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Over and over there are reports about the increasing rise of antibiotic-resistant bugs. Even as the number of resistant bacteria increases, the number of companies developing new types of antibiotics is decreasing.

Earlier this year, a coalition of healthcare organizations, along with U.S. antibiotic developers, issued a letter to Congress calling for a bundle of economic incentives that would be used to kick start the stagnant pipelines of antibiotic drug developers. In the letter, the 26 signees, which includes companies like Merck, GlaxoSmithKline and Pfizer, express concern over the continued rise of antibiotic-resistant bacteria.

“Antibiotics underpin modern medicine, and antibiotic resistance jeopardizes the entire health system… New resistance threats continuously emerge, rendering many existing drugs ineffective and shrinking our treatment arsenal,” the letter says.

Last year, the World Health Organization’s Global Antimicrobial Surveillance System (GLASS), found widespread antibiotic resistance among 500,000 people with suspected bacterial infections in 22 countries. According to the U.S. Centers for Disease Control and Prevention (CDC), each year in the United States, about two million people develop an antibiotic-resistant infection. Of those, approximately 23,000 people die. There are some estimates that by 2030, up to 10 million people across the globe will die annually due to these superbugs.

The letter goes on to point out to the small number of antibiotic medications in development that have the potential to impact the most critical Gram-negative pathogens on the World Health Organization’s priority list of antibiotic-resistant pathogens. While the threat of these pathogens is real, the companies and letter signees, note that the struggle to develop antibiotics is largely due to the retail end of the equation. Most large pharma companies have abandoned antibiotic development due to the commercial challenges, they noted. The letter signers said antibiotics to treat these resistant infections are not only difficult to develop, but the “opportunities to recoup development costs and to make a return on investment are limited by the fact that, unlike many other types of drugs, antibiotics are generally used for a short duration.”

As an illustration of the financial issues, one of the companies that signed the letter, South San Francisco-based Achaogen filed for bankruptcy last month. Achaogen has been struggling financially despite securing regulatory approval for Zemdri (plazomicin) last year. Zemdri was approved in September as a treatment of complicated urinary tract infections that are caused by certain Enterobacteriaceae.

While Congress has enacted a number of programs in recent years to support the development of antibiotics, the drugmakers and other signers said the financing from those efforts is not sufficient. The group called for a post-approval pull-incentive package from Congress. Financial incentives would be paid to companies following antibiotic approval from the U.S. Food and Drug Administration in order to provide financial predictability for drug developers.

Since that letter was submitted to Congress in February, others have taken up the call for the government to create new incentives. Most recently, several speakers at the Milken Institute Global Conference took up the call for these incentives. Amitabh Chandra, director of health policy research at the Harvard Kennedy School of Government, told STAT News that the key to the issue will likely become a form of incentivization for the pharma industry. Such incentives could include additional years of exclusivity for a new antibiotic for a disease, Chandra said. In order to spur the development of these needed antibiotics, the speakers at the conference said the solution will undoubtedly be a public-private partnership of some kind, STAT reported.

Even as many of the larger companies have moved away from antibiotic development to focus on more lucrative products, such as in oncology, smaller companies have attempted to move into the space. Last fall, Qpex Biopharma, a company spun-out of The Medicines Company, launchedwith a focus on the development of anti-infective assets. The new company launched nearly one year after The Medicines Company announced the sale of its infectious disease business unitto Melinta Therapeutics.

Not only are there concerns about antibiotic-resistant bacteria, but there are also concerns about certain fungal infections that are resistant. Several companies, such as New Jersey-based SCYNEXIS and San Diego-based Cidara Therapeutics are in the thick of the fight to develop treatments for these concerns as well.

A sponsor chooses a site based on its ability to conduct the research, not on its financial management skills. But poor money management can sink a trial regardless of how well the site conducts the research.

In today’s budget-conscious environment, sponsors often contract with small- to medium-size sites that may not have the resources or expertise to effectively manage finances. And unless they provide their sites with the necessary support up front, chances are good that the sites will be overwhelmed.

“You’re asking someone who is doing a thousand other things [and] who might not have all of the accounting skills necessary, and you’re placing all of that responsibility on them,” says Christina Kahn, Senior Director, Site Alliance Management at Frenova Renal Research. “What happens is that thousands and thousands of dollars go unpaid,” Kahn says.

Most investigators in small- and medium-size sites don’t have the budget they need to hire support staff, including staff with expertise in accounting, points out April Mulroney, Senior Vice President of Accounting and Chief Data Officer at WCG Clinical. “Sites’ strong point is not accounting and finance but the research itself,” Mulroney explains.

