Pharmaceutical Funding Research Articles

Evaluation of a risk-sharing agreement for atezolizumab treatment in patients with non-small cell lung cancer: a strategy to improve access in low-income countries.

Using immune checkpoint inhibitors (IO) is a promising approach to maximize clinical benefits for patients with non-small cell lung cancer (NSCLC). PD-L1 expression serves as a predictive factor for treatment outcomes with IO. However, the high cost of this treatment creates significant barriers to access. Substantial evidence demonstrates the sustained clinical benefits experienced by patients who respond to immunotherapy. While IOs show promise in NSCLC treatment, their high cost poses access barriers. This study focused on a prospective cost analysis conducted at a high-specialty health facility to assess the economic implications of implementing a risk-sharing agreement (RSA) for atezolizumab in NSCLC. The study included 30 patients with advanced NSCLC, with the pharmaceutical company funding the initial cycles. If patients responded, a government program covered costs until disease progression. A median progression-free survival of 4.67 months across populations, rising to 9.4 months for responders. The 2-year overall survival rate for the response group was 64%, significantly higher than for non-response. Without an RSA, a total treatment cost of $881 859.36 ($29 395.31/patient) was reported, compared to $530 467.12 ($17 682.24/patient) with an RSA, representing a 40% cost reduction. In responders, the average cost per year of life per patient dropped by 22%. Risk-sharing, assessed through non-parametric tests, showed a statistically significant difference in pharmacological costs (P < .001). Implementing RSAs can optimize resource allocation, making IO treatment more accessible, especially in low-income countries.

Pharmacological and ethical comparisons of lung cancer medicine accessibility in Australia and New Zealand

Gaps in funded cancer medicines between New Zealand and Australia can have significant implications for patients and their families. Pharmac, the New Zealand pharmaceutical funding agency, has been criticised for...

Pharmaceutical company funding of cancer patient advocacy organizations in the Netherlands

BackgroundFinancial conflicts of interest (FCOI) of medical professionals and associated organizations with pharmaceutical companies (pharma) might contribute to the use of low value oncological treatments. Value criteria for oncological drug approvals in the Netherlands have recently become more stringent leading to objections by cancer patient advocacy organizations (cPAOs). Considering the importance of cPAOs input in cancer patient care we analyzed whether pharma funding of cPAOs occurs in the Netherlands. MethodsThe cPAO websites and available annual reports were evaluated for disclosure of pharma funding for the years 2021 and 2022. Also, data from the Dutch Healthcare Transparency Registry (DHTR) were extracted. ResultsTwenty-one of 34 (61.8 %) cPAOs received pharma funding (with 20 registered in the DHTR), and for 13 (29.4 %) cPAOs no reporting of pharma funding could be found. Three of the cPAOs disclosed pharma funding directly on their main website. Online educational material was available from 22 cPAOs on their websites with pharma funding disclosed on the educational material in 5. The total registered amount of pharmaceutical funding was €667,232.00 in 2021 and €536,098.00 in 2022. The median (and interquartile ranges) DHTR registered amount of support per cPAO that received funding in the studied period was €23,799.50 (14,823.75–84,663.30). The most common funding category as defined in the DHTR was project sponsorship. ConclusionsFinancial support by the pharmaceutical industry is common for Dutch cPAOs. Given the importance of cPAOs and their objective input in the societal debate on the availability of cancer drugs, the potential influence of pharma sponsoring should be critically evaluated.

Appendectomy versus antibiotic treatment for acute appendicitis.

