The Dark Side of Drug Trials !!!

Drug testing in clinical trials has always involved a kind of moral trade-off—subjects are asked to take risks for the greater good.But in an age when consumerism has infiltrated medicine, regulatory protections for the so-called guinea pigs who volunteer for trials are flimsy at best, with inadequate accounting of the deaths and injuries to test subjects.

So says physician and author Carl Elliott, a professor at the Center for Bioethics at the University of Minnesota, who recently delivered the second annual Cathy Shine Lecture at the School of Public Health. Sponsored by the health law, bioethics, and human rights department, the lecture is endowed by the family of the late Cathy Shine, a strong advocate for human rights who died in 1992 from a severe asthma attack, in recognition of the scholarly work of George Annas, a William Fairfield Warren Distinguished Professor and department chair. Annas wrote about the Shine case and the importance of respecting patients’ rights in a much-cited article in the New England Journal of Medicine.

Elliott’s talk, titled The Dark Side of Research: Exploitation in Clinical Trials, drew from his controversial book, White Coat, Black Hat: Adventures on the Dark Side of Medicine.

“Many of these trials—especially Phase I clinical trials, which are early-stage studies done primarily to determine whether a drug is safe—exploit impoverished, vulnerable people, especially the mentally ill,” says Elliott (left). “Few people realize how little oversight the federal government provides for the protection of subjects in privately sponsored studies.”

At a time when industry ties to physicians are facing increasing scrutiny, Elliott has written and lectured extensively on the influence of the pharmaceutical industry in medicine. Federal health care reform legislation calls for drug companies to disclose, by September 2013, all payments to doctors for consulting, speaking, gifts, and meals. Research funded by Big Pharma has drawn increasing criticism.Elliott is one of a corps of physicians nationally who have publicly questioned the ties between medicine and industry, ties that he believes will take years to sever.

He has taken on drug companies and universities in making his case against industry manipulation of clinical trials—including his own employer, the University of Minnesota, which participated in a controversial drug trial during which a 26-year-old man committed suicide. Although the university was exonerated in the case, Elliott publicly questioned its decision-making in a 2010 Mother Jones article and again inWhite Coat, Black Hat, published the same year.Elliott has written or edited seven books, including A Philosophical Disease: Bioethics, Culture and Identity (1999) and Better Than Well: American Medicine Meets the American Dream (2003).

He spoke with Bostonia about his qualms and his conclusions:

Bostonia: You write about lack of oversight of clinical trials and the vulnerability of the “guinea pigs” paid to participate. What’s the main problem with the drug-testing system?

Elliott: The main problem is the profit motive. Drug research has become an almost completely commercial enterprise. It’s funded by the drug industry; it’s managed by CROs (contract research organizations); it’s carried out in for-profit testing sites. It’s done by doctors in private practice, and it’s approved by commercial ethics boards—each of which operates as a private, commercial, for-profit enterprise. Yet it is not regulated as a commercial enterprise, so there are abuses.

What should a patient know before participating in a clinical trial?

Way too many things to be listed here. One thing that patients ought to know, but are never told, is how much money the investigator is getting for the trial—especially how much money per research subject.

Your book uses the image of doctors in black hats. Did the pharmaceutical companies put those hats on physicians, or are other culprits involved?

I think a lot of physicians were eagerly shopping for the black hats themselves.

In the last few years, 12 drug companies have publicly disclosed payments—from meals to speaking fees—to physicians, either voluntarily, or not. Do you think public disclosure will make a difference?

Initially, I was skeptical, because in academic medicine, working for Pharma is often seen as a mark of pride, not shame. But I am changing my mind. One great thing that has come from the Dollars for Docs database that the news organization ProPublica compiled—which lists payments to physicians—is to make it much easier for investigative reporters to look into possible cases of corruption. So disclosure is a good step.

Do you think banning all industry gifts to doctors makes for better medicine?

Yes, because it would put us all a step closer to a situation where a doctor’s decisions are based on scientific evidence and sound clinical judgment, not industry spin.

