New NIH Website Aims to Make Global Clinical Trials Easier

December 18th, 2014

global clinical trialsA new National Institutes of Health website aims to make it easier for clinical trials around the world to comply with relevant regulations. Recently launched by NIH’s National Institute for Allergy and Infectious Diseases (NIAID), the new ClinRegs website is intended to assist clinical researchers by providing them a database showing the specifics of each country’s rules on clinical research.

Officials at the NAIAD say the website can serve as a central resource for international regulatory issues, which should save time and streamline compliance efforts for clinical trial planners. In fact, project officials said the website was developed after finding that regulatory compliance was a frequent, common hurdle for researchers and sponsors trying to plan clinical trials.

At the time the beta version of ClinRegs was launched in early September, it included clinical trial rules in 12 of the most active nations in clinical research (besides the US, the UK, China and India, these also include Brazil, Kenya, Malawi, Peru, South Africa, Tanzania, Thailand and Uganda).

NIH officials say more nations will be added in the future. Before the end of this year, regulatory information is expected to be added for Sierra Leone and Liberia, likely sites for clinical research on Ebola fever vaccine and remedies. The number of countries covered by the new website is anticipated to more than double over the next three to five years. Haiti, Mexico and Vietnam are among likely additions in the near future.

The new website displays information on seven key clinical trial regulatory topics – the national regulatory agencies (including links to the national authority), oversight of ethical committees, clinical trial approval and management, research sponsorship, informed consent of trial participants, and rules on biospecimens and investigational products.

In what the agency touts as a particularly useful feature, ClinRegs also allows users to bring up side-by-side comparisons of any two nations in the database.

NIH says the website’s summary of each nation’s clinical research regulations will be reviewed at least annually, and more frequently if it finds major regulatory revisions or additions. The date of last revision will be shown on the website. The ClinRegs team says it hopes to attract input from research and regulatory professionals worldwide, to keep its information current and accurate.

While ClinRegs is primarily intended to aid individuals and organizations involved in planning, conducting and overseeing clinical research, it is also open to members of the public, and the input of all users is being sought.

Visitors to the website are greeted by a short pop-up survey, in which NIH asks how often they visit the site, how they found it, their purpose in visiting, and specific research topic. The survey also asks visitors to rate the site’s design, helpfulness, and ease of use, and to identify additional countries they would like to see added to ClinRegs.

NIH also invites further comments and suggestions for improvements to be sent to: NIH, Project Clearance Branch, 6705 Rockledge Drive, MSC 7974, Bethesda, MD 20892-7974, ATTN: PRA# 0925-0668.

“Big Data” Analysis May Aid Selection in Clinical Trials and Aid Treatment Decisions

December 4th, 2014

clinical trials for patientsThe growing ability of scientists to analyze ever-increasing mountains of health data has drawn increased attention to clinical research uses of “big data.”

While public and private efforts to sequence human genetics took over a decade and cost $3 billion, today analyzing an individual’s genetic makeup takes one week and costs $1,000. As data volume and analytical tool sophistication grow, clinical researchers – supported by research centers and agencies — are increasingly drawing on larger, more diverse data sources.

The National Institutes of Health, for example, in 2012 launched an agency-wide Big Data to Knowledge initiative, and last year committed $100 million to BD2K research; NIH wants to see big data more standardized and widely used and shared. Proliferating electronic medical record systems offer broader data on larger groups.

Big data not only lets trial enrollers cast a wider recruitment net, but also find genetic or other factors affecting susceptibility to the disease or therapies, thus identifying enrollees more likely to benefit and less likely to suffer side-effects which might drive them out of trials. Access to wider databases can also help spot new correlations, such as previously unsuspected drug interactions.

A recent article in the New York Times Sunday magazine, with the provocative title, “Can Big Data Tell Us What Clinical Trials Don’t?,” showed how medical practitioners can tap big data to aid treatment decisions. It recounted the case of a 13-year-old girl with symptoms of kidney failure who’d been airlifted to Packard Children’s Hospital at Stanford University, and quickly diagnosed with lupus, along with several complications.