Acute appendicitis is one of the most common emergency general surgical conditions worldwide. Uncomplicated/simple appendicitis can be treated with appendectomy or antibiotics. Some studies have suggested possible benefits with antibiotics with reduced complications, length of hospital stay, and the number of days off work. However, surgery may improve success of treatment as antibiotic treatment is associated with recurrence and future need for surgery. To assess the effects of antibiotic treatment for uncomplicated/simple acute appendicitis compared with appendectomy for resolution of symptoms and complications. We searched CENTRAL, MEDLINE, Embase, and two trial registers (World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov) on 19 July 2022. We also searched for unpublished studies in conference proceedings together with reference checking and citation search. There were no restrictions on date, publication status, or language of publication. We included parallel-group randomised controlled trials (RCTs) only. We included studies where most participants were adults with uncomplicated/simple appendicitis. Interventions included antibiotics (by any route) compared with appendectomy (open or laparoscopic). We used standard methodology expected by Cochrane. We used GRADE to assess the certainty of evidence for each outcome. Primary outcomes included mortality and success of treatment, and secondary outcomes included number of participants requiring appendectomy in the antibiotic group, complications, pain, length of hospital stay, sick leave, malignancy in the antibiotic group, negative appendectomy rate, and quality of life. Success of treatment definitions were heterogeneous although mainly based on resolution of symptoms rather than incorporation of long-term recurrence or need for surgery in the antibiotic group. We included 13 studies in the review covering 1675 participants randomised to antibiotics and 1683 participants randomised to appendectomy. One study was unpublished. All were conducted in secondary care and two studies received pharmaceutical funding. All studies used broad-spectrum antibiotic regimens expected to cover gastrointestinal bacteria. Most studies used predominantly laparoscopic surgery, but some included mainly open procedures. Six studies included adults and children. Almost all studies aimed to exclude participants with complicated appendicitis prior to randomisation, although one study included 12% with perforation. The diagnostic technique was clinical assessment and imaging in most studies. Only one study limited inclusion by sex (male only). Follow-up ranged from hospital admission only to seven years. Certainty of evidence was mainly affected by risk of bias (due to lack of blinding and loss to follow-up) and imprecision. Primary outcomes It is uncertain whether there was any difference in mortality due to the very low-certainty evidence (Peto odds ratio (OR) 0.51, 95% confidence interval (CI) 0.05 to 4.95; 1 study, 492 participants). There may be 76 more people per 1000 having unsuccessful treatment in the antibiotic group compared with surgery, which did not reach our predefined level for clinical significance (risk ratio (RR) 0.91, 95% CI 0.87 to 0.96; I2 = 69%; 7 studies, 2471 participants; low-certainty evidence). Secondary outcomes At one year, 30.7% (95% CI 24.0 to 37.8; I2 = 80%; 9 studies, 1396 participants) of participants in the antibiotic group required appendectomy or, alternatively, more than two-thirds of antibiotic-treated participants avoided surgery in the first year, but the evidence is very uncertain. Regarding complications, it is uncertain whether there is any difference in episodes of Clostridium difficile diarrhoea due to very low-certainty evidence (Peto OR 0.97, 95% CI 0.24 to 3.89; 1 study, 1332 participants). There may be a clinically significant reduction in wound infections with antibiotics (RR 0.25, 95% CI 0.09 to 0.68; I2 = 16%; 9 studies, 2606 participants; low-certainty evidence). It is uncertain whether antibiotics affect the incidence of intra-abdominal abscess or collection (RR 1.58, 95% CI 0.61 to 4.07; I2 = 19%; 6 studies, 1831 participants), or reoperation (Peto OR 0.13, 95% CI 0.01 to 2.16; 1 study, 492 participants) due to very low-certainty evidence, mainly due to rare events causing imprecision and risk of bias. It is uncertain if antibiotics prolonged length of hospital stay by half a day due to the very low-certainty evidence (MD 0.54, 95% CI 0.06 to 1.01; I2 = 97%; 11 studies, 3192 participants). The incidence of malignancy was 0.3% (95% CI 0 to 1.5; 5 studies, 403 participants) in the antibiotic group although follow-up was variable. Antibiotics probably increased the number of negative appendectomies at surgery (RR 3.16, 95% CI 1.54 to 6.49; I2 = 17%; 5 studies, 707 participants; moderate-certainty evidence). Antibiotics may be associated with higher rates of unsuccessful treatment for 76 per 1000 people, although differences may not be clinically significant. It is uncertain if antibiotics increase length of hospital stay by half a day. Antibiotics may reduce wound infections. A third of the participants initially treated with antibiotics required subsequent appendectomy or two-thirds avoided surgery within one year, but the evidence is very uncertain. There were too few data from the included studies to comment on major complications.