Sponsors and CROs don’t always make it easy for sites, she says. “Sponsors don’t always provide the transparency on what payments are for, and sites will receive checks from the sponsor with a lump sum that often doesn’t reference the study or the reference period.”

Additionally, the fact that many sponsors wait 90 days or longer to reimburse sites can place researchers in a bind. “The financial burden this puts on sites is notable, since they’re having to pay their staff, their rent and their electricity all up front,” Mulroney notes. “In a sense, sites are fronting the industry on clinical research. It costs approximately $40,000 just to initiate a site, so if you’re not paying them on time, you’re not enabling them to succeed.” As a result, many sites drop out of clinical trial research.

“Payments to sites from sponsors can be unpredictable depending on the frequency of visits, frequency of source data verification from monitors and terms stipulated in the site’s contract,” says Greg Manning, Business Operations Manager at Suncoast Clinical Research. “If a site’s ability to operate is dependent on predictable revenue, then the site will need to build up a large operating balance in order to navigate through the leaner payment periods,” Manning says.

While a standard “recipe” for managing an organized clinical trial that hits its financial marks may be helpful, clinical trials vary in complexity and budget requirements. Standards must be tailored to the individual trial; however, studies often perform well when a finalized per-patient budget is established.

The per-patient budget, according to Manning, should align with electronic data capture (EDC) to produce payment. “You also need a mechanism to track revenue from visits, items that require invoices, and payments to patients, providers and vendors,” Manning adds. “This mechanism could be the source document or a visit checklist that is provided to accounting personnel.”

Clearing up payment worries also can increase sites’ research effectiveness, Mulroney says.

“Sites would be more focused on research if they didn’t have to spend hours trying to reconcile payments and figure out how much they’re owed,” she says. “They’re diverting their attention and their limited hours on areas that are not actually their sweet spot. Making payments timely is the number-one factor a site will consider when choosing which studies to initiate.”

Accounting technology also may help, Mulroney adds, yet investment in these technologies is tremendously low. “You would be shocked to see how many sponsors and CROs run their accounts payables to sites in an Excel spreadsheet,” she says. “The systems in place don’t talk to each other.” Some of the key systems that need to talk with each other, Mulroney adds, are the EDC, the system that generates the dollar amount that’s been contributed to the site, and a link into the banking system so payments can be made electronically and seamlessly.

Mulroney believes automation of accounts can be helpful, too. “A clinical trial management system should be integrated into [a site’s] activity system so that they’re auto-generating their receivables,” she says. “The whole process needs to be automated in addition to having a member or team that has expertise in accounting.”

According to David Scott, President & CEO of Palm Beach Research, if all sites adhered to strict financial and organizational standards, there would be greater growth of clinical trials because sites would be motivated to continue to pursue research. “Sites would be more equipped to financially survive,” Scott says. “Sites would also recruit more patients at a faster rate, and studies would turn over quicker. Research would only be limited by how quickly new treatment protocols are created by the scientists behind the pharmaceutical companies, not the failures of poorly prepared research organizations.”

“If all sites would efficiently manage their clinical trials by negotiating for fair and stronger budgets,” Manning says, “managing invoices and being transparent, then the industry could move to a more templated system where budgets represent a true fair market value from the beginning.”

“Sites would be reimbursed more efficiently and automatically, which would keep the focus on patient safety and protocol adherence without the need for complicated financial tracking.”

-By Brandon May

Clinical trials are carefully designed and monitored for research studies to test drugs, devices or procedures to find out if they are safe and effective before they can be approved for marketing and general public use.

Without a clinical trial, no new medicine or therapy can be approved for use and launched in the market. However, joining a clinical trial does not make one a guinea pig.

Each clinical trial uses specific criteria to determine if volunteers are eligible to participate. These criteria include specific factors, such as age, type of disease, medical history and current health. Depending on the study, participants may be healthy individuals or those with the particular illness being studied. Well-defined inclusion and exclusion criteria are put in place for every clinical trial to ensure that only eligible participants are chosen for the study.

Also, the participants in all phases of a clinical trial receive free medical consultation and medical care. Indian Good Clinical Practices Guidelines clearly state that payments should not be so large or the medical services so extensive so as to act as an inducement for a patient to take part in a study against their better judgement. All payments, reimbursement and medical services are approved by the Institutional Ethics Committee.

The goal of clinical research is to bring superior and life-saving medicines, new devices and medical technologies to patients in need. Safety of the study participants is the most critical component of clinical trials, and that is why there are laws, regulations and processes in place to protect trial volunteers at every step. Nations around the world establish and enforce rules for the ethical conduct of clinical research which ensures that patient safety is made a priority.