The on-call rheumatologist, recalling similar cases, wanted to give the girl anti-coagulant medication, fearing a potentially fatal blood clot, but other doctors disagreed. Finding no relevant medical literature, the medical team resolved the deadlock by running a statistical analysis of pediatric patients with lupus who had been admitted to the hospital during the past five years.

Their statistical search found blood clots had developed in 10 of 98 patients with similar symptoms who did not get anti-coagulants. Satisfied, the medical team administered the anti-clotting medication to the girl, who did not develop thrombosis or side-effects from the medication.

Obstacles remain to such real-time use of data-mining medical databases for research purposes, notably privacy protections under the Health Insurance Portability and Accountability Act (or HIPPA). A quick illustration: After the Stanford rheumatologist wrote up the data-mining analysis for the New England Journal of Medicine, hospital officials cautioned against further efforts of the type until they devised a patient privacy framework.

Many see additional data sources capable of modifying clinical trials or practice. At the 2013 Forbes Healthcare Summit, Glen de Vries, president of clinical trial database provider Medidata, advocated use of such devices like wearable monitors, sensors and even smartphone apps to track trial participants’ activities and reactions. Rather than measuring how far a cardiac drug tester can walk by bringing him to a doctor’s office for a treadmill test, de Vries suggested furnishing enrollees with devices like FitBits or Nike Fuel bands.

To Battle Ebola, Drug Makers Press for Cure, Vaccine

November 18th, 2014

clinical trials

With the Ebola virus ravaging West Africa and causing growing anxiety over the potential for outbreaks in Europe, America and elsewhere, drug developers are pressing to discover an effective treatment and develop a vaccine against the lethal hemorrhagic fever.

No drug is yet approved as safe and effective for treating or preventing Ebola. Current treatment for those stricken by the disease is to balance fluids and electrolytes, maintain blood pressure and oxygen, and treat complications. In Guinea, Liberia and Sierra Leone, where the disease has attained epidemic proportions, the death rate is about 70% of those infected.

As an emergency measure, ZMapp, developed by San Diego-based Mapp Biopharmaceutical, is being administered in some cases. For example, ZMapp was also given to two U.S. medical missionaries who recovered after contracting the disease in Liberia, where the disease has already claimed thousands of lives.

The experimental therapy is a cocktail drug combining three monoclonal antibodies. The company’s current molecular biology process uses tobacco plants to produce each antibody separately, and then must get a certificate of analysis for each before combining them into the combination drug ZMapp.

The company is working to boost yields from its plant-based production method, and ecently joined with another producer to see if yields be would boosted by using an animal-based biotech production method, which employs genetically-modified CHO cells from Chinese hamster ovaries cultivated in sterile tanks. The plant production method, carried out by the Reynolds tobacco company’s Kentucky BioProcessing subsidiary, is faster and cheaper, but not as suitable for large-scale production as more conventional biotechnology methods.

ZMapp is being tested in animal experiments done by the US Army Medical Research Institute of Infectious Disease, with assistance from the Bill and Melinda Gates Foundation. The animal tests are designed to see if the drug has the same effects at lower doses, since supplies of ZMapp are very limited.

On September 2, Mapp Biopharmaceutical received a $24.9 million contract from the U.S. Department of Health and Human Services to assist the company’s manufacturing and non-clinical activities. Part of the 18-month contract will also bring HHS technical support for the drug company’s effort to manufacture enough of the drug to support human safety clinical studies. The company had planned to start clinical studies in 2015, and is now working to accelerate its efforts to win FDA approval.

In addition, two Ebola-preventing vaccines have started clinical trials in humans. Even if early results from those tests are positive, no vaccine is expected to receive FDA approval and reach the marker until next year at the earliest.