Medical Writing Bias in Myeloma Clinical Research: A Comprehensive Analysis

Background Previous studies investigating associations between pharmaceutical funding and clinical trial results have found ties between pharmaceutical sponsorship and results favoring the sponsor's interests. There are no studies examining potential sponsorship bias within the field of multiple myeloma (MM). Addressing sponsorship bias is essential to ensure reliability, validity, and ethical conduct of clinical research in the field of MM. This study analyzes potential sponsorship bias in MM specifically regarding use of medical writers that are employees of or directly funded by pharmaceutical companies among published clinical research studies of drugs approved to treat MM from January 2000 - March 2023. Methods Clinical study papers from PubMed between January 2000 and March 2023 were analyzed if at least 1 of the 10 following drugs were evaluated: bortezomib (BORT), carfilzomib (CARF), daratumumab (DARA, elotuzumab (ELO), isatuximab (ISA), ixazomib (IXA), lenalidomide (LEN), panobinostat (PAN), pomalidomide (POM), and selinexor (SELI), and the manufacturer of the drug(s) sponsored the study (N=1466). Papers were considered to contain potential medical writing bias if the paper was written by employees of the manufacturer of the drug(s) or medical writers directly funded by the manufacturer. Papers were analyzed by year, drug, and journal in which it was published. Results From 2000 - March 2006, no potential writing bias occurred. In 2007, it first became apparent when 4% (2/53) of papers showed bias which has increased as follows: 2008 - 2012 [14% (41/300)], 2013 - 2017 [25% (100/405)], 2018-2022 [33% (171/521)], and increased to 44% (12/27) in 2023. We also analyzed writing bias according to the specific drugs from January 2000 - March 2023 with the following rates of potential bias: ISA 93% (26/28), IXA 77% (36/47), DARA 76% (63/83), ELO 71% (17/24), SELI 62% (8/13), POM 55% (27/49), PAN 50% (9/18), BORT 47% (47/100), LEN 46% (75/163) and CARF 32% (15/47). Potential writing bias was also determined according to the specific medical journal in which the paper was published from 2000 - March 2023. Blood and British Journal of Haematology have the highest number of potentially biased manuscripts at 42 and 30, respectively, representing 25% (42/142) and 21% (30/143) of the papers published, respectively. New England Journal of Medicine and Lancet have high percentages of potential writing bias at 33% (9/27) and 46% (6/13), respectively. Many journals have 100% (n=6) but these sources only had 1 paper meeting the study criteria. Conclusion Since 2000, we have observed an alarming increase in the rate of clinical research papers evaluating drugs approved to treat MM which have been written by pharmaceutical company employees or medical writers directly funded by them. Notably, nearly half (44%) of papers published this year showed potential writing bias. Rates varied greatly between different drugs with ISA, IXA and DARA showing the highest rates of writing bias whereas BORT, LEN and CARF showed the lowest rates. Specific journals including Blood and British Journal of Haematology both show high numbers of papers with potential writing bias; and, furthermore, a high percentage of papers published in high impact journals such as the New England Journal of Medicine and Lancet show this type of potential bias. This practice of allowing medical writing to be carried out by those with direct ties to the pharmaceutical company is likely to result in the publication of papers with results and conclusions regarding the efficacy and safety of drugs that are biased which compromises their scientific integrity and objectivity.

Obinutuzumab Can Be Administered as a 90-minute Short Duration Infusion in Patients With Previously Untreated Follicular Lymphoma: GAZELLE End of Induction Analysis.

Obinutuzumab Can Be Administered as a 90-minute Short Duration Infusion in Patients With Previously Untreated Follicular Lymphoma: GAZELLE End of Induction Analysis.

335 (PB115) - Treatment strategies based on the molecular subtypes of transformed small cell lung cancer (t-SCLC)