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Clinical Trials

Clinical research with human participants utilizes a systematic approach to help understand human health and illness in order to find safe and effective ways to prevent, diagnose, and treat disease.Most clinical research in the United States is sponsored by pharmaceutical or biotechnology companies, which spent more than $10 billion on it in 2002; the U.S. National Institutes of Health is the second largest sponsor. Clinical research has a long history and has resulted in significant benefits for society, yet it continues to pose profound ethical questions.Clinical research involves clinical trials, which are designed to test the safety and efficacy of interventions in humans. Carefully conducted clinical trials of treatments, prevention modalities,medical devices, and other interventions are considered the fastest, safest, and best way to determine whether they work for cancer, HIV/AIDS, asthma, and many other diseases. Treatment trials test experimental treatments, new combinations of drugs,or new approaches to surgery or radiation therapy. Prevention trials test medicines, vaccines, vitamins, or lifestyle changes to see if they can prevent disease or disease recurrence. There are ethical concerns about clinical trials because some individuals are asked to accept a burden or risk in order for researchers to develop knowledge that will benefit others.

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What Is Patient-Centricity?

What Is Patient-Centricity?

 By Norman M. Goldfarb 

The recent CHI Summit for Clinical Ops Executives (SCOPE) conference in Miami offered almost 1,300 attendees from pharmas, biotechs, CROs and other service providers numerous sessions on patient-centricity and a broad range of other topics. Most clinical research professionals would probably agree that patient-centricity is very important, but we lack a common understanding of the term. This article will propose a definition for patient-centricity and identify characteristics that make a clinical study patient-centric. Defining “Patient-Centricity” The first principle in defining patient-centricity is that the term itself should be patientcentric. In other words, when patients read the definition, they should agree with it from their perspective. Patient-centricity is not about our goal of recruiting more patients for clinical studies — it’s about their goals when they participate in a clinical study. It is not about our methods for communicating information to patients — it’s about their preferences for obtaining information. Since different patients have different goals, concerns and preferences, the second principle of patient-centricity is that it must be specific to each individual patient, or at least each group of patients with like characteristics. Patient-centric studies provide a personalized experience for each study participant. The third principle of patient-centricity is that it begins when a study is contemplated and ends when the patient’s experience is complete. The fourth principle of patient-centricity is that is applies when a person is a patient, when he or she becomes a study participant, and when he or she returns to being a patient. (In this article, the terms “patient” and “participant” will be used interchangeably.) Based on these principles, we can now propose a definition of patient-centricity: A clinical study is patient-centric when, from each study participant’s perspective, it achieves his or her goals in a manner sensitive to his or her individual concerns and preferences, over the entire life cycle of the study. Although it has not been proven empirically, patient-centricity should also help achieve the study sponsor’s goals. 

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CTMS Procurement: The Seven Deadly Sins

Malcolm Weaver

Keywords: Clinical Trial Management System (CTMS)

Clinical trials are becoming larger, more expensive and increasingly complex. Numerous factors conspire to drive this increase in size, cost and complexity including increased regulatory scrutiny; submissions in greater numbers of markets; a greater proportion of investigational drugs targeted at chronic diseases; and, in some therapeutic areas at least, competition for patients and investigators. Effective management of clinical trials is, therefore, critical for pharmaceutical and biotechnology companies worldwide. In response, vendors have produced a number of IT solutions allowing sponsors, Clinical Research Organisations (CROs) and investigators to run clinical trials more effectively and efficiently. Many clinical trials now employ clinical data management systems (CDMS), clinical trial management systems (CTMS), electronic data capture (EDC), drug supply management (DSM), and interactive voice response systems (IVRS).

CTMS, for example, helps improve trial management processes and better manage costs. Cost management is a particular priority for pharmaceutical and biotechnology companies aiming to maximise their return on investment or minimise the financial burn. It is estimated that keeping a trial running costs around US$40,000 per day. The impact on lost sales revenue is even more marked: every extra day that a drug remains in clinical studies costs the sponsor at least US$600,000 in lost sales. Apart from making it easier for sponsors to attain key clinical trial milestones and helping to control costs, CTMS also offers intangible benefits, such as improved regulatory compliance, reduced complexity, superior information flow and enhanced relationships with clinical investigators.
Several CTMS solutions are available commercially, and the most appropriate choice depends on numerous internal and external factors, many of which are company-specific. However, the author has identified seven ‘deadly procurement sins’ surrounding CTMS. Executives that fail to consider these issues could find that the CTMS does not meet their needs and does not optimise the benefits that the technology could offer their organisation. This article will begin, however, by briefly considering the benefits of CTMS.

