Ameet Sarpatwari

Effects of eradication of Helicobacter pylori infection in patients with immune thrombocytopenic purpura: a systematic review

Whether the eradication of Helicobacter pylori infection can increase the platelet count in patients with immune thrombocytopenic purpura (ITP) is still a controversial issue. To provide evidence-based guidance, we performed a systematic review of the literature published in English, selecting articles reporting 15 or more total patients. We identified 25 studies including 1555 patients, of whom 696 were evaluable for the effects of H pylori eradication on platelet count. The weighted mean complete response (platelet count > or = 100 x 10(9)/L) and overall response (platelet count > or = 30 x 10(9)/L and at least doubling of the basal count) were 42.7% (95% confidence interval [CI], 31.8%-53.9%) and 50.3% (95% CI, 41.6%-59.0%), respectively. In 222 patients with a baseline platelet count less than 30 x 10(9)/L, the complete response rate was 20.1% (95% CI, 13.5%-26.7%) and the overall response rate was 35.2% (95% CI, 28.0%-42.4%). The response rate tended to be higher in countries with a high background prevalence of H pylori infection and in patients with milder degrees of thrombocytopenia. These findings suggest that the detection and eradication of H pylori infection should be considered in the work-up of patients with seemingly typical ITP.

Thromboembolic events among adult patients with primary immune thrombocytopenia in the United Kingdom General Practice Research Database

Background The risk of thromboembolic events in adults with primary immune thrombocytopenia has been little investigated despite findings of increased susceptibility in other thrombocytopenic autoimmune conditions. The objective of this study was to evaluate the risk of thromboembolic events among adult patients with and without primary immune thrombocytopenia in the UK General Practice Research Database. Design and Methods Using the General Practice Research Database, 1,070 adults (≥18 years) with coded records for primary immune thrombocytopenia first referenced between January 1st 1992 and November 30th 2007, and having at least one year pre-diagnosis and three months post-diagnosis medical history were matched (1:4 ratio) with 4,280 primary immune thrombocytopenia disease free patients by age, gender, primary care practice, and pre-diagnosis observation time. The baseline prevalence and incidence rate of thromboembolic events were quantified, with comparative risk modelled by Cox’s proportional hazards regression. Results Over a median 47.6 months of follow-up (range: 3.0–192.5 months), adjusted hazard ratios of 1.58 (95% CI, 1.01–2.48), 1.37 (95% CI, 0.94–2.00), and 1.41 (95% CI, 1.04–1.91) were found for venous, arterial, and combined (arterial and venous) thromboembolic events, respectively, when comparing the primary immune thrombocytopenia cohort with the primary immune thrombocytopenia disease free cohort. Further event categorization revealed an elevated incidence rate for each occurring venous thromboembolic subtype among the adult patients with primary immune thrombocytopenia. Conclusions Patients with primary immune thrombocytopenia are at increased risk for venous thromboembolic events compared with patients without primary immune thrombocytopenia.

The High Cost of Prescription Drugs in the United States: Origins and Prospects for Reform

IMPORTANCE The increasing cost of prescription drugs in the United States has become a source of concern for patients, prescribers, payers, and policy makers. OBJECTIVES To review the origins and effects of high drug prices in the US market and to consider policy options that could contain the cost of prescription drugs. EVIDENCE We reviewed the peer-reviewed medical and health policy literature from January 2005 to July 2016 for articles addressing the sources of drug prices in the United States, the justifications and consequences of high prices, and possible solutions. FINDINGS Per capita prescription drug spending in the United States exceeds that in all other countries, largely driven by brand-name drug prices that have been increasing in recent years at rates far beyond the consumer price index. In 2013, per capita spending on prescription drugs was

Practical, Legal, and Ethical Issues in Expanded Access to Investigational Drugs

858 compared with an average of

Autologous 111In-labelled platelet sequestration studies in patients with primary immune thrombocytopenia (ITP) prior to splenectomy: a report from the United Kingdom ITP Registry