Background: Small-cell transformation is one of the resistance mechanisms (4–14%) to Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) in EGFR-mutant lung adenocarcinomas (LADCs). Although bi-allelic inactivation of TP53 and RB1 is identified as the major genetic footprint of t-SCLC, the molecular driving force to the small cell transformation is still unknown. Recent studies to classify the genetic subtypes of de novo SCLC have guided subtype-specific treatment strategies. Here, we characterized the subtypes of nine t-SCLC cases and two t-SCLC patient-.derived cell lines. Material and methods: We compared RNA profiles of two t-SCLC cell lines (SNU-2962A and SNU-4505) with 57 LADC and 48 SCLC cell lines from the Cancer Cell Line Encyclopedia (CCLE). We investigated the molecular subtypes of t-SCLC and their therapeutic strategies. SNU-2962A and SNU-4505 cells were seeded in 384-well plates containing the siRNA of 709 kinases for 72hr. Furthermore, cell viability assays were performed on drugs targeting genes suggested as subtype-specific vulnerabilities in de novo SCLC. We also examined four subtype markers (ASCL1, NEUROD1, POU2F3, and YAP1) by immunohistochemistry (IHC) in t-SCLC tumor samples of 5 EGFR-mutant and 3 EGFR wild-type patients. Results: RNA-seq results showed that the SNU-2962A cell line was classified into the NEUROD1 subtype with high expression of neuroendocrine genes and typical SCLC markers (SYP, CHGA, and NCAM1). In contrast, the SNU-4505 cell line, classified as a YAP1 subtype, has EMT characteristics with low neuroendocrine and SCLC marker expressions. A dimension reduction plot of RNA expression showed that the SNU-2962A cell line was clustered close to the NEUROD1 subtype. The SNU-4505 cell line was located close to LADC with other SCLC-YAP1 cell lines. We tested the drug sensitivities of the targets based on kinome screening and the previously proposed subtype-specific vulnerabilities. In both cell lines, PLK1 knockdown significantly reduced cell viability. SNU-2962A cell line was sensitive to bromodomain and extra-terminal (BET) inhibitors, and the apoptotic pathway was activated through Caspase signaling. SNU-4505 cell lines did not show sensitivity to the drugs tested except for paclitaxel. Subtype classification by IHC in patient samples was positive for at least one subtype marker. In most cases, ASCL1 or NEUROD1 that exhibits neuroendocrine characteristics was identified as a dominant subtype. In addition, there was no difference of subtypes, according to the EGFR status. Conclusions: Our in vitro studies suggest that EGFR-mutant t-SCLC can be classified into subtypes like de novo SCLC. NEUROD1-positive SNU-2962A cell line was sensitive to BET inhibition, whereas YAP1-positive SNU-4505 cell line was only sensitive to paclitaxel, suggesting a subtype-specific therapeutic strategy in t-SCLC. Conflict of interest: Advisory Board: T.M. Kim reports advisory role or honorarium from AstraZeneca/MedImmune, Bayer, Boryung, Hanmi, Janssen, Novartis, Roche/Genentech, Sanofi, and Takeda. D.W. Kim reports Uncompensated consultation or advisory role from Amgen, AstraZeneca, BMS/ONO Pharmaceuticals, Daiichi-Sankyo, GSK, Janssen, Meck, MSD, Oncobix, Pfizer, SK Biopharm, and Takeda Corporate-sponsored Research: T.M. Kim reports research funding from Amgen, AstraZeneca/Medimmune, Boehringer-Ingelheim, BMS, Hanmi, Janssen, Merck, MSD, Novartis, Regeneron, Roche/Genentech, Sanofi, and Takeda. D.W. Kim reports research funding from Alpha Biopharma, Amgen, Astrazeneca/Medimmune, Boehringer-Ingelheim, BMS, Bridge BioTherapeutics, Chong Keun Dang, Daiichi-Sankyo, GSK, Hanmi, Janssen, Merck, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, and Yuhan and laboratory research funding from InnoN. Other Substantive Relationships: D.W. Kim reports travel and accomodation support for advisory board meeting attendance from Amgen, Daiichi-Sankyo and medical writing assistance from Amgen, AstraZeneca, Boehringer-Ingelheim, BMS, Chong Keun Dang, Daiichi-Sankyo, GSK, Pfizer, MSD, Meck, Novartis, Roche, Takeda, and Yuhan.