The benefits of CTMS
CTMS offers the opportunity to track, measure and report on virtually every aspect of a clinical trial or study program. The relational database at the heart of the CTMS groups, analyses and filters information at various levels including, among others, trial, country, site, investigator, product, clinical research associate (CRA) etc. As a result, a CTMS provides a view of trial management data suited to a variety of individuals within the organisation, including high-level, consolidated metrics for senior managers. The CTMS allows managers to view the progress of several studies and compare approaches in order to optimise future studies. Financial managers can view the total costs and expenditures across clinical programs. The CTMS can also provide detailed reports allowing, for example, a project manager to view enrolment figures for a specific site or investigator and assess the performance of the study recruitment strategy to respond in a timely manner by opening new study sites or taking other actions to ensure target timelines can be met.
Against this background, the CTMS offers five main benefits:
l Companies can track and obtain reports on every aspect of day-to-day trial management. This enhances operational and project management control. Moreover, the CTMS allows managers to deploy monitoring resources in the most appropriate manner to address a particular issue.
l The CTMS delivers relevant information to study stakeholders as rapidly as possible. This helps to manage the relationship between CRO and sponsor as well as enhancing operational control of individual studies and the entire program.
l The CTMS helps sponsors promote operational and workflow standards. CTMS standardises processes across all project teams and increases efficiency, by sharing common data across clinical studies.
l The CTMS can ensure timely investigator payments and allow accurate financial reporting. Timely payments help maintain investigators’ interest in and commitment to the study.
l The CTMS should import data from and export data to other key technologies, such as IVR, EDC and CDMS solutions. Once again, this helps reduce the risk of data entry errors and facilitates the timely completion of the clinical study.
Most vendors offer configuration and customisation options to allow a company to configure a CTMS to meet its specific needs. Beyond these common attributes, the various CTMS differ in several ways. As a result, to ensure that investment in a CTMS is maximised, executives with procurement responsibilities should avoid these seven ‘deadly sins’.
Deadly sin #1: Using old technology
It’s a truism that technology dates rapidly. Therefore, to make the most of the functionality and utility offered by a CTMS (as well as to future-proof the system) the interface and relational databases need to be up-to-date and employ new technologies. Despite this, some CTMS still use technology introduced some 15 years ago. This use of older technology can lead to several problems:
l Installing CTMS based on older technology can be protracted. It can take three days just to load the program from CD-ROMs to the database server.
l Relatively few people have the experience to program and trouble-shoot older software systems. This may be a particular issue in smaller companies.
l Many Windows-based techniques that we use almost instinctively, such as the right mouse click, are not available with the older systems. Using newer systems, users can navigate rapidly, promoting consistent and efficient work processes. An increasing number of studies are performed in non-traditional countries, such as Central and Eastern Europe, Asia and Latin America. Web-based systems, such as TrialWorks® by ClinPhone, IMPACT™, and globalTRIALS™ have a distinct advantage in these studies. The program does not need installation on the user’s PC, which can give substantial savings in terms of PC support. Moreover, web-based systems allow the instant implementation of software updates.
Deadly sin #2: Protracted implementation
Some CTMS applications can be slow to implement. As mentioned above, systems based on older software can take three days to load the program from CD-ROM to the database server. For newer solutions, installation typically takes place in a matter of days. Further, the easy-to-use user interface of modern CTMS, means that clients can begin using these solutions within a few days of installation. With trials often costing tens of thousands of dollars a day, getting the system up and running rapidly is a commercial priority.
Deadly sin #3: Insufficient reporting capability
The ability to access a diverse range of reports tailored to the specific needs of multiple users is the raison d’être for a CTMS. Therefore, the CTMS should offer a vast suite of standard reports, as well as ad hoc reporting, enabling users to quickly access the consolidated information they require. Using systems based on older technology, writing a report can take a day, compared to minutes with newer systems.
Deadly sin #4: No remote monitoring module
Remote monitoring modules offer a valuable tool for mobile CRAs. Before a site visit, the CRA downloads the relevant data they need onto their laptops. During the site visit, the CRA updates the data in the remote monitoring module; this data is then used to create monitoring visit reports and other documentation, and is uploaded to the central database where it is available to other CTMS users. Using a remote monitoring tool is more efficient than employing paper-based systems and, in particular, reduces the risk of errors. This optimises the use of CRA time. Remote monitoring tools are especially valuable when the sponsor uses multiple CROs. The standardised system avoids complications that can arise from different CROs using different management software.
Deadly sin #5: Not working with other key technologies
The CTMS should work with the other IT solutions that are now commonplace in clinical trials. For example, IVR is widely used for randomisation, management of trial supplies and collection of patient diaries. The CTMS should offer two-way, real-time integration with IVR. In this way, for example, the IVRS automatically enters patient enrollment and visit information into the CTMS, providing an accurate and continually updated picture of patient recruitment and progress within the CTMS. Indeed, the CTMS should be able to import relevant information from virtually any IVR, EDC or data management system. This increases the currency of essential tracking and performance data contained within the CTMS, facilitating timely management reports and decisions.
Procurement executives should consider the benefits of being able to export data to Microsoft Word, Outlook, Project, Excel and email/calendaring software, as well as other productivity tools, such as FedEx shipping software. They should also consider including the abilities to hyperlink to study templates, documents and folders; to create XML files for upload to www.clinicaltrials.gov; and to automatically generate check requests. Finally, integrating patient visits with payment data to ensure investigator payment is generated quickly. Rapid payments help establish a good relationships with investigators and their sites.
Deadly sin #6: No hosted solution
Many CTMS companies do not offer a hosted solution. Unfortunately, many smaller clients cannot call on the large IT infrastructure common in larger companies. In other cases, larger companies prefer to outsource IT support in order to focus on their core competencies. As a result, procurement executives need to consider the benefits of licensing and installing the CTMS on-site compared to implementing a hosted solution. In hosted solutions, third-party companies act as an IT department and provide unlimited technical support. The software resides at the host’s facilities, which users access over the internet. The hosting environments are secure and include 24/7 network engineering support, redundant power supplies, redundant internet connectivity and scheduled backups.