Patient safety is of utmost importance in any clinical trial. Clinical study protocols are developed to ensure that risks to study participants are minimized. These protocols are carefully reviewed by an Institutional Ethics Committee as well as country regulatory authority (Drugs Controller General of India) before a clinical trial can start.

– Indian Society for Clinical Research

Siro Clinpharm has announced a refresh of its core brand elements. Reflecting the growth and evolution of Siro as India’s leading CRO (Clinical research organisation), the brand elevates the focus on dependability, progressiveness, being scientific, and best in industry.

This brand refresh syncs with the next phase of Siro’s evolution. In this phase, Siro will focus on doubling the India team to 500 resources in three years, establish a strong operational presence in the US and invest heavily in technology and automation.

The new bold and vibrant logo in purple and lime green embodies the characteristics of the company’s committed team of employees. The colour is mainly used to convey credibility and evoke associations of quality, strength and steady determination. The logo employs an eye which symbolises an eye for detail, and an eye for humanity, resulting in the endeavour to achieve the highest standards in quality.

Akshay Daftary, Director, Siro Clinpharm said “We are excited for the brand refresh the company has undergone. Our refreshed logo and streamlined brand architecture convey the continuing evolution and growth of our business, and proudly display the characteristics we want to communicate to our stakeholders about our brands.

When it comes to offering to pay clinical trial subjects to participate, the line between compensation and coercion is difficult to draw but all too easy to cross.

Reimbursing participants for expenses incurred — travel, lodging, childcare — is a standard practice and clearly approved by the FDA. But the agency’s stand on incentive payments is not as clear, aside from a cautionary note in its Payment and Reimbursement to Research Subjects information sheet that advises IRBs to consider whether “proposed payment for participation could present an undue influence, thus interfering with the potential subjects’ ability to give voluntary informed consent.”

But one IRB expert says the consideration of influence as opposed to incentive should begin with the research team.

“Research teams have an obligation to implement an effective consent process, which includes ensuring that there are no undue inducements introduced into the process,” says David Borasky, vice president of IRB compliance for WIRB-Copernicus Group.

“When an IRB reviews a proposed study, it is only able to consider the population of potential subjects in the aggregate. The IRB cannot know how every potential participant might react to an incentive, and so it must approve research where the potential for an undue inducement has been minimized and rely on the research team to conduct an appropriate consent process.”

“I am not sure why it should be the IRB’s role to determine how individuals may want to use their time in order to receive a financial incentive, or why an IRB would believe it is in the best position to understand the impact at the level of the individual.”

Still, most IRBs are cautious about payments and may reject or reduce those that are “out of the norm.” The FDA advises IRBs to review both the amount of the incentive payment and the proposed method and timing of disbursement to assure that neither are coercive or present undue influence. For instance, payment should not be contingent on a participant’s completion of the trial. “Any credit for payment should accrue as the study progresses and not be contingent upon the subject completing the entire study,” the agency says.

But too much IRB involvement in setting payment amounts can hinder a trial. “There is nothing wrong with mere influence and demonstrating respect for persons by allowing individuals to decide for themselves,” Borasky says. “In fact, one could argue that if an IRB chooses to require a lower incentive, it is then making it impossible for a segment of the population to participate, because participation for some is not feasible without the presence of a financial incentive.”

“I don’t think there’s any doubt that lower-income individuals may be more attracted by a financial incentive compared to someone from a higher income bracket, but that does not mean it is automatically an undue influence,” he continued.

Paying for participation can also level the field among such disparate groups, says Susan Groth, associate professor at the University of Rochester School of Nursing.

“Use of financial incentives can enhance enrollment without undue coercion of any particular population and can serve as a means to equalize study participation,” says Groth, who served as a co-investigator on an NIH-funded study that explored the use of electronic technology to promote healthy pregnancies among women.

But the question of “reasonable” financial incentive can be challenging. Thinking in terms of risk in addition to time and effort, she explains, helps illustrate the difference between payment for services and compensation for a personal contribution. It’s important to demonstrate respect for what participants give — or give up — to take part in a clinical trial.

Around the world, the pharmaceutical market is rapidly evolving, driven by greater access to medicines, an increased focus on patient needs and the emergence of innovative therapies for chronic conditions such as diabetes, multiple sclerosis and rheumatoid arthritis.