33567 Overview of the systematic reviews with network meta-analysis evaluating the efficacy or safety of the systemic treatments in moderate-to-severe psoriasis

Background: Network meta-analyses (NMAs) have become successful in addressing gaps in comparative effectiveness of systemic treatments (ST) in psoriasis. Their increasing number carries a risk of overlap and reproducibility issues. We aimed to assess redundancy across these NMAs and to describe their characteristics. Methods: We considered all systematic reviews with NMAs of randomized controlled trials that included adult patients with moderate-to-severe psoriasis and that evaluated the efficacy and/or safety of ST compared with placebo or an active comparator. Four electronic databases were searched up to 02/25/2021. Our main outcome was the number of redundant NMAs and their overlaps. We described their characteristics, the confidence in the results, the reporting issues, the studies’ funding, and the presence of spin. Results: In total, 47 redundant NMAs were included. Two (4%) included all available treatments. Both efficacy and safety were evaluated in 14/47 (30%) NMAs and both short and long-term evaluations were assessed in 5/47 (11%). Confidence in the results was critically low for 39/47 (83%) NMAs. Only 10/47 (23%) registered a protocol. Pharmaceutical funding was present in 26/47 NMAs (55%). Spin was present in all of the abstracts and reporting was poor in most of them according to the PRISMA-checklist. Almost half of the NMA failed to check for heterogeneity or consistency. Discussion: Our overview showed heterogeneous methods and poor confidence in the results in a majority of the redundant NMAs, further distorted by reporting issues and spin. Clinicians need to interpret NMAs with caution when looking for the most reliable evidence.

The Next Pandemic

The Next Pandemic

Overlapping network meta-analyses on psoriasis systemic treatments, an overview: quantity does not make quality.

Network meta-analyses (NMAs) have become successful in addressing gaps in the comparative effectiveness of systemic treatments in moderate-to-severe psoriasis. However, their increasing number carries both a risk of overlap and reproducibility issues that can hamper clinical decision-making. In this overview, we aimed to assess redundancy across these NMAs and to describe their characteristics. We considered all systematic reviews with NMAs of randomized controlled trials that included adult patients with moderate-to-severe psoriasis and that evaluated the efficacy and/or safety of systemic treatments compared with placebo or with an active comparator. PubMed/MEDLINE, Epistemonikos, PROSPERO and the Evidence update of the Centre of Evidence-Based Dermatology of the University of Nottingham were searched up to 25 February 2021. Our main outcome was the number per year of redundant NMAs and the extent of their overlap. We also described their features, especially, the confidence in the results of the reviews, the funding of the studies and the presence of spin (a description that overstates efficacy and/or understates harm), reporting issues and methodological characteristics. In total, 47 redundant NMAs were included. Only two of 47 (4%) included all available treatments. Both efficacy and safety were evaluated in 14 of 47 (30%) NMAs and both short- and long-term evaluations were assessed in five of 47 (11%). Confidence in the results was critically low for 39 of 47 (83%) NMAs and only 10 of 47 (21·3%) registered a protocol. Twenty-six of 47 NMAs (55%) received pharmaceutical funding. Contract research organizations were involved in 19 of 47 (40%) NMAs. Reporting was poor across most of the NMA abstracts and spin was present in all of the abstracts. Almost half of the NMAs failed to consider important limitations such as heterogeneity (considered in 32%) or consistency (considered in 66%). In addition to a duplication of efforts, our overview showed heterogeneous methods and poor confidence in the results in a majority of the included NMAs, further distorted by reporting issues and spin. Clinicians need to interpret NMAs with caution when looking for the most reliable and comprehensive evidence.

Fraud and Deceit in Medical Research

Fraud and Deceit in Medical Research

Graph Neural Networks as a Potential Tool in Improving Virtual Screening Programs.

Despite the increasing number of pharmaceutical companies, university laboratories and funding, less than one percent of initially researched drugs enter the commercial market. In this context, virtual screening (VS) has gained much attention due to several advantages, including timesaving, reduced reagent and consumable costs and the performance of selective analyses regarding the affinity between test molecules and pharmacological targets. Currently, VS is based mainly on algorithms that apply physical and chemistry principles and quantum mechanics to estimate molecule affinities and conformations, among others. Nevertheless, VS has not reached the expected results concerning the improvement of market-approved drugs, comprising less than twenty drugs that have reached this goal to date. In this context, graph neural networks (GNN), a recent deep-learning subtype, may comprise a powerful tool to improve VS results concerning natural products that may be used both simultaneously with standard algorithms or isolated. This review discusses the pros and cons of GNN applied to VS and the future perspectives of this learnable algorithm, which may revolutionize drug discovery if certain obstacles concerning spatial coordinates and adequate datasets, among others, can be overcome.