Deadly sin #7: Hidden costs
In some ways, the system’s price is the least important of the seven deadly sins. The cost itself is probably less important than the value it represents. Prices for a CTMS can vary from $50,000 to several million dollars. There is often the perception that the higher the price, the better the product. However, in the case of modern CTMS solutions, the very features that make them easy to use and rapid to implement, also lend themselves to rapid development lifecycles, and hence lower license costs.
Executives also need to consider the license structure. Many solutions only offer licenses based on named users, which is inflexible in the current model of clinical research, where companies frequently redeploy resources to maximise efficiency and the use of CROs is prevalent. By comparison, the concurrent user licence model gives companies complete flexibility in how to deploy internal resources and use external ones.
Moreover, using a system with an intuitive and user-friendly interface minimises user training, increases user efficiency and requires less user support. Intuitive systems also facilitate use by third parties or infrequent users with minimal training. These factors all contribute to reducing the overall cost of implementation and ongoing support for the lifetime of the product.
In conclusion, a CTMS makes managing clinical trials easier, faster and more efficient. The choice of vendor and system depends on balancing various and sometimes competing factors. Nevertheless, considering the seven potentially deadly sins outlined above allows companies to procure the most cost-effective and efficient CTMS to meet their needs, maximises the return on investment and helps get the company’s drugs to market as rapidly as possible.

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((Malcolm Weaver (info@clinicaltrialsoftware.com) is Business Development Manager, ClinPhone Group Limited. To comment on this article, email comment@crfocus.org. Comments might be published on the Clinical Research focus web pages, with author’s name/affiliation, unless notified otherwise)).

