Differential pricing of drugs: a role for cost-effectiveness analysis?

Internationally, the high costs of pharmaceutical products limit access to treatment. The principle of differential pricing is that drug prices should vary according to some measure of affordability. How differential prices should be determined is, however, unclear. Here we describe a method whereby differential prices for essential drugs could be derived in countries of variable national wealth, and, using angiotensin-converting enzyme inhibitors provide an example of how the process might work. Indicative prices for drugs can be derived by cost-effectiveness analysis that incorporates a measure of national wealth. Such prices could be used internationally as a basis of differential price negotiations.     

Will immunotherapy lead to a breakthrough in the treatment of older adults with ALL?

Historically, older adults with B-cell acute lymphoblastic leukemia (ALL) have done poorly with chemotherapy-based treatment. Therefore, new innovative approaches are urgently needed to improve outcomes for this population. CD19-targeted immunotherapies such as blinatumomab and chimeric antigen receptor (CAR) T cell therapy have produced remarkable responses in relapsed/refractory (r/r) B-cell ALL, including clearance of minimal residual disease (MRD). Available data support the efficacy and safety of blinatumomab in older adults with advanced B-cell ALL. Therefore, its application is being extended to frontline regimens for B-cell ALL, particularly in older adults. There are several studies actively examining the role of blinatumomab alone or in combination with attenuated dosing of conventional chemotherapy or novel agents in older adults with newly diagnosed ALL and early data are encouraging. While CD19-targeted CAR (CD19CAR) T cell therapy is active in children and young adults with r/r B-cell ALL, data supporting its efficacy and safety in older adults with ALL is scarce. Furthermore, the commercially FDA approved CD19CAR T cell therapy product for r/r ALL is restricted only to patients ≤25 years of age. Although there are concerns about older adults tolerating the expected toxicities associated with CAR T cell therapy, which may be life threatening, tailored approaches for prophylactic and pre-emptive interventions combined with utilization of safer CAR T cell platforms may improve tolerability and further extend the use of this promising treatment to older patients with ALL. In this review, we will discuss the progress in immunotherapies for older adults with B-cell ALL and their potential for transforming frontline therapy for newly diagnosed patients.     

Can treatment of P. vivax lead to a unexpected appearance of falciparum malaria?

Of 994 patients admitted to the Bangkok Hospital for Tropical Diseases for P. vivax malaria, 104 (10.5%) experienced appearance of Plasmodiumfalciparum following drug treatment for P. vivax . In all patients, P. falciparum parasites were not found by microscopic examination upon admission. The mean time for P. falciparum appearance was 12.6 days after the commencement of chloroquine treatment. Patients experiencing appearance of P. falciparum had significantly lower hematocrit, and greater initial P. vivax parasite counts. We use a mathematical model to explore the consequences of chloroquine treatment of such mixed infections. Both clinical results and features of the model suggest that such "hidden infections" may be quite common, and that the appearance of P. falciparum may be stimulated by treatment of P. vivax.     

Can guidelines for the treatment of respiratory infections lead to reduced rates of antibiotic resistance?

Guidelines have been developed for the therapy of both community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP), and, potentially, if applied appropriately, could lead to a containment or reduction in the frequency of antibiotic resistance. In the therapy of CAP, guidelines could minimize the use of excessive antibiotic therapy, and if they also improve the accuracy of therapy, they could minimize the emergence of resistant organisms in the community. However, the impact of such guidelines on resistance remains to be shown. In the near future, CAP guidelines could help contain the growing problem of quinolone-resistant pneumococci by advocating the use of the most effective of the new agents, administered at the optimal dosages. When managing HAP, the use of guidelines could improve outcome by leading to a greater percentage of patients receiving adequate empiric antibiotic therapy. It remains uncertain whether such an approach can minimize the emergence of antibiotic resistance, particularly in the intensive care unit (ICU), but it is clear that if guidelines are to be accurate, they must account for the resistance patterns that are unique to each individual hospital setting. To date, the use of computer-assisted guidelines for the therapy of nosocomial infections has been successful in minimizing the frequency of inadequate therapy, with no negative impact on antibiotic resistance. Antibiotic restriction policies have been proposed as a way to have an impact on resistance, with variable effects. In the future, antibiotic rotation is likely to be studied as a way to reduce resistance, particularly in the ICU, but a number of practical issues may limit the efficacy of such an approach.     

Duration of treatment in postmenopausal osteoporosis: how long to treat and what are the consequences of cessation of treatment?

Although a variety of medications are effective for the treatment of postmenopausal osteoporosis, there is concern that long-term use may incur side effects. Consequently, some have proposed discontinuing or temporarily suspending treatment after a defined period of time. As the benefits of fracture risk reduction may recede during this "drug holiday", the clinician may be faced with deciding when to resume therapy (and with which agent) while avoiding the possible cumulative risk of side effects. This article summarizes data regarding length of treatment and the effects of cessation of treatment on bone density, bone turnover markers, and fracture risk.     

Is time to joint replacement a valid outcome measure in clinical trials of drugs for osteoarthritis?

