**Objective** Following guidance on data sharing from the
International Committee of Medical Journal Editors,1 Takeda
requires the inclusion of a data sharing statement in most
manuscripts reporting results from interventional clinical
trials. The standard version of this statement indicates that
deidentified patient data will be made available within 3
months to researchers who provide a methodologically sound
proposal. The implementation of this policy for data sharing
by request was assessed by reviewing published articles to determine whether a data sharing statement was included,
modified, or not included, and the reason(s) for not sharing
data were identified.

**Design** To identify articles for inclusion in this study, an
internal publication management system was used. Articles
published online between July 2020 and November 2021
reporting primary or secondary analyses from clinical trials
sponsored by Takeda and reviewed by an internal clinical trial
transparency (CTT) team were included in this analysis. Each
article was assigned to 1 of the following categories: inclusion
of standard data sharing statement, inclusion of modified
data sharing statement, statement indicating there is no plan
to share data, or no data sharing statement.

**Results** A total of 36 interventional clinical trial manuscripts
reviewed by the CTT team were included in the analysis. Of
these, 26 (72%) included a statement outlining data
availability: 11 (31%) used the recommended standard data
sharing statement as outlined in the internal policy, while 15
(42%) contained a modified statement on data availability,
ranging from minor editorial amendments (generally
consistent with the standard statement) to substantial
differences in wording (due to specific journal requirements)
(**Figure 24**). Only 2 articles (6%) contained a statement
indicating that there was no plan to share the data—both were
reporting results from rare disease studies involving very
small numbers of patients, and the reason was concern
regarding the risk of patient reidentification due to the
number of patients. No data sharing statement was included
in 8 articles (22%) for various reasons (**Figure 24**). Of the
journals that published articles without a data sharing
statement, 3 had policies requiring inclusion of a data sharing
statement, while the others had policies allowing and/or
encouraging inclusion of a data sharing statement.

![](https://assets.underline.io/uploads/markdown_image/1/image/54d6a20668a6320b5acb29de3cdbcb27.png)

**Conclusions** Sharing underlying data sets of published
studies is important to promote transparency and facilitate
new research. Following the adoption of a standardized
approach to data sharing by request, most interventional
clinical trial articles in this analysis contained a data sharing
statement. In a few cases (n = 2), the statement indicated that data would not be shared to protect patient privacy in
situations in which deidentification of patient-level data was
not possible.

**Reference**

1. Taichman DB, Sahni P, Pinborg A, et al. Data sharing
statements for clinical trials: a requirement of the
International Committee of Medical Journal Editors. Ann
Intern Med. 2017;167(1):63-65. doi:10.7326/M17-1028
1Takeda Pharmaceuticals International AG, Zürich, Switzerland;
2Takeda Development Center Americas, Inc, Cambridge, MA, USA,
jesse.potash@takeda.com; 

**Funding/Support** This study was sponsored by Takeda
Development Center Americas, Inc.

**Role of the Funder/Sponsor** The sponsor played a role in design
and conduct of the study; collection, management, analysis, and
interpretation of the data; preparation, review, or approval of the
abstract; and decision to submit the abstract for presentation.

![](https://assets.underline.io/uploads/markdown_image/1/image/d566022d4c53ea6c7d9d5d08386723be.png)



Data Sharing Statement Modifications in Manuscripts Reporting Interventional Clinical Trials Sponsored by a Global Biopharmaceutical Company

Substandard and falsified (SF) pharmaceuticals account for an estimated 10% of the pharmaceutical supply chain in low- and middle-income countries (LMICs), where a lack of regulatory and laboratory resources limits the ability to conduct effective post-market surveillance and allows SF products to penetrate the supply chain. The Distributed Pharmaceutical Analysis Laboratory (DPAL) was established in 2014 to expand testing of pharmaceutical dosage forms sourced from LMICs; DPAL is an alliance of academic institutions throughout the United States and abroad that provides high quality, validated chemical analysis of pharmaceutical dosage forms sourced from partners in LMICs. Results from analysis are reported to relevant regulatory agencies and are used to inform purchasing decisions made by in-country stakeholders. As the DPAL program has expanded to testing more than 1000 pharmaceutical dosage forms annually, challenges have surfaced regarding data management and sample tracking. Here, we describe a pilot project between DPAL and ARTiFACTs that applies blockchain to organize and manage key data generated during the DPAL workflow, including a sample’s progress through the workflow, its physical location, provenance of metadata, and lab reputability. Recording time and date stamps with this data will create a permanent and verifiable chain-of-custody for samples. This secure, distributed ledger will be linked to an easy-to-use dashboard, allowing stakeholders to view results and experimental details for each sample in real time and verify the integrity of DPAL analysis data. Introducing this blockchain-based system as a pilot will allow us to test the technology with real users analyzing real samples. Feedback from users will be recorded and necessary adjustments will be made to the system before the implementation of blockchain across all DPAL sites. Anticipated benefits of implementing blockchain for managing DPAL data include efficient management for routing work, increasing throughput, creating a chain of custody for samples and their data in alignment with the distributed nature of DPAL, and using the analysis results to detect patterns of quality within and across brands of products and develop enhanced sampling techniques and best practices.

