Of all the eye research developments reported on the VisionAware blog, it is stem cell research for eye disease that generates the most inquiries from our readers. Many readers request information about stem cells, assuming that this is an established and widely-performed treatment for eye disease; others ask for help in finding a doctor who will administer “stem cell treatments.”
In response to these inquiries, my message is always the same: “Although stem cell research for eye disease has produced a small number of interesting results, it is in its very earliest safety-testing stages and must be subjected to additional, longer-term, rigorous study and clinical trials, encompassing many more years of closely monitored research. Success in this area is not a foregone conclusion. At present, stem cell research is fraught with numerous stops and starts, high expectations, and frequent disappointments.”
It’s important to know that even if a clinical trial for eye disease is listed in ClinicalTrials.gov, it does not always mean that the trial has been approved by the United States Food and Drug Administration (FDA) or the National Institutes of Health (NIH). Patients should always consult with their own physicians before seeking to participate in any clinical trial.
Furthermore, if the sponsors of the treatment or trial request payment from the patient to participate, this raises a significant “red flag.” Such a situation is called “pay to participate” and raises a number of profound ethical issues, including the lack of equal opportunity for all to participate, and the unfavorable risk/benefit ratio of participating in the research.
A recent article on the VisionAware blog, titled Our Readers Want to Know: What Is the Progress of Stem Cell Research for Eye Disease? Answer: It Has a Very Long Way to Go, also addressed a number of safety issues surrounding experimental stem cell trials for age-related macular degeneration (AMD), particularly the risks of tumor formation and potential immune rejection.
In March, the New York Times published a detailed report of three women with AMD who suffered severe, permanent eye damage after stem cells were injected into their eyes in an unproven treatment at U.S. Stem Cell, a private clinic at Sawgrass Medical Center in Sunrise, Florida.
Most recently, University of Minnesota bioethicist Leigh Turner, in the July issue of Regenerative Medicine, has scrutinized the ClinicalTrials.gov website and concluded that “Individuals considering enrolling in [studies listed on ClinicalTrials.gov], advocates for patients, and research subjects, health researchers, and officials at both the NIH and the FDA need to be aware that some businesses are using the ClinicalTrials.gov registry to promote stem cell interventions that study subjects are being charged to receive.”
In other words, consumers and their physicians should be aware that some of these businesses have learned to repurpose ClinicalTrials.gov as a marketing and public relations tool to promote their unproven stem cell products and interventions.
About the Research
This latest clinical trial and macular degeneration research, titled ClinicalTrials.gov, stem cells and ‘pay-to-participate’ clinical studies, has been published online ahead of print as an open-source article (with registration required) in the July 2017 issue of Regenerative Medicine, which “provides a forum to address the important challenges and advances in stem cell research and regenerative medicine.” The author is Leigh Turner, Ph.D., from the Center for Bioethics, School of Public Health and College of Pharmacy, University of Minnesota.
What Are Clinical Trials?
ClinicalTrials.gov is a registry and searchable database of ongoing, concluded, and suspended clinical trials. The National Institutes of Health (NIH) opened ClinicalTrials.gov to the public in 2000, with a mission of giving critically ill people more information about monitored experimental treatments that could save their lives.
The database is also intended, according to Leigh, “to increase transparency in clinical research; facilitate registration of clinical trials in a public database; help prospective study participants identify trials for which they might be eligible; and enroll and make results of studies publicly available.”
In order to receive approval from the FDA, a new drug or treatment must be proven to be both safe and effective by undergoing a rigorous series of controlled unbiased studies. To prevent bias, neither the patient nor the examiners can know which patients receive the actual treatment and which are the untreated (or “control”) subjects.
These are called “double blind” or “double masked” studies and usually yield the most reliable results. The medication is coded and patients are placed at random into either the treatment or control group. When the study is concluded, the code is revealed and it is then possible to determine who received the actual drug and who received the inactive substance, or placebo.
As defined by the U.S. National Institutes of Health (NIH), most clinical trials are designated as Phase 1, 2, or 3, based on the questions the study is seeking to answer:
- In Phase 1 clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe and effective dosage range, and identify possible side effects.
- In Phase 2 clinical trials, the study drug or treatment is given to a larger group of people (100-300) to determine if it is effective and to further evaluate its safety.
- In Phase 3 studies, the study drug or treatment is given to even larger groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
- In Phase 4 studies, after the FDA has approved the drug, continuing studies will determine additional information, such as the drug’s risks, side effects, benefits, and optimal use.
More About the Regenerative Medicine Research
Excerpted from ClinicalTrials.gov, stem cells and ‘pay-to-participate’ clinical studies, with the full article available online:
Numerous US businesses that engage in direct-to-consumer advertising of purported stem cell treatments recruit clients by registering clinical studies on ClinicalTrials.gov. Some studies registered by businesses selling putative “stem cell therapies” disclose that study subjects are charged. The studies are explicitly described as being “patient-funded,” “patient sponsored” or “self-funded.”
However, other studies registered on ClinicalTrials.gov by businesses selling stem cell interventions do not reveal that study subjects are charged to participate in clinical research. It is only when interested individuals contact sponsors, investigators or clinic employees and inquire about enrolling in the studies that they are then informed they must pay to participate.