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Guidelines to write an effective abstract

by Gitanjali Martha

The abstract, which is a concise portrayal of the research work, is a decisive factor for the target journal or reader. It is not only essential to encourage people to read your paper, but also to persuade them to cite it in their research work. Thus, it is worth investing some extra time to write an attractive yet simple abstract.

First, it is important to read the main text several times to mentally absorb and retain the whole research work. Thereafter, attempt a draft that does not merely copy the sentences from the main text of the paper. Instead, the abstract should encapsulate the research concisely. Going through several iterations is a good way of improving an abstract.

The first few sentences of the abstract should illustrate the background and the purpose of the research work. These sentences should grab the reader’s attention and create an inquisitiveness to read in greater depth. The next couple of sentences should focus on the methodology of the research. Finally, the abstract should end with the result and conclusion part, which should be summarized in just 3-5 sentences. This part should be concise and emphasize the significant results and not the statistics.

Once the draft is done, proofread the draft to refine it as much as possible. Avoid verbose writing and verify the text for coherence of the information provided and proper usage of grammar. Besides text, scientific journals have come up with a new idea of summarizing their research paper through a graphical abstract. A graphical abstract is a single, concise, pictorial and visual summary of the main findings of the article. It could either be the concluding figure from the article or a figure that captures the content of the article for readers at a single glance. These days, researchers and scientists find abstract writing to be a cumbersome process and instead opt for a graphical abstract.

Regardless of the type of the abstract, it is an essential part of your manuscript that persuades editors, reviewers, and other researchers to absorb your research in detail.

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Effective Peer Reviewing

by Sushree Shailani Suman

What do you mean by “Peer Reviewing”?

A peer review is a planned and well-organized process that aims to improve the quality of a research paper. It is the most effective feedback-generation system that takes place during the development of a research paper.

Who is considered as a “peer”?

A peer is someone who is related to the field of study, doing similar kind of research, and an expert in the mentioned area of research. A peer is neither the author nor the person who has provided grants for successful completion of the research paper.

Types of Peer Review:

In broader terms, peer reviews are classified into two types: internal peer review (which includes the editorial team members) and external peer review (which includes experts in the particular field of study).

The peer review process looks for:

• Suitability of the paper for the target journal, which may include cross checking with the journal requirements and scope of publication of the research article. The reviewer’s objective is to identify the uniqueness of the conducted study.
• Relevance of the intext citations as well as those in the reference section.
• Accuracy of the statistical analysis and correct presentation of the data.
• Proper and accurate formatting of the text, tables, figures, references, etc.
• Confirmation of the inclusion of the conflict of interest disclosure, copyright forms duly signed by the authors, citation of the ethical consideration, etc.
• Relevant citation in the conclusion.

There are several advantages of peer reviewing. The process:

• Leads to the generation of a high-quality publication by improving the contents.
• Helps in the improvement of the structure of the paper.
• Provides a logical view of the research paper.
• Enables the author to use critical feedback in a productive or constructive manner by incorporating important changes in the research paper.
• Helps authors by pointing out the strengths and weaknesses of the research work.
• Helps authors in their learning process for future research.

Conversely, an inadequate or below-par peer review might lead to the following problems:

• Poor error and fraud detection.
• Slower process for finalizing the paper.

Nonetheless, the advantages far outweigh the cons. Therefore, the peer review process needs to be adopted by research writers as it helps them improve the quality of the research writing.

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Scientific Review of Human Subjects Research