Securing the chain of custody and integrity of data in a global north-south partnership to monitor the quality of essential medicines

3D printing is emerging as one of the most promising methods to manufacture Pharmaceutical dosage forms as it offers multiple advantages such as personalization of dosage forms, polypill, fabrication of complex dosage forms etc. 3D printing came into existence in 1980s but its use was extended recently to pharmaceutical industry along with the approval of first 3D printed tablet Spritam by FDA in 2015. Spritam was manufactured by Aprecia pharmaceuticals using binder jetting technology. Binder jet 3D printing involves a hopper for powder discharge and printheads for ink jetting. The properties of tablets are highly dependent upon the discharge quality of powder mixture from the hopper and jetting of the ink/binder solution from the printhead nozzle. In this study, numerical models were developed using Discrete element method (DEM) to gain better understanding of the binder jet 3D printing process. The DEM modeling of hopper discharge was performed using in-house DEM code to study the effect of raw material attributes such as powder bed packing density (i.e. particle size, particle density etc.) on the printing process, especially during powder bed preparation. This DEM model was further validated experimentally, and the model demonstrated good agreement with experimental results.

DEM based investigation of powder packing in 3D printing of pharmaceutical tablets

A Hepato-Centric View of Diabetes Management

De novo lipogenesis (DNL) plays a role in the development of hepatic steatosis and non-alcoholic fatty liver disease (NAFLD). In rodent models of both health and lipodystrophy (LD), leptin decreases DNL. In human patients with LD, reduced adipose tissue results in adipokine deficiencies, including lower plasma leptin, which contributes to insulin resistance, dyslipidemia and ectopic accumulation of triglycerides (TG). The mechanisms by which leptin regulates serum and hepatic-TG are not well elucidated. Studying patients with LD before and after leptin therapy provides an important clinical model for understanding leptin’s effect on DNL. We hypothesized that leptin treatment in lipodystrophic patients would decrease DNL by decreasing insulin resistance and glycemia, resulting in reduced circulating and hepatic-TG.Leptin-naïve patients with LD (n=11) were treated with recombinant leptin (metreleptin) for 6 months. All measurements were performed after an 8-12 hr fast. The % of TG in TG-rich lipoproteins (TRLP-TG) derived from DNL (% DNL) was measured using body water labeling (oral D2O) of TG and mass spectrometry analysis. Absolute DNL was calculated as the product of TRLP-TG and % DNL. HbA1c and serum-TG were measured biochemically, hepatic-TG by MRI, and total body and hepatic insulin sensitivity measured during a hyperinsulinemic-euglycemic clamp.DNL decreased after metreleptin: % DNL from 22.8±6.8 to 9.1±5.1% (p=0.0008) and absolute DNL from 54.2±32.1 to 8.6±6.5 mg/dl (p=0.003). TRLP-TG decreased from (median [interquartile range]) 160 [107, 280] to 98 [66, 147] mg/dl (p=0.01). Total body and hepatic insulin sensitivity increased from 3.7 [3.0, 7.3] to 8.4 [5.1,10.6] mg/kgFFM/min (p=0.03) and from 61.0 [48.5, 69.3] to 84.7 [75.2, 107.6] % (p =0.01), respectively. HbA1c decreased from 8.6±1.8 to 7.1±1.4% (p=0.04), hepatic-TG decreased from 17.6±11.9 to 10.3±9.1% (p=0.02), and serum-TG from 386 [216, 686] to 223 [118, 497] mg/dl (p=0.06). DNL correlated negatively with insulin sensitivity both before (r=-0.73, p=0.03) and after (r=-0.85, p=0.004) metreleptin. DNL correlated positively with hepatic-TG before (r=0.70 p=0.03) and tended to correlate after metreleptin (r=0.65, p=0.06). The change in DNL correlated with change in serum-TG (r=0.77, p=0.04) but not the change in hepatic-TG (p=0.80).We show here for the first time that 6 months of metreleptin treatment in humans with LD decreased DNL by 84% and was associated with reductions in glycemia and improved peripheral and hepatic insulin sensitivity. These data indicate a strong link between metreleptin’s effects to increase clearance of blood glucose by peripheral tissues and reduce hepatic carbohydrate flux, resulting in DNL reductions. This led to lowered hepatic steatosis and dyslipidemia and suggests treatments that target multi-organ insulin resistance may lead to decreased NAFLD and cardiovascular risk.

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Data Sharing Statement Modifications in Manuscripts Reporting Interventional Clinical Trials Sponsored by a Global Biopharmaceutical Company

Securing the chain of custody and integrity of data in a global north-south partnership to monitor the quality of essential medicines

DEM based investigation of powder packing in 3D printing of pharmaceutical tablets

A Hepato-Centric View of Diabetes Management

Leptin Decreases De Novo Lipogenesis in Lipodystrophic Patients

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