Ulsan University Hospital (UHH) and Seoul National University Hospital (SNUH), Hepatology Division have joined the Novotech CRO partnership program

SYDNEY, Apr 18, 2019 – (ACN Newswire) – Novotech, the award-winning Asia-Pacific CRO with 23 years of experience in the region, has further strengthened its presence in South Korea with two major hospitals joining the Novotech partnership program – bringing more quality investigators, KOLs, and up to 4 million patients.

The 900 bed Ulsan University Hospital (UUH), and the Hepatology Division in Gastroenterology, Department of Internal Medicine at the 1,778 bed Seoul National University Hospital (SNUH), have joined the Novotech CRO partnership program, further strengthening Novotech’s clinical service capabilities in South Korea.

South Korea is a fast-growing destination for clinical studies with quality infrastructure, world-class medical and hospital facilities, and supportive rapid start-up regulations. South Korea was Asia’s most active country in clinical research after China last year, with over 400 sites opened by biopharma companies.

Novotech is well established in Asia with offices in 11 countries and more than 550 staff, while 19 leading hospitals and medical facilities across the region have now joined the Novotech CRO clinical partnership program.

Novotech CEO Dr John Moller said biotech clients were increasingly running Phase I studies in Australia, benefiting from the 41% R&D tax credit, then moving to Asia for subsequent trials. “Having the same company that understands the study as it transitions into Asia is always reassuring for clients. Novotech uses the latest Oracle and Medidata technology, so seamlessly connects with global clinical partners.”

About Novotech – https://novotech-cro.com/welcome
Headquartered in Sydney, Novotech is internationally recognized as the leading regional full-service contract research organization (CRO). With a focus on clinical monitoring, Novotech has been instrumental in the success of hundreds of Phase I – IV clinical trials across the Asia Pacific region.

Novotech provides clinical development services across all clinical trial phases and therapeutic areas including: feasibility assessments; ethics committee and regulatory submissions, data management, statistical analysis, medical monitoring, safety services, central lab services, report write-up to ICH requirements, project and vendor management.

Biologics offer new therapy options for numerous diseases: They are already used to treat cancer and autoimmune diseases such as rheumatoid arthritis as useful alternatives to standard therapies.

Pharm-Olam, a global, midsized CRO offering full-service clinical development solutions for oncology, infectious diseases and vaccines, and rare and orphan diseases, has been named a winner in Life Science Leader magazine’s 2019 CRO Leadership Awards.

Top U.S. academic centers are routinely ignoring federal rules requiring them to report clinical trial data, a new analysis by a pair of nonprofit advocacy groups finds.

Nearly one-third of the 450 university-based trials surveyed by Universities Allied for Essential Medicines (UAEM) and TranspariMED failed to report trial results within the 12-month window federal law allows.

“Only 15 out of the 40 universities assessed are in full compliance with U.S. trial disclosure law, while 25 universities are in violation of the law,” the groups say in a report issued last week.

There is gray area in the federal rules that require some, but not all, clinical trials to post results to the database ClinicalTrials.gov within a year of wrapping a trial. But the WHO has said that prompt reporting is a best practice. Failure to do so “is not a victimless crime,” UAEM and TranspariMED say in their report. “It has substantial negative consequences for patients, public health and access to medicines.”

In the UK, similar findings about unreported clinical trial data has led to parliamentary inquiries and even threats to drag university leaders before legislators to account for themselves. In addition to the U.S. and UK, European Union guidelines require drugmakers to post clinical trial data for any products registered with the EU.

The report’s naughty list includes some of the world’s most prestigious U.S. academic research institutions — MD Anderson Cancer Center left 23 percent of its trials unreported in 2017, the Mayo Clinic owed data on 58 percent of its trials, the University of California-San Francisco owed data on 63 percent of its trials and Columbia University owed 83 percent of its data, the report states.

Those four academic centers, plus the University of Chicago, accounted for half of the unreported trial results, Essential Medicines and TranspariMED say.

Adil Bharucha, director of Mayo’s clinical trials, said the clinic is “currently reviewing” its case files “and will do whatever is necessary to close the loop.”

“Mayo Clinic makes every effort to be compliant with FDA clinical trial transparency requirements. We recognize the importance of sharing results with our patients and public and take this seriously,” Bharucha said.

The report also makes note of universities that have “put significant effort” into catching up with their reporting obligations, including Indiana University, University of North Carolina-Chapel Hill, University of Rochester, University of Pittsburgh and Yale, which all have cleared more than 85 percent of their backlogs as of February 2019.

To keep track of their data tracking responsibilities in the future, UAEM and TranspariMED recommend universities accept and implement the WHO standards for data transparency and commit to posting results within 12 months of trial completion for all trials, not just those required by U.S. law.

Read the group’s report here: https://bit.ly/2U33KWh.