By David B. Resnik

One of the key principles of ethical research involving human subjects is that it should be   scientifically rigorous (Levine 1988, Emanuel et al 2000). Scientific validity is important so   that research studies will not unnecessarily expose human subjects to risks (Emanuel et al   2000). Research should address important scientific questions.   Regulations and guidelines require that the research risks be reasonable in relation to the   benefits to the subjects or to society by means of the knowledge that is expected to be   gained (Emanuel et al 2000). If a study is unlikely to produce useful scientific results, there   is no acceptable level of risk to the subjects (Council for the International Organisations of   Medical Sciences 2002).   A poorly designed study might fail to yield useful knowledge, which undermines the ethical   justification for exposing human subjects to risks. For example, in 2001, Ellen Roche, a   healthy volunteer, died from inhaling hexamethonium as part of an asthma study conducted   at Johns Hopkins University. An investigation of this tragedy by the Office of Human   Research Protections found that the researchers had not adequately reviewed previous   research on the dangers of inhaling this drug, published in the 1950s and 1960s (Savulescu   and Spriggs 2002). In other words, the study was not ethically justifiable because the   scientific literature indicated that the research design did not include adequate safeguards   to protect subjects from the risks associated with inhaling hexamethonium

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Five Steps for Improving Processes in Clinical Trials

By John R. Wilson, Jr.

Nobody would accuse the clinical research enterprise of being a paragon of efficient processes. It’s not that we don’t want our processes to be efficient; it’s just that the work needs to get done, no matter how inefficient the current processes are. After an initial burst of enthusiasm, process improvement projects seem to lose steam and then are quietly set aside for more pressing priorities.
The good news is that there is a proven, five-step process for improving business processes.
This article will provide an introduction to the five steps, using risk-based monitoring (RBM) as an illustrative example.But first, let’s define what we mean by “process.” In essence, a process is a standardized series of steps taken to achieve a goal. Processes simplify, streamline and regulate our activities. Formal processes are known as procedures (“standard operating procedures (SOPs)”), with well-documented steps. In our business, procedures are frequently designed to comply with governmental regulations and guidelines. Informal processes, on the other hand, just seem to exist as customary practices that are passed along by word of mouth,
along with the forms and other artifacts of the process.
The Japanese method of kaizen (continuous improvement) is not limited to incremental changes. Sometimes, major changes are required to fix an obsolete or broken process. RBM, for example, requires major changes that cannot be implemented in tiny steps.Successful organizations must therefore be able to make major process improvements.
The five basic steps to significantly improve a process are: (1) map, (2) analyze, (3) redesign, (4) assign resources, and (5) implement improvements. Only after completing the first four steps can we productively move on to the fifth step, in which a process is actually improved

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rend sees patients paying for their own clinical trials, but critics raise ethical concerns

As a bio-sciences start-up, Regenastem Inc. is beginning life in typically modest fashion. It has secured lab space at an incubator run by a small Ontario university, its website is rudimentary — and it has tapped into a surprising source to pay for two new clinical trials.The studies of cell-based arthritis and spine treatments — conducted with a Buffalo, N.Y., research company — are to be funded by the patients who take part in them.The firms are part of an intriguing — and controversial — new trend. Unable to access research dollars from governments, health charities or pharmaceutical companies, many developers of new treatments are turning to the people who want to participate in their studies for financial support.So-called “pay-to-participate” clinical trials have helped launch investigations of everything from impotence treatments to multiple sclerosis medication.

The stem-cell therapy hockey legend Gordie Howe underwent in Mexico triggered intense media attention earlier this year. What was largely overlooked is that Howe was part of a trial that charged other stroke patients $32,000 to join.“It’s a model of funding that I think we are going to see being proposed more and more in the coming years,” said Jonathan Kimmelman, a McGill University bio-ethicist.Patients are paying to be part of trials primarily of cutting-edge stem-cell and other cell-based treatments — relatively inexpensive for small players to develop — and therapies for rare diseases that get little attention from industry, he said.But the idea is triggering debate.Critics, including Kimmelman and colleagues in a new journal article, warn that such studies are rife with ethical problems that could harm patients and produce questionable science.

People who pay to be part of a study will naturally be unwilling to take the chance of receiving a placebo, the McGill professor said. And yet having a placebo “control” group and blinding patients and doctors to who is in which group is key to obtaining the most reliable data, said Kimmelman.Some patient-funded studies appear not to even be true research, but more a way to market unproven treatments, he said.“It’s co-opting the kind of scientific aura that we associate with clinical trials,” Kimmelman said. “(But) if your business model is to sell the trial itself, as opposed to the product, you don’t have strong incentives to design rigorous clinical trials.”Proponents respond that patient fees, though unconventional, make possible research that might otherwise never get off the ground.

