WHAT’S NEW – Champions of The Paperless Clinical Trial and First FDA Approval Using eSource When Entering Data in Real-Time at the Clinic Visit

Champions of The Paperless Clinical Trial and First FDA Approval Using eSource When Entering Data in Real-Time at the Clinic Visit

 

Target Health Inc. is a software company that provides CRO services, and a CRO that includes software services as part of its offering. Some of our clients just use our software, while others want us to provide CRO services, fully integrated with our software suite. In our most recent paperless clinical program in dermatology, sponsored by Big Pharma, 65% of patients electronically signed the informed consent document, and 90% of forms were entered on the day of the clinic visit; over the course of 12 months, there were just 29 monitoring visits at 13 sites, including 3 sites in Japan, while 151 central monitoring reports were issued and electronically signed. All features, including the monitoring reports, were at one website with no dedicated devices. A major program is ongoing in autism and other programs are starting in psychiatry and diabetes.

 

The first-ever FDA clearance of a direct data entry, eSource program, occurred in 2015.  There were FDA inspections at 3 medical centers and at Target Health; and only one 483 at one of the sites, which was easily addressed. The results were recently published in JAMA.

 

Below describes our software suite:

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.

 

Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor

 

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Gene Therapy Halts Progression of Cerebral Adrenoleukodystrophy in Clinical Trial

Adrenoleukodystrophy, and MRI showing T2 weighted axial scan at the level of the caudate heads demonstrates marked loss of posterior white matter, with reduced volume and increased signal intensity. The anterior white matter is spared. Features are consistent with X-linked adrenoleukodystrophy. Sources: Radiopediacase From Wikimedia Commons, the free media repository

 

 

Adrenoleukodystrophy (ALD) is a disease linked to the X chromosome and was featured in the 1992 movie “Lorenzo’s Oil.“ This devastating neurodegenerative disease typically affects young boys and causes death within 10 years. It is a result of fatty acid buildup caused by the relevant enzymes not functioning properly, which then causes damage to the myelin sheathes of the 1) ___, resulting in seizures and hyperactivity. Other side effects include problems with speaking, listening, and understanding verbal instructions. ALD is a disorder of peroxisomal fatty acid beta oxidation which results in the accumulation of very long chain fatty acids in tissues throughout the 2) ___. The most severely affected tissues are the myelin in the central nervous system, the adrenal cortex, and the Leydig cells in the testes.

 

Clinically, ALD is a heterogeneous disorder, presenting with several distinct phenotypes, and no clear pattern of genotype-phenotype correlation. As an X-linked disorder, ALD presents most commonly in males, however approximately 50% of heterozygote 3) ___ show some symptoms later in life. Approximately two-thirds of ALD patients will present with the childhood cerebral form of the disease, which is the most severe form. It is characterized by normal development in early 4) ___, followed by rapid degeneration to a vegetative state. The other forms of ALD vary in terms of onset and clinical severity, ranging from adrenal insufficiency to progressive paraparesis in early adulthood (this form of the disease is typically known as adrenomyeloneuropathy).

 

ALD is caused by mutations in ABCD1, a gene located on the X chromosome that codes for ALD, a peroxisomal membrane transporter protein. The exact mechanism of the pathogenesis of the various forms of ALD is not known. Biochemically, individuals with ALD show very high levels of unbranched, saturated, very long chain fatty acids, particularly cerotic acid. The level of cerotic 5) ___ in plasma does not correlate with clinical presentation. Treatment options for ALD are limited. Dietary treatment is with Lorenzo’s oil. For the childhood cerebral form, stem 6) ___ transplant and gene therapy are options if the disease is detected early in the clinical course. Adrenal insufficiency in ALD patients can be successfully treated. ALD is the most common peroxisomal inborn error of metabolism, with an incidence estimated between 1:18,000 and 1:50,000. It does not have a significantly higher incidence in any specific ethnic groups.

 

In a recent clinical trial, a gene therapy to treat cerebral adrenoleukodystrophy (CALD) effectively stabilized the disease’s progression in 88% of patients. According to the results, published in the New England Journal of Medicine, 15 of 17 patients had stable neurologic functioning more than two years on average after receiving the gene 7) ___, which was administered in a clinical trial sponsored by bluebird bio. It is one of the largest gene therapy trials targeting a single-gene disease to be published to date. “Although we need to continue to follow the patients to determine the long-term outcome of the gene therapy, so far it has effectively arrested the progress of CALD in these young boys,“ says David A. Williams, MD, chief scientific officer and senior vice-president for research at Boston Children’s Hospital and president of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and the lead author of the study. “This is a devastating disease, and we are all quite grateful that the patients and their families chose to participate in the trial.“ The treatment leverages bluebird bio’s proprietary Lenti-D gene therapy to deliver the functional gene to patients’ stem cells in the laboratory.