Perceived Satisfaction of Public Health Facilities’ with the Quality of Logistics Service Provided by Pharmaceutical Fund and Supply Agency Bahirdar Hub, Northwest Ethiopia: Descriptive Study

Aim: This study aimed to investigate the satisfaction of public health facilities in the quality of logistics services received from the Pharmaceutical Fund and Supply Agency Bahirdar hub. Methodology: A descriptive research design has been used for assessing satisfaction. The data collection was carried out from 28 April/20, 2019 to – 20 June/2019. All hospitals in the study area were selected purposively and simple random sampling with a lottery method was used to pick health centers from the sampling frame. A total of 64 participants were selected for data collection. Epidata software and SPSS version 20 were used for data entry and analysis, respectively. Frequency distribution, arithmetic means, and percentages were calculated. Result: All questionaries were successfully filled and returned. It discovered that 41(64.1%) of respondents were neither satisfied nor dissatisfied, while 19(29.7%) considered themselves as ‘satisfied’ with the overall quality of the logistics services they received. Besides, 3(4.7%) of the respondents said they were ‘dissatisfied’ with the service and 1(1.6%) was highly dissatisfied with the service. From all dimensions, the condition of pharmaceutical delivery and product availability received the highest (3.749) and the lowest mean score (2.885), respectively. Conclusion: The overall perceived satisfaction of public health facilities with the quality of logistics service given by the Pharmaceutical Fund and Supply Agency Bahirdar hub was in the middle of the continuum, with the mean score close to the 5-Likert scale midpoint.

Health care costs and resource utilization among commercially insured adult patients with hemophilia A managed with FVIII prophylaxis in the United States.

BACKGROUND: Standard of care for patients with severe hemophilia A (HA) is life-long prophylaxis with factor VIII (FVIII) concentrate or other hemostatic agents. Published literature highlights a wide range of treatment costs for patients with HA. OBJECTIVE: To estimate average annual health care costs and resource utilization for a cross-section of adult patients managed with FVIII concentrate prophylaxis using recent data from a large US commercial claims database. METHODS: Adult males with 1 or more claim with HA diagnosis, continuous commercial plan enrollment, and 4 or more FVIII prescription dispenses during 12 months were identified from IBM MarketScan Research Database from January 2013 to September 2019, excluding those with FVIII inhibitors, an HIV/AIDS diagnosis, or diagnosis and treatment for hepatitis B or C. Patients were classified as using FVIII prophylaxis if they met any of the following definitions: (1) 6 or more FVIII dispenses, (2) a gap of 60 days or less between dispenses, and (3) at least 273 days supply in the 12-month period. Additionally, subgroups of patients meeting each individual definition were examined, with some patients included in all 3 subgroups. RESULTS: The overall cohort included 411 patients who met 1 or more of the 3 definitions, with a mean age of 28.9 years. Subgroups of 401, 325, and 237 patients met the first, second, and third FVIII prophylaxis definitions, respectively. Per-patient mean (SD) annual all-cause health care costs were $654,571 ($380,762) in the overall cohort and ranged from $650,065 ($382,196) to $759,661 ($387,040) among subgroups. Cost of FVIII concentrate accounted for more than 96% of total costs in the overall cohort and in each subgroup. Cost of FVIII in the overall cohort varied according to type of concentrate, with the highest among patients who were treated with both standard and extended half-life (SHL and EHL) FVIII ($784,945), followed by EHL FVIII only ($708,928), SHL FVIII only ($647,800), and plasma-derived FVIII ($535,614). The most common treatment type was SHL FVIII only (45.7% of all patients). In the overall cohort, the majority had 1 or more outpatient visits (94.9%), while emergency department visits, hospital admissions, and home health visits occurred less frequently (27.0%, 7.1%, and 7.1%, respectively). CONCLUSIONS: Commercially insured patients with HA incur substantial all-cause annual health care costs, with FVIII concentrate accounting for a majority of costs. DISCLOSURES: This study was funded by BioMarin Pharmaceutical Inc, which was involved in the protocol development, analysis plan development, data interpretation, manuscript preparation, and publication decisions. All authors contributed to protocol development, analysis plan development, data interpretation, and manuscript development and maintained control over the final content. Thornburg has received professional fees from BioMarin Pharmaceutical, CSL Behring, Genentech, Novo Nordisk, Sanofi Genzyme, HEMA Biologics, and Spark Therapeutics and institutional research funding from BioMarin Pharmaceutical, Novo Nordisk, and Sanofi Genzyme. Adamski, Cook, and Sendhil are employees of Analysis Group, a consulting company that was contracted by BioMarin Pharmaceutical to conduct this study and develop the manuscript. Vembusubramanian is a former employee of Analysis Group. Hinds, Chen, and Sammon are employees and shareholders of BioMarin Pharmaceutical. Solari is a former employee of BioMarin Pharmaceutical. Garrison has received consulting fees from BioMarin Pharmaceutical and Analysis Group. Croteau has received professional fees from BioMarin Pharmaceutical, Bayer, CSL Behring, HEMA Biologics, and Pfizer and institutional research funding from Novo Nordisk and Spark Therapeutics.