Each of the five sets of criteria for THA mentioned in this article should be regarded as preliminary. They require validation in future studies conducted in various cohorts of patients and in different countries. Moreover, a set of generally accepted criteria is badly needed. The number of proposed sets of criteria listed in this article indicates clearly that no consensus presently exists with respect to the optimal time for a patient who has hip OA to undergo THA.     

How to guide therapeutic decisions in a patient-tailored approach to treatment of IBD?

Therapeutic decisions in the treatment of IBD involve the initial choice of therapy(ies) and designing a long-term strategy for the individual patient. Putting forward clear therapeutic aims is therefore critical in order to assess treatment success and to guide the sequential use of therapies. Although the ultimate goal of therapy is to achieve steroid-free remission and avoid complications and surgeries, the first therapeutic intervention will achieve these aims only in a minority of patients. Depending on the requirements and successes of each stage of therapy, interim goals are pursued which may be small steps towards the total control of the disease. A patient-tailored approach does not necessarily conflict with algorithm-based decision-making; indeed, they are complementary. The former allows the skipping of some steps in the algorithm, based on the individual patient characteristics. The latter supplies a basis for the rational sequential use of drugs. Many physicians use an accelerated step-up approach in the treatment of IBD, although it has not yet been established whether this is associated with a better outcome. Whether or not an endoscopic or (and) CT or MRI assessment is conducted, the therapeutic approach should be based on mucosal activity and the location and extent of the disease. Treatments that do not heal (or at least improve) ulcers are not to be continued if they have been given a reasonable time to work. Biomarkers like C-reactive protein and calprotectin can be useful surrogates in this setting.     

Does enrollment in a randomized clinical trial lead to a higher cost of routine care?

Background Reimbursement for the routine care of patients enrolled in clinical trials is controversial. Our objective was to determine the added medical costs, if any, associated with enrollment in a randomized clinical trial. Methods We analyzed data from the Myocardial Infarction Triage and Intervention (MITI) Trial (1988-1991) and the registry of all patients admitted to 19 Seattle area coronary care units (1988-1993). The major trial entry criteria were age 35 to 71 years, symptom duration 15 minutes to 6 hours, and acute myocardial infarction on electrocardiogram. The trial group consisted of 264 of 324 randomized patients who received thrombolytics and had available cost data. From 11,932 registry patients, we identified a control group who met trial entry criteria but who were not enrolled because of logistic barriers or presentation outside the trial enrollment period, 335 of whom received thrombolytics and had available cost data. The groups were compared for total cost for initial hospitalization, with and without multivariable adjustment for baseline characteristics. Results Total hospital cost was not different between trial patients (median $11,516) and control subjects (median $14,200) (trial/control mean cost ratio 0.91 [95% CI 0.82-1.02]). Participation in the trial had an insignificant effect on costs in the multivariable model (cost ratio 1.04, 95% CI 0.95-1.16). Significant predictors of cost included hospital of admission, length of stay, and coronary revascularization procedures. Conclusion Participation in the MITI randomized trial had no effect on the cost of routine care. (Am Heart J 2002; 143:140-4.)     

Hypertension in pregnancy: is it time for a new approach to treatment?

Hypertensive disorders represent major causes of pregnancy-related maternal mortality worldwide. The current definition and treatment recommendations for elevated blood pressure (BP) during pregnancy in the United States have remained unchanged for many years, unlike the recommendations for hypertension treatment in the general population. Clinical studies have provided convincing evidence that women with hypertensive pregnancy disorders are at both immediate and long-term risk for cardiovascular complications; these findings suggest that consideration be given to lowering the presently recommended BP thresholds, both for the initiation of therapy and for therapeutic targets, and to simplifying the approach to the management of elevated BP in pregnancy. This review focuses on the current treatment strategies for hypertensive pregnancy disorders, new developments in the field of hypertension, in general, and in pregnant patients, in particular, and their potential impact on contemporary BP goals and the use of specific antihypertensive medications in pregnancy.     

Nursing homes: a suitable alternative to hospital care for older people in the UK?

Over the past two decades nursing homes have become the major supplier of long-stay care for frail older people in the UK. Demographic projections indicate that the volume of nursing home places will continue to increase to keep pace with demand and that the population of homes will become steadily more dependent. Little systematic research exists to indicate how nursing home care compares with hospital care; the evidence that does exists tends to be restricted to local studies and thus is not generalizable. Local studies indicate that in both care settings there are shortfalls in terms of meeting basic quality of care standards. Despite this, there is obvious potential for nursing homes to act as an alternative to hospitalization, provided that there is suitable access for residents to specialist care and, for example, appropriate administration of medicines. Proposed changes in government policy will introduce more uniform standards in nursing homes and associated inspection structures and procedures. However, further research is needed to ascertain the clinical and consumer value of different interventions in nursing homes, and the cost-benefit of enhancing provision available in terms of preventing or forestalling demand on hospitals or reducing hospital length of stay. In the light of the commitment to develop evidence based practice, it is important that such research is urgently advanced to eliminate poor practice. In our rights conscious society, future generations of older people are unlikely to be as tolerant of substandard care.