At the National Institutes of Health (NIH), Phase 1 safety and effectiveness clinical trials in healthy adults have begun for an investigational vaccine jointly developed by the National Institute of Allergy and Infectious Diseases (NIAID) and GlaxoSmithKline, and for an experimental Ebola vaccine from the Public Health Agency of Canada. The NIAID-GSK vaccine will also receive clinical trials in the UK and several African nations. Further anti-Ebola products are likely to follow in starting clinical trials, perhaps as early as next year.

Questions to Ask about a Clinical Trial You’re Considering

November 1st, 2014

While trying to decide whether to sign onto a clinical trial, you’re likely to have lots of uncertainties and gaps in your knowledge. You may even be unsure on how to go about reaching this important decision.

The enrollment process — especially the requirement that you get detailed information from the researchers and have a chance to get your questions answered – should eventually equip you to your choice. (Note: the U.S. Food and Drug Administration, which wrote the rules on the informed consent requirement and oversees compliance with the mandate, earlier this year proposed revised guidance on the process and is taking public comment until October 27).

You should inform yourself as fully as possible about the clinical trial before deciding on whether to take part. But to give you a head start, here’s a fairly comprehensive summary of the issues you may want to consider.

Questions on Study Design and Administration

What’s the purpose of the study?

It could be to explore whether a therapy would be safe and effective, to probe whether it has significant side effects, to establish dosage levels, to gauge the comparative effects of two or more competing treatments.

How many people will participate in the study? How will they be selected? How long is the study supposed to last, and what will participants be asked to do?

Clinical test sizes vary, usually with small groups studied in the early stages, moving to larger groups as it moves nearer to approval (and, sometimes, clinical trials study treatments already on the market). While some trials seek healthy volunteers, participants are often selected from patients with a condition being studied, or a predisposition toward it.

Why does the research believe the treatment being studied might be an improvement? Has the treatment been tested previously? If so, what were the results? What process is being used to monitor participant safety and study results? Has the proposed study been reviewed and approved?

Since there can be numerous levels in the process – an Institutional Review Board and possibly an independent science review board, and perhaps additional levels, such as an independent safety review panel or Data and Safety Monitoring Board, you might also ask about any approvals that are still awaited.

Questions on Treatments and Possible Risks and Benefits

What are the study’s possible short-term and long-term benefits for participants? The possible short-term and long-term risks? How do these compare with those for any other available treatments?

During a trial, participants will receive medical treatment and screening; randomized tests give some participants a treatment being tested, but give a non-active placebo to other participants. Some treatments may bring improved health in some participants, but others may experience adverse reactions or side effects.

What tests, treatments and procedures will the trial include? Can I take my regular medicines during the trial? Where will I be treated, on what schedule, and who will be in charge?

Other Questions

How is the trial funded, and will I have to pay any costs? Will any of the treatments or tests be painful or affect my everyday life? Will I have other expenses (e.g. travel or childcare) from being in the trial?

If I have problems or need more information, who should I contact?

How the Rights and Interests of Clinical Trial Participants Are Protected

October 15th, 2014

clinical trial participantsAnyone considering whether to take part in a clinical trial probably realizes the opportunity not only offers a chance to receive state-of the-art healthcare and preview a new therapy, but also to contribute to science and society. Despite these benefits, it’s only natural to want to weigh the pros and cons, to consider what potential risks trial participants may face.

So how much does someone considering whether to join a clinical trial know about the risks and rewards of the trial, and how are they protected as they make their decision — and beyond that, if they choose to take part in the trial?
The first way would-be clinical trial participants are protected is through the informed consent process. Under regulations written and overseen by the Food and Drug Administration, every clinical trial participant must have given his or her informed consent, given after receiving detailed information on the trial.

Informed consent disclosures come from the doctors and nurses on the research team; they explain in detail the purpose, procedures, treatments and potential risks and benefits of the trial under consideration. They must also make clear the rights of participants in the trial, including their right to decide and, if they opt to participate, to later change their mind and withdraw from the trial at any time.
The prospective trial participant must have an opportunity to discuss the trial with the principal investigator and others on the research team. The information provided about the trial must come in language the prospective participant can understand. Finally, if willing to join the trial, the participant signs an informed consent form with the detailed information on the trial.