400 for 19 other industrialized nations. In the United States, prescription medications now comprise an estimated 17% of overall personal health care services. The most important factor that allows manufacturers to set high drug prices is market exclusivity, protected by monopoly rights awarded upon Food and Drug Administration approval and by patents. The availability of generic drugs after this exclusivity period is the main means of reducing prices in the United States, but access to them may be delayed by numerous business and legal strategies. The primary counterweight against excessive pricing during market exclusivity is the negotiating power of the payer, which is currently constrained by several factors, including the requirement that most government drug payment plans cover nearly all products. Another key contributor to drug spending is physician prescribing choices when comparable alternatives are available at different costs. Although prices are often justified by the high cost of drug development, there is no evidence of an association between research and development costs and prices; rather, prescription drugs are priced in the United States primarily on the basis of what the market will bear. CONCLUSIONS AND RELEVANCE High drug prices are the result of the approach the United States has taken to granting government-protected monopolies to drug manufacturers, combined with coverage requirements imposed on government-funded drug benefits. The most realistic short-term strategies to address high prices include enforcing more stringent requirements for the award and extension of exclusivity rights; enhancing competition by ensuring timely generic drug availability; providing greater opportunities for meaningful price negotiation by governmental payers; generating more evidence about comparative cost-effectiveness of therapeutic alternatives; and more effectively educating patients, prescribers, payers, and policy makers about these choices.

Progress and Hurdles for Follow-on Biologics.

The authors review the FDA policies and procedures that permit some patients with serious conditions to receive investigational drugs before formal product approval and examine the legal and ethical issues associated with expanded access.

Autologous 111 In-labelled platelet sequestration studies in patients with primary immune thrombocytopenia (ITP) prior to splenectomy: a report from the United Kingdom ITP Registry.

While splenectomy is an effective therapy for primary immune thrombocytopenia (ITP), possible complications and observed non‐complete response (CR) in one‐third of patients demonstrate the need for further research into potential pre‐surgical predictors of outcomes. Past investigations into platelet sequestration studies, a hypothesized predictive test, have adopted heterogeneous methods and varied widely with regard to power. By studying patients with primary ITP who underwent autologous 111In‐labelled platelet sequestration studies at Barts and The London NHS Trust between 1994 and 2008, we evaluated the effectiveness of sequestration site in predicting short, medium, and long‐term CR (platelet count >100 × 109/l) to splenectomy through multivariate (gender, age at splenectomy, and mean platelet lifespan) logistic regression modelling. In total, 256 patients with primary ITP underwent scans; 91 (35·5%) proceeded to splenectomy. Logistic regression revealed significant adjusted odds ratios for CR of 7·47 (95% confidence interval [CI], 1·89–29·43) at 1–3 months post‐splenectomy, 4·85 (95% CI, 1·04–22·54) at 6–12 months post‐splenectomy, and 5·39 (95% CI, 1·34–21·65) at last follow‐up (median: 3·8 years [range: 0·5–13·1 years]) in patients with purely or predominantly splenic versus mixed or hepatic sequestration. These findings demonstrate the utility of autologous 111In‐labelled platelet sequestration studies as an adjunct predictive instrument prior to splenectomy.

Experience With the Priority Review Voucher Program for Drug Development

Thanks to a new regulatory pathway created by the 2010 Biologics Price Competition and Innovation Act, the FDA has now approved its first biosimilar drug, filgrastim-sndz. The challenges to achieving savings from follow-on biologics are large but not insurmountable.