Characteristics of Cost-effectiveness Studies for Oncology Drugs Approved in the United States From 2015-2020

Increasingly, cost-effectiveness analyses are being done to determine the value of rapidly increasing oncology drugs; however, this assumes that these analyses are unbiased. To analyze the characteristics of cost-effectiveness studies and to determine characteristics associated with whether an oncology drug is found to be cost-effective. This retrospective cross-sectional study included 254 cost-effectiveness analyses for 116 oncology drugs that were approved by the US Food and Drug Administration from 2015 to 2020. Each drug was analyzed for the incremental cost-effectiveness ratio per quality-adjusted life year, the funding of the study, the authors' conflict of interest, the threshold of willingness-to-pay, from what country's perspective the analysis was done, and whether a National Institute for Health and Care Excellence cost-effectiveness analysis had been done. The main outcome was the odds of a study concluding that a drug was cost-effective. There were 116 drug approvals with 254 studies and country perspectives. Of the country perspectives, 132 (52%) were from the US. Forty-seven of 78 drugs with cost-effective studies had been shown to improve overall survival, whereas 15 of 38 of drugs without a cost-effectiveness study had been shown to improve overall survival. Having a study funded by a pharmaceutical company was associated with higher odds of a study concluding that a drug was cost-effective than studies without funding (odds ratio, 41.36; 95% CI, 11.86-262.23). In this cross-sectional study, pharmaceutical funding was associated with greater odds that an oncology drug would be found to be cost-effective. These findings suggest that simply disclosing potential conflict of interest is inadequate. We encourage cost-effectiveness analyses by independent groups.

Factors of feasibility: an interview study of physicians\u2019 experiences of expanded access to investigational drugs in three countries

Seriously ill patients who have exhausted all approved treatment regimens and who cannot be enrolled in clinical trials may resort to expanded access programmes in order to gain access to unapproved, investigational drugs. It seems that in some countries, expanded access to investigational drugs is offered in clinical practice on a more routine basis than in other countries. This study is the first to investigate the experiences of physicians with expanded access to investigational drugs in different healthcare systems, with a focus on factors that facilitate or hinder expanded access. Semi-structured interviews (n = 36) were carried out with medical specialists in the Netherlands (n = 14), Turkey (n = 9) and the United States of America (n = 13), and analysed thematically. This study identifies five sets of factors pointed out by physicians that determine the degree to which expanded access to investigational drugs is deemed feasible in clinical practice: the suitability of investigational treatments, the application process, hospital policies, support by pharmaceutical companies, and funding and reimbursement arrangements. Based on the interviews conducted, we conclude that, while legally allowed and technically possible, expanded access is not always feasible for—and not always considered an option by—treating physicians. This is mainly due to lack of familiarity with expanded access, the extensive time and effort required for the application process, willingness or ability of pharmaceutical companies to supply the drugs, and funding issues.