Beyond the informed consent process, under federal rules, every health institution conducting clinical trials must have an Institutional Review Board, or IRB. This body, composed of at least five members, has the duty to review clinical trial design and management to ensure that participants’ rights are being protected. Every trial must be reviewed at least annually, and the IRB has the power to change or even halt a clinical trial that has departed from its approved protocol or appears to be harming participants.

IRB members must include at least one scientist and at least one non-scientist. At least one member must not be affiliated with the healthcare institution and not closely related to anyone with ties to the institution. Many IRB members are physicians, other healthcare professionals, patient advocates, social workers or community leaders.
Further, before a government-funded clinical trial can start signing up participants, a scientific review panel must review and approve its clinical protocol; many privately-funded trials have opted for a similar preliminary review by scientific experts.

As further safeguards, some clinical trials also use safety monitoring committees or a Data and Safety Monitoring Board (DMSB), an independent panel of medical experts, statisticians and others that review early trial results and advise the IRB. Phase III clinical trials must have a DSMB, which can end a clinical trial over safety issues, or if it determines trial results have been achieved.

Treatment for Peripheral Arterial Disease or PAD

August 25th, 2014

Did You Know? Severe intermittent pain in your legs that is relieved by a short rest is known as Intermittent Claudication and is the early stage of Peripheral Arterial Disease or PAD.

PAD occurs when extra cholesterol and other fats circulating in the blood collect in the walls of the arteries that supply blood to your limbs. This buildup—called plaque—narrows your arteries, often reducing or blocking the flow of blood. People with PAD can experience leg pain with walking, typically an aching in the calves, thighs and/or buttocks (intermittent claudication). When the disease becomes more severe, people may have pain in the leg at rest, or even foot ulceration and gangrene.

Cutting Edge Therapies Are Being Tested
A clinical trial is currently underway that is testing the use of cell therapy using placenta derived cells (these are not embryonic stem cells) which may increase the blood flow in the arteries of the lower legs by generating new blood vessels. If proven effective, this medical approach could potentially enhance one’s quality of life by reducing leg pain.

To learn more about this clinical trial and to see if you qualify to participate call our information line toll free at 877-997-8839 or click here to visit www.clinicaltrialspotlight.com

Getting More Elderly Patients into Clinical Trials

June 13th, 2014

Elderly persons comprise a large, and the fastest-growing, portion of the population in the U.S. and other advanced nations. They are also make up the lion’s share of patients for certain health conditions, including cancer, cardiovascular disease, arthritis, and Parkinson’s disease, among others. The elderly also are the main users for many medications, especially those treating chronic conditions.

So it’s more than a little ironic that elderly patients are greatly underrepresented in clinical trials for remedies for those conditions. For example, three-quarters of U.S. patients who are diagnosed with lung cancer are at least 65 years old, but only a little more than a third of the patients in clinical trials for lung cancer were in that age group.

Similarly, in a widely-noted study from 2011, University of Michigan researchers analyzed 109 reports issued in 2007 on clinical trial projects. They found that fully one-fifth of those studies imposed age limits, most commonly 65, on trial participants despite no apparent medical justification (the practice was even more pronounced ten years earlier, when over one-third of trials did that).

Of the rest of the clinical trials in 2007, about half set non-age criteria for participants, such as rejecting those who were frail or mentally impaired, that were in practice far more likely to screen out older persons.

Many reasons have been advanced to explain under-representation of the elderly in clinical trials. Some point to medical factors, such as higher risks of adverse effects, lower life expectancy, and the greater likelihood older patients will have multiple ailments and take other medications.

Psychological and ethical challenges may also pose obstacles in obtaining informed consent, and elderly patients may also have greater difficulty in traveling to get treatment, or in getting support needed to follow treatment protocols.