If your business model is to sell the trial itself, as opposed to the product, you don’t have strong incentives to design rigorous clinical trials

“As funding becomes harder and harder to secure for all the good work that legitimate clinical trials seek to accomplish, society needs to be open to this evolving creative process,” said Dave McGuigan, vice president of San Diego’s Stemedica, the company whose treatment was administered to Howe.Patient-funded trials can also plug a gap that major pharmaceutical companies are unwilling to fill, testing stem cells and other products that are difficult to patent — and therefore unlikely to attract huge sums of money for traditional testing, said Rafael Carrillo, head of Stemedica’s Mexican partner, Novastem.

Even Kimmelman says he is not completely opposed, and in a paper coauthored with two American colleagues, proposes a series of measures to make the idea ethically workable, chiefly by requiring regulatory oversight.Finding money to run trials — the priciest part of medical research — has always been a challenge, and budgets for government funding bodies like the Canadian Institute for Health Research have generally been declining in real dollars.

In that demanding environment, there are now “numerous” trials around the world financed either entirely or partly by patients, said McGuigan.That includes 14 being run by Novastem, like the study of the stem-cell treatment for stroke survivors that Howe’s family claims had a dramatic effect on the NHL luminary. But the company is also helping fund those trials, McGuigan stressed, under a model he calls patient-assisted.

“Patient-assisted clinical trials — where all parties bear a portion of the financial risk — are an ideal way for society to advance clinical trial initiatives … when no other external financial resources are available,” he said.Patient-supported research is often not double-blind and controlled because “you can’t ask a person to pay an important amount of money” and give them a placebo, said Carrillo. But if the results are promising, they could lead to more scientifically rigorous clinical trials, he said.

Meanwhile, U.S. law specifically allows for patient-funded studies in certain circumstances.

A Florida company called Ageless Regenerative Institute has Food and Drug Administration (FDA) approval, for instance, to look at treating erectile dysfunction with stem cells derived from body fat. The trial is “patient-sponsored.”Regenastem, based at Brock University’s Biolinc facility in St. Catharines, says it has developed what it calls its own “unique” way to isolate stem cells from adipose — fat — tissue.It is working with the Buffalo Research Group to set up two trials that involve removing cells and blood from patients’ bodies, processing them and injecting them back to treat arthritis and disc-related pain.

Patients – all of whom are to receive the treatment – will be charged $7,500 each, which only just covers costs, and enables doctors to provide good care while also gathering scientific data, said Jason Kane, the company’s CEO.The process has been endorsed by Brock, the treatment itself is already approved in Australia, he said. Without patient funding, Regenastem “would not be able to finance a study of any size.”McGill’s Kimmelman, however, worries about more than just the scientific value of pay-for-participation studies, arguing the subjects’ own best interests may be at risk.

Experimental treatments are usually studied on as few people as possible until safety is assured. But when the subjects fund the study, there is financial incentive to enroll numerous patients, exposing more people than necessary — and possibly unsuitable ones — to possible harmful side effects, he warned.“This can tarnish a reputation of a new and emerging research area,” he warned. “There is some threat to actually undermining the progress in certain areas.”

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source:National Post

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Is There Too Much Risk in Clinical Trials?

by Tom Groves

Mention the word ‘risk’ to any patient participating in a clinical trial and it will bring up ideas of alarming side effects, the issues experienced with TGN1412 at Northwick Park in 2006 or the thalidomide experience of the 1950s and 1960s.  Mention the word ‘risk’ to monitors and CRAs working in clinical trials and that will bring up the idea of ‘Risk Based Monitoring’. Mention the word ‘risk’ to a Clinical Project Manager and this will bring up the ideas of the trial going over budget, the trial not delivering on time, the investigational drug being placed on clinical hold, resource limitations etc. The simple fact is that the word ‘risk’ means different things to different people. This can have far reaching consequences if different groups of people have a different interpretation of the same word.

So what actually is risk?