Single nucleotide polymorphism (SNP) analysis demonstrates a significant association of tumour necrosis factor-alpha (TNFA) with primary immune thrombocytopenia among Caucasian adults

While splenectomy is an effective therapy for primary immune thrombocytopenia (ITP), possible complications and observed non‐complete response (CR) in one‐third of patients demonstrate the need for further research into potential pre‐surgical predictors of outcomes. Past investigations into platelet sequestration studies, a hypothesized predictive test, have adopted heterogeneous methods and varied widely with regard to power. By studying patients with primary ITP who underwent autologous 111In‐labelled platelet sequestration studies at Barts and The London NHS Trust between 1994 and 2008, we evaluated the effectiveness of sequestration site in predicting short, medium, and long‐term CR (platelet count >100 × 109/l) to splenectomy through multivariate (gender, age at splenectomy, and mean platelet lifespan) logistic regression modelling. In total, 256 patients with primary ITP underwent scans; 91 (35·5%) proceeded to splenectomy. Logistic regression revealed significant adjusted odds ratios for CR of 7·47 (95% confidence interval [CI], 1·89–29·43) at 1–3 months post‐splenectomy, 4·85 (95% CI, 1·04–22·54) at 6–12 months post‐splenectomy, and 5·39 (95% CI, 1·34–21·65) at last follow‐up (median: 3·8 years [range: 0·5–13·1 years]) in patients with purely or predominantly splenic versus mixed or hepatic sequestration. These findings demonstrate the utility of autologous 111In‐labelled platelet sequestration studies as an adjunct predictive instrument prior to splenectomy.

State Initiatives to Control Medication Costs — Can Transparency Legislation Help?

In 2007, Congress authorized a program intended to promote development of new treatments for neglected tropical diseases, conditions that disproportionately affect poor people in developing countries. Neglected tropical diseases lack treatments for many reasons, including attracting little interest from multinational pharmaceutical manufacturers, which preferentially invest in developing products that offer the possibility for more profitable returns. To help overcome such barriers, 2007 federal legislation offering priority review vouchers (PRVs) to companies that sponsored drugs newly approved by the US Food and Drug Administration (FDA) to treat qualifying neglected tropical diseases such as tuberculosis, malaria, schistosomiasis, and yaws. Once granted, the vouchers could be transferred or sold, or redeemed at the FDA to accelerate the regulatory review of a different product (eTable in the Supplement) from the standard 10-month period to the priority 6-month period intended to be reserved for drugs that appear to represent therapeutic advances.1 Earlier access to the US market leads to longer market exclusivity periods and greater revenues. In 2012, PRVs were also made available to sponsors of FDA-approved drugs treating a rare pediatric diseases, with a plan to reexamine the effects of the voucher program in this clinical context after 3 rare pediatric disease vouchers were granted.2 Through August 2015, the FDA has issued 6 vouchers (Table). The first tropical disease voucher was granted in 2009 to Novartis for the antimalarial artemetherlumefantrine,eventhoughatthetimeofFDAapproval,this drug had been approved in more than 80 countries.3 Artemether-lumefantrine qualified because the statute required only that the drug was not yet registered in the United States. To earn the voucher, Novartis submitted to the FDA 8 of the 20 studies it had sponsored from 1993 to 2007 to support approval of the drug abroad. The next tropical disease voucher was for bedaquiline, indicated for multidrug resistant tuberculosis. The surrogate measure of efficacy agreed on by the FDA was the rapidity of conversion of patients’ sputum samples from growth to no growth of the tuberculosis bacillus in culture. Although preapproval studies demonstrated an improvement in this measure among bedaquilinetreated patients, those studies also showed a significantly higher mortality (mostly from tuberculosis) for patients treated with bedaquiline than those who were not (10 of 79 vs 2 of 81).4 Despite these concerns, the FDA approved bedaquiline in 2012 for use “when an effective treatment regimen cannot otherwise be provided.” In 2014, Knight Therapeutics received a voucher for miltefosine, a treatment for leishmaniasis. Miltefosine was originally developed as an anticancer agent in the 1980s but was found to cure visceral leishmaniasis in the late 1990s. Paladin Laboratories acquired rights to the drug in 2008 for