Despite that, a consensus is building among researchers against many age restrictions in clinical trials. Twenty years ago, the International Conference on Harmonisation (ICH), an international initiative of U.S., European and Japanese health experts interested in setting good practice standards for clinical trials, noted it was impossible to predict from clinical trials that exclude elderly patients “all potential differences in pharmacokinetics, pharmacodynamics, disease-drug interactions, drug-drug interactions, and clinical response” that geriatric patients might experience.

The ICH called for including elderly in clinical trials for all therapies intended for adults. Its “Studies in Support of Special Populations: Geriatrics,” issued in 1994, urged clinical trial protocols to avoid arbitrary upper age limits.

It also recommended not excluding elderly from trials even if they have other ailments, since doing so prevents uncovering interactions of multiple drugs or diseases. In fact, the European Medicines Agency has refused to approve at least one drug for use for patients over age 80 because clinical trials for the drug had included very few patients in that age group.

In the U.S., Food and Drug Administration guidance advises researchers not to exclude trial participants solely on the basis of age, and also urges inclusion of “an appropriate representation” of elderly patients in clinical trials to gauge safety and effectiveness in older patients, and to allow comparisons with their impact on non-elderly patients.

Increasingly, medical researchers are recommending that clinical trial sponsors raise age limits for trial participants (say, from 65 to 75) or eliminate them entirely, and that any age limits in trial protocols be medically justified.

They also urge building into trial designs one or more subgroups of elderly patients, based on their other ailments and medications, to better study interactions. They also want contract research organizations to train investigators better in dealing with elderly patients’ special difficulties and to pay more attention to accommodating them.

These Statics Regarding Amputation Rates in the United States are Staggering

May 5th, 2014
  • Among the 2 million people in the United States living with limb loss, the main causes are vascular disease (54%) – including diabetes and peripheral arterial disease- trauma (45%) and cancer (less than 2%)
  • Approximately 185,000 amputations occur in the United States each year!
  • In 2009, hospital costs associated with amputations totaled more than $8.3 billion!
  • Nearly half of the individuals who have an amputation due to vascular disease will die within 5 years. This is higher than the five year mortality rates for breast cancer, colon cancer, and prostate cancer!
  • African-Americans are up to four times more likely to have an amputation than White Americans!
  • Of person with diabetes who have a lower extremity amputation, up to 55% will require amputation of the second leg within 2-3 years!

How a Cancer Patient Should Decide Whether to Join a Clinical Trial

April 30th, 2014

clinical trialsCancer is the second-leading cause of death in America, trailing only heart disease, but progress is being made. According to the National Institutes of Health’s National Cancer Institute (NCI), cancer incidence has declined since 1998, and there have been continuing declines in both the death rates for the four most prevalent forms of cancers (prostate, breast, lung and colorectal) and in the combined overall death rate from all types of cancer.

Much of this progress can be credited to major advances researchers have made in molecular biology and genomics, which have helped revolutionize cancer screening tools and therapies. Cancer patients have also contributed to these discoveries by participating in clinical research trials. In some cases, when a cancer patient does not respond to established treatments, a clinical trial may offer an opportunity to access new therapies under development.

Deciding whether to seek out and join a clinical trial is a serious decision for cancer patients; as a first step they should consult with their doctor, in light of the patient’s complete diagnosis and the likely effectiveness of standard treatments.

Patients have several resources for finding access to clinical trials. They can speak with their physician or they can search the national government database website www.clinicaltrials.gov. This is a comprehensive website that lists all clinical trials and can be very overwhelming and difficult to understand. For more user friendly and easier to understand websites, we recommend www.clinicaltrialspotlight.com or www.ciscrp.org to name a few.

Clinical research trials vary substantially in their eligibility criteria, which may involve such factors as the type and stage of a cancer being studied, patient age, treatment and medication history, or lab test results. Clinical test protocols also sometimes look for participants with specific demographic or genetic factors.