Well that is exactly the question that needs to be addressed. The definition of risk is “The possibility that something unpleasant or unwelcome will happen”.  The term “possibility” means that it may or may not happen, it certainly does not mean it WILL happen or has already happened.  If something has already happened then this is no longer a risk but instead it becomes an “issue”.  The terms “unpleasant” or “unwelcome” highlight the fact that with risks we are looking at have a negative effect. The opposite of the term “risk” is opportunity. An opportunity is the possibility of a better than expected event, for example the possibility of recruitment being completed well ahead of schedule.

Types of “Risk” in Clinical Trials

There are many classification systems for risk.  Many of these have been related to specific classifications of trials, e.g. commercial vs non-commercial.  I am not attempting here to provide a summary or overview of these and equally not looking to critically appraise these. Instead, I am attempting to provide a framework for the considerations of risks in clinical trials and to try to move away from the use of a single word of “risk”

Risks to Patient

• Safety related to investigational product, medical device and comparators used in the trial
• Safety related to specific procedures and assessments used in the clinical trial
• Failure to protect personal data

Risks to Sponsor

• Failure to obtain desired outcome from the trial (i.e. inconclusive/negative outcome)
• Exceed/run-out-of funding
• Late delivery of results of trial
• Integrity of data and/or results

Risks to the Healthcare Market

• Incorrect/unreliable results from trial
• Patients being enrolled in sub-standard clinical trials rather than being included in trials of a greater scientific value
• Resource usage reviewing trial results that are of little value

There are obviously a multitude of risk reduction techniques that can be applied to the above risks, many of which are the result of an increased financial investment in the trial, e.g. more time and scientific input to the design of the trial, larger patient population, 100% SDV and data validation.

The many people the term “Risk Based Monitoring” is the buzz-word of the moment.  Whether this is actually a risk reduction technique is questionable. Perhaps this is more of a ‘focus on the important’ approach to monitoring to increase the efficiency of resources without

compromising the quality of the trial and the trial results.  In the same sense as “Risk Based Monitoring” should we also be seeing the terms “Risk Based Data Management”, “Risk Based Statistical Analysis”, “Risk Based Protocol Design” being used more often?

In 2011 the Department of Health, Medical Research Council (MRC) and the Medicines and Healthcare Products Regulatory Agency (MHRA) published a paper entitled “Risk-adapted Approaches to the Management of Clinical Trials of Investigational Products”. This is a framework for the managing trials based on different levels of risk and these risks cover many of the areas discussed above.  Risk-adapted monitoring is just a part of this framework.  In essence the framework looks at determining the level of “risk” there is to the patient and the importance and impact of the trial result. Once these have been determined the design and management of the trial can be done to the required levels so as to address the risk. FDA also recently finalised their guidance on risk based monitoring which focuses mainly on monitoring but also mentions other aspects of trial management.  Neither document however, looks specifically at the delivery aspect of the trial, e.g. time and money, which are the some of the risks to the sponsor.

So what are the risks in clinical trials?

Patient Safety & Reliability of Results Risks

These are the risks that can be addressed through Risk-Based and Risk-Adapted approaches to clinical trials. Determine the level of risk and then design and conduct a trial to an acceptable level.  I would refer to these as Risk associated and addressed through Design, Conduct & Analysis

Delivery of the Trial to Cost & Time

These are the risks to the sponsor of time and budget over-runs. In some cases these can have major consequences (time to market, first to market, providing safety updates following approval). I would refer to these as Delivery Risks.

This therefore leaves one question. Who manages which category of risk? This is not a simple question to answer. Unless the different kinds of risk are understood, categorised and assessed from the beginning then the risks will not be managed. Patient Safety and to some extent the reliability of results have always been risk assessed as Ethics, Regulatory Authorities and Protocol Review Committees will review clinical trial protocols to ensure that these aspects are met.  The Delivery to cost and time are often a more challenging set of risks to a clinical project manager for many reasons including lack of PM experience, focus on the scientific and monitoring aspects of trials through to lack of visibility and management tools.  Failure to address risks prospectively frequently leads to the project manager dealing with “managing issues” relating to delivery, whilst ironically at the same time probably leading a project deploying “risk based monitoring”.

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