Listing studies on ClinicalTrials.gov is an effective way for businesses selling stem cell interventions to solicit prospective clients. One such company was recently the subject of considerable news media scrutiny after clinicians independent from the business published a study documenting that three of its patients suffered severe vision loss after paying $5,000 per person for stem cell interventions that were supposed to treat their age-related macular degeneration. At least one of the women who were blinded reportedly contacted the stem cell clinic after learning about the one of the clinical studies this business had registered on ClinicalTrials.gov.
There are no reliable estimates of how many individuals pay for stem cell interventions advertised by businesses that use ClinicalTrials.gov listings and other marketing tools to solicit individuals searching for treatments. Nonetheless, such listings play an important role in promoting particular companies and clinics. The studies they register on ClinicalTrials.gov help confer legitimacy on their promotional claims and commercial activities.
Information about whether clinical studies have been approved by institutional review boards (IRBs) must be submitted during the process of registering trials in ClinicalTrials.gov. However, before being registered on ClinicalTrials.gov, clinical studies are not screened and scrutinized to determine whether they are subject to review and clearance or approval by the FDA or other national regulatory bodies in addition to IRB review. Registration works on an “honor system” basis.
According to a disclaimer on the ClinicalTrials.gov website, “Information on ClinicalTrials.gov is provided by study sponsors and investigators, and they are responsible for ensuring that the studies follow all applicable laws and regulations.” This failure to scrutinize whether submitted studies comply with applicable regulations has created a situation in which sponsors and investigators can register clinical studies and deposit them in the database without careful screening by NIH employees responsible for maintaining the database.
You can read the article in its entirety at ClinicalTrials.gov, stem cells and ‘pay-to-participate’ clinical studies, via Regenerative Medicine.
A Harmful Stem Cell Treatment in Florida
Excerpted from Patients Lose Sight After Stem Cells Are Injected Into Their Eyes, via the New York Times:
Three women suffered severe, permanent eye damage after stem cells were injected into their eyes, in an unproven treatment at a loosely regulated clinic in Florida, doctors reported in an article published in March in the New England Journal of Medicine.
One, 72, went completely blind from the injections, and the others, 78 and 88, lost much of their eyesight. Before the procedure, all had some visual impairment but could see well enough to drive. The cases expose gaps in the ability of government health agencies to protect consumers from unproven treatments offered by entrepreneurs who promote the supposed healing power of stem cells.
The women had macular degeneration, an eye disease that causes vision loss, and they paid $5,000 each to receive stem-cell injections in 2015 at a private clinic in Sunrise, Florida. The clinic was part of a company then called Bioheart, now called U.S. Stem Cell. Staff members there used liposuction to suck fat out of the women’s bellies, and then extracted stem cells from the fat to inject into the women’s eyes.
Two of the eye patients sued the clinic and settled, but it has faced no other penalties. [The clinic stated that] it no longer treats eyes, but continues to treat five to 20 patients a week for other problems like torn knee cartilage and degenerating spinal discs.
All three women found U.S. Stem Cell because it had listed a study on a government website, clinicaltrials.gov — provided by the National Institutes of Health. Two later told doctors they thought they were participating in government-approved research. But no study ever took place, and the proposed study on the site had no government endorsement. Clinical trials do not need government approval to be listed on the website. Legitimate research rarely, if ever, charges patients to participate, scientists say, so the fees should have been a red flag. But many people do not know that.
The women in Florida suffered detached retinas, in which the thin layer of light-sensing cells that send signals to the optic nerve pulls away from the back of the eye — a condition that usually needs prompt surgery to prevent blindness. Doctors who examined the patients said they suspected that the stem cells had grown onto the retina and then contracted, pulling it off the eyeball.
A Summary of the Regenerative Medicine Findings and Recommendations
From the Executive Summary of ClinicalTrials.gov, stem cells and ‘pay-to-participate’ clinical studies, with the full article available online:
- Patients and their advocates, health researchers, and many other parties use ClinicalTrials.gov for a variety of purposes. Many individuals trying to find clinical studies for which they are eligible to participate regard ClinicalTrials.gov as a trustworthy, reliable source of information.
- Carefully designed and properly conducted clinical studies are valuable tools for generating meaningful safety and efficacy data while minimizing risks to research subjects and promoting informed decision-making by prospective research participants.
- However, clinical studies, including studies that are poorly designed and suffer from numerous scientific, ethical and regulatory shortcomings, can also be used as marketing devices to recruit clients.
- Numerous US businesses that engage in direct-to-consumer advertising of purported stem cell treatments also charge individuals to participate in clinical studies in which stem cells are administered. Some of these companies use clinical studies listed in ClinicalTrials.gov to sell stem cell interventions provided in the context of “patient-funded.” “patient-sponsored,” or “self-funded” studies.
- Inclusion in ClinicalTrials.gov of “pay-to-participate” studies that have not been subject to US FDA oversight and careful screening by NIH officials risks compromising the integrity and utility of the database.
- Listing “pay-to-participate” studies in the database also risks confusing prospective study participants by blurring important distinctions between commercialized medical treatments and clinical research evaluating interventions for which conclusive evidence of safety and efficacy is lacking.
- There is an urgent need for careful screening of clinical studies before they are registered with ClinicalTrials.gov.
The takeaway: Patients should always consult with their own physicians before seeking to participate in any clinical trial. Be an informed, careful, and wise consumer.
- The Reality and Costs of Gene Therapy for Eye Disease: Who Will (or Can) Pay?
- Treating Macular Degeneration with Gene Therapy: New Research Shows Promise but Also Has Limitations