Any clinical trial may have possible benefits or drawbacks, so an informed understanding and careful weighing of both is essential. The patient needs to take into account both the potential benefits (access to newly developing therapies, helping researchers and other patients,), and the possible risks (known and possibly unknown side effects, perhaps not knowing whether the test is providing the remedy being tested or a control group substitute, ).

Each clinical trial will have written materials summarizing the investigation plan, and staff to answer questions. After obtaining information on clinical tests in which you think you may be interested, talk things over with your family, doctor and other advisers.

Remember a clinical trial needs your written informed consent to include you, and you will be free to drop out at any time. Often times, you will be compensated for your time and travel costs and all study related expenses are at no cost to you. (the informed consent will will detail this). Most trials do not require that you have health insurance , and the Affordable Care Act bars insurers from dropping your coverage because you took part in a clinical trial.

If you find a suitable clinical trial and choose to take part, you may find comfort in knowing that, with the knowledge gained through increasingly sophisticated and focused clinical trials, researchers aim to achieve, in the words of NCI, “a future where all cancers are uncommon and easily treated.”

Rare-Disease Researchers Could Teach Drug Makers Important Lessons

March 28th, 2014

In a recent column in Medical Marketing & Media, the founder and president of a digital relationship marketing firm with a long history in assisting those searching for remedies for rare diseases offers advice on how pharmaceutical companies could profit from the experience of those working on so-called “orphan” drugs.

Siren Interactive president and founder Wendy White notes fully a third of the novel drugs approved by the Food and Drug Administration last year are orphan drugs, treating rare diseases which each affect no more than 200,000 people in the U.S. The almost 7,000 rare diseases, however, collectively affect about 10% of the U.S. population. Since 80% of the conditions are genetic in origin, they are very likely to affect children. Only about 5% have an FDA-approved therapy.
A frequent author and speaker on rare-drug issues, White begins by noting that fully a third of the new drugs approved by the Food and Drug Administration last year were for rare remedies, and more are in the pipeline for expedited review.

In fact, two of the nine novel orphan drugs cleared by the FDA in 2013 practically set speed records: Genentech’s chronic lymphocytic leukemia drug Gazyva won approval in just a little over six months, and Janssen’s mantle cell lymphoma drug Imbruvica cleared the agency in just four-and-a-half months.

That record of success is partly due, White notes, to government incentives for rare-drug remedies, and to their profitability (in a market estimated to hit $127 billion by 2018, their return on investment is 1.7% higher than for conventional drugs, White notes, citing a 2013 report.) But, she adds, credit should also go to lessons those drug makers have learned that the overall pharmaceutical industry would do well to heed.

White points to five lessons learned that have benefitted orphan drug makers. First, she notes, large drug firms sometimes make the mistake of viewing their operations as compartmentalized, seeing clinical trials as separate from their manufacturing, marketing and other operations.

But rare drug firms, on the other hand, have discovered that, in White’s words, “brand building begins long before there is a brand.” So it’s crucially important for pharma firms to engage with affected communities early on, while planning and running clinical trials. What they do there in areas such as sharing data, providing drugs for compassionate use, and speedily reimbursing trial participants will do much to impair or enhance their reputation.

Orphan drug makers have also learned the importance of using social media in reaching close-knit rare drug communities. By failing to reach out through these widely shared media to tell their story, uncommunicative drug firms virtually guarantee someone else will tell it for them.

To gain maximum support, rare drug makers have also become expert in providing personalized support to those affected by the diseases they research. Leveraging their information and resources, they get involved in creating collaborative ways to educate the community and the public, and to help deliver services. By extending their view beyond the laboratory, such efforts pay dividends by building trust and cooperation, especially in times of trouble (as an example, she cites Genzyme’s active involvement with patient communities as helping the company weather some past supply problems).

Finally, White adds, rare drug companies recognize that patients look for innovations that improve their care and quality of life, and working together with patients, support groups and other stakeholders is the most effective way to achieve those outcomes.