated therapy. In these trials, the normal relationships between clinically important characteristics and therapy titration are disrupted. Within each arm of the trial, randomization creates subgroups of patients receiving levels of therapy inconsistent with current practices outside of the trial. These practice misalignments may have outcomes worse than routine care and may compromise patient safety. In addition, comparisons of trial arms with practice misalignments have limited interpretability and generalizability. In this review, we use examples from the literature to discuss how practice misalignments can impact the safety, results and conclusions of clinical trials. In addition, we discuss methods to characterize relationships between therapy titration and clinical characteristics and trial design strategies that may minimize practice misalignments.

Pilot trials in transfusion medicine

Preparatory work for clinical research in transfusionmedicinetakesonmanyforms.Background research activity which informs a future study is referred to as pilot work. Preliminary research projects of various designs with a specific hypothesis, objective, and method are referred to as pilot studies. Small-scale randomized controlled trials (RCTs) with specific feasibility or scientific objectives designed with a future large RCT in mind are pilot trials. 1 In this report, we

The top ten list of randomized controlled trials in transfusion medicine.

The top ten list of randomized controlled trials in transfusion medicine.

The clinical consequences of the red cell storage lesion.

W E ARE NOW ENTERING the second century in which human blood has been stored for transfusion. In the last 2 decades of the last century, we witnessed a dramatic shift ''1 in which a product once regarded as one of the great advances in modern medicine ''2 was now viewed as potentially harmful. Precipitated by the identification of transfusion-transmitted infections, this paradigm shift has led to a reexamination of the quality of stored blood for transfusion. In this context, contaminating leukocytes, which were an accepted part of red blood cell (RBC) transfusion, have now been implicated in alloimmunization, graft-versus-host disease, cytomegalovirus transmission, and immunomodulation. 3 Another recognized biologic phenomena associated with RBC storage includes the induction of the storage lesion, which can be defined as a series of biochemical and biomechanical changes in the red cell occurring during preservation that reduces subsequent in vivo survival and function. Our understanding of the mechanisms involved in these changes is incomplete, but recent clinical trials and animal experiments have raised fundamental questions about the putative efficacy of stored blood. A large randomized trial comparing a liberal with a conservative transfusion strategy in the critically ill yielded the surprising result that lowering the hemoglobin threshold for RBC transfusions is not only safe but may be associated with reduced mortality. 4 Two studies have suggested that morbidity or mortality may increase with the duration of RBC storage before transfusion. 5,6 In light of these recent findings, we reexamine storage-related changes in RBC shape in relation to posttransfusion survival and RBC function. The experimental data from animal models will be discussed along with recent clinical trials in transfusion medicine, speculating on a possible association between storage-related changes and adverse clinical consequences of transfusing blood.

Multicenter randomized controlled trials in transfusion medicine

Multicenter randomized controlled trials in transfusion medicine