Sex Selection Bias in Schizophrenia Antipsychotic Trials—An Update Systematic Review

The lack of female participation in antipsychotic trials for schizophrenia poses an important issue regarding its applicability, with direct and real-life repercussions to clinical practice. Here, our aim is to systematically review the sampling sex bias among randomized clinical trials (RCTs) of second-generation antipsychotics—namely risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole—as an update to a previous 2005 review. We searched MEDLINE and the Cochrane database for studies published through 7 September 2020 that assessed adult samples of at least 50 subjects with a diagnosis of schizophrenia, schizophrenia spectrum disorder, or broad psychosis, in order to investigate the percentage of women recruited and associated factors. Our review included 148 RCTs, published from 1993 to 2020, encompassing 43,961 subjects. Overall, the mean proportion of women was 34%, but only 17 trials included 50% or more females. Younger samples, studies conducted in North America, pharmaceutical funding and presence of specific exclusion criteria for women (i.e., pregnancy, breast-feeding or lack of reliable contraceptive) were associated with a lower prevalence of women in the trials. Considering the possible different effects of antipsychotics in both sexes, and our lack of knowledge on the subject due to sampling bias, it is imperative to expand actions aimed at bridging this gap.

Perceived Satisfaction of Public Health Facilities’ with the Quality of Logistics Service Provided by Pharmaceutical Fund and Supply Agency Bahirdar Hub, Northwest Ethiopia: Descriptive Study

Aim: This study aimed to investigate the satisfaction of public health facilities in the quality of logistics services received from the Pharmaceutical Fund and Supply Agency Bahirdar hub. Methodology: A descriptive research design has been used for assessing satisfaction. All hospitals in the study area were selected purposively and simple random sampling with a lottery method was used to pick health centers from the sampling frame. A total of 32 health facilities (i.e. 6 hospitals and 26 health centers) have been chosen for this research. Epidata software and SPSS version 20 were used for data entry and analysis, respectively. Frequency distribution, arithmetic means, and percentages were calculated. Result: This research discovered that 41(64.1%) of respondents were neither satisfied nor dissatisfied, while 19(29.7%) considered themselves as 'satisfied' with the overall quality of the logistics services they received. Besides, 3(4.7%) of the respondents said they were 'dissatisfied' with the service and 1(1.6%) was highly dissatisfied with the service. Conclusion: The overall perceived satisfaction of public health facilities with the quality of logistics service given by the Pharmaceutical Fund and Supply Agency Bahirdar hub was in the middle of the continuum, with the mean score close to the 5-Likert scale midpoint

Retos y desafíos de la investigación clínica independiente

Pharmaceutical companies fund most clinical trials on drugs. However, there are clinical issues that might not be a priority from a commercial point of view, but that should certainly be addressed, given their importance for patients and society in general. Independent clinical research represents a fundamental pillar here and its basic element is investigator-initiated studies/trials. In these studies, it is the researcher who conceives the idea, develops the project and also acts as the sponsor. Most researchers are familiar with participating as collaborators in studies sponsored by pharmaceutical companies. In these studies, the company is in charge of all the scientific, legal and financial aspects, leaving the responsibility of the researcher mainly limited to the inclusion of patients and compliance with the protocol. On the contrary, the start-up and development of an independent research study requires considerable resources – of knowledge, money and time – and careful planning on the part of the researcher. In this manuscript, we will review the main characteristics of the studies initiated by the researcher and their fundamental differences with those sponsored by the pharmaceutical industry. We will also outline what its strengths and limitations are. Finally, we will propose some solutions to the main challenges they pose. Our ultimate goal is to stimulate potential researchers to undertake the challenge of conducting an independent clinical research project.

THE TESTING OF EFFICIENT MARKET HYPOTHESES: A STUDY OF INDIAN PHARMACEUTICAL INDUSTRY

The purpose of this study is to test whether the Indian pharmaceutical companies support efficient market hypotheses (EMH) and examine the efficiency of the Indian stock market in three forms, i.e., the weak, the semi-strong, and the strong form of market efficiency. For testing the weak form of efficiency, researchers collected stock price data of 10 listed pharmaceutical companies for the past six years, from 2012 to 2017 from the NSE website, and conducted a run test. To test the efficiency of semi-strong form, researchers collected data on the announcement of events like buyback, stock split, rights issue, dividend, bonus issue. They conducted an event study on the data. For testing the strong form of efficiency, researchers collected data consisting of NAV of some mutual funds (pharmaceutical funds) and the returns of a benchmarking index to compare. The study concludes that the pharmaceutical companies and Indian stock market is efficient in the weak form of EMH and not efficient in the semi-strong and strong form of EMH.