 

According to Williams, “This treatment results from more than two decades of investment in basic 8) ___ therapy research by the NIH and others.“ “Since it was first described 100 years ago, ALD has robbed the function of children who, up until the disease’s onset, had been developing normally,“ says Florian Eichler, MD, co-lead author on the study.“ Eichel added that “These are children who have been growing and thriving, and then suddenly, their parents witness this devastating decline that starts with personality changes and then progresses to motor problems and loss of their ability to walk and talk.“

 

Until now, stem cell transplantation using cells donated by another person has been the only known effective therapy for CALD. Yet, its efficacy is drastically reduced if performed during later stages of neurodegeneration and usually works best with a disease-free matched sibling donor, which fewer than one-quarter of CALD patients have. To perform the gene therapy, clinicians first collect a patient’s blood stem cells, which give rise to all mature 9) ___ cells. In a highly-specialized laboratory that contains a clean room for preparation of medicines, a viral vector is used to insert a correct version of the faulty gene into the patient’s stem cells. Then, after the patient receives chemotherapy to make room for the genetically altered blood stem cells in the bone marrow, the cells are infused back into the patient’s bloodstream. According to Eichler, “In my clinic, the impact of this trial has been phenomenal.“ “Boys without a donor match for stem-cell transplant were often passing away within a year or two of their diagnosis. Now, with early diagnosis and gene therapy, these boys are living longer and some are thriving enough to play sports and participate in other normal day-to-day activities.“

 

At the latest follow-up, all patients who participated in the clinical trial were expressing functional ALD protein, which their bodies had been unable to produce prior to gene therapy. The trial is ongoing and has received regulatory approval to expand patient numbers. “There are two great advantages to gene therapy“ according to Williams. “The first is that patients don’t have to wait to find a donor match. The second is that, because we use their own, gene-modified stem cells, there’s no risk of graft-versus-host-disease and the patients do not require any 10) ___ drugs, which can have very significant, even fatal, side effects.“

 

The ALD gene therapy trial is part of a robust and growing portfolio of pediatric gene therapy trials at Dana-Farber/Boston Children’s that also includes clinical trials for X-linked severe combined immune deficiency (“bubble boy“ disease), chronic granulomas disease, a recently completed trial in Wiskott-Aldrich Syndrome and the use of gene therapy to treat some types of childhood leukemia using “CAR T cells.“ In addition, the Food and Drug Administration has just approved a ground-breaking study at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center for the use of gene therapy to cure sickle cell disease. Sources: Boston Children’s Hospital; New England Journal of Medicine, 2017; DOI: 10.1056/NEJMoa1700554; “Gene therapy halts progression of cerebral adrenoleukodystrophy in clinical trial: The devastating neurodegenerative disease typically affects young boys and causes death within 10 years.“ ScienceDaily, 4 October 2017; Wikipedia; nih.gov.

 

ANSWERS: 1) nerves; 2) body; 3) females; 4) childhood; 5) acid; 6) cell; 7) therapy; 8) gene; 9) blood; 10) immunosuppression

 

History of Adrenoleukodystrophy

A movie, made in 1993 called “Lorenzo’s Oil“ tells the story of a young boy, Lorenzo Odone, who had Adrenoleukodystrophy. His parents were the creators of an oil, still used today, in the diets of people with this terrible disease. Today, this dietary aid is called Lorenzo’s Oil, named after the same substance used to relieve Lorenzo Odone. He recently died in 2008, at the age of 29, after being diagnosed with ALD at age 5 in 1984. http://wiki.ggc.usg.edu/wiki/Adrenoleukodystrophy

 

Timeline of the History of ALD – ALD Database

August 23rd, 2017 |

Marc Engelen, M.D., Ph.D. and Stephan Kemp, Ph.D.

 

1910: In retrospect, Haberfeld and Spieler presented the first clinical description of a patient with X-linked adrenoleukodystrophy (Haberfeld and Spieler, 1910). A previously healthy 6 year old boy developed a deeply bronzed skin (hyperpigmentation), impaired visual acuity, and his school performance deteriorated. The following months, this boy became incontinent, lost his ability to speak and developed spastic tetraparesis, which eventually progressed to an inability to walk. He was hospitalized at the age of 7, and died 8 months later. An older brother had died of a similar illness at the age of 8. Postmortem histological examination of the brain revealed extensive changes in brain white matter, combined with perivascular accumulation of lymphocytes and plasma cells in the nervous system, indicating an inflammatory response.

1922: Siemerling and Creutzfeldt reported the case of a boy with a similar disease progression, including the dark skin and neuropathological findings as in the case described by Haberfeld & Spieler in 1910, except that atrophy of the adrenal cortex was documented.

1963: By now nine comparable cases had been reported. The fact that all patients were males suggested X-linked recessive inheritance (Fanconi et al. 1963).

1970: The name adrenoleukodystrophy was introduced based on the striking association of a leukodystrophy with primary adrenocortical (adrenal) insufficiency (Blaw, 1970).

1972: The key to all subsequent knowledge about the disease was the observation made by Powers, Schaumburg, and Johnson that adrenal cells of ALD patients contained characteristic lipid inclusions (fat droplets), followed by the demonstration that these fat droplets consisted of cholesterol esters that contained a striking and characteristic excess of very long-chain fatty acids (VLCFA).

1976: A more slowly progressive adult form of the disease characterized by adrenal insufficiency, myelopathy and peripheral neuropathy was described (Budka et al. 1976). A year later, five more cases were reported by Griffin et al. who proposed this clinical presentation of ALD to be named adrenomyeloneuropathy (AMN) (Griffin et al. 1977Schaumburg et al.1977).

1981: The identification of VLCFA as a biomarker for ALD led to the development of a diagnostic test for ALD based on the demonstration of elevated levels of VLCFA in cultured skin cells (fibroblasts), plasma, red blood cells and amniocytes (Moser et al. 1981). These tests have permitted precise postnatal and prenatal diagnosis. Metabolic studies demonstrated that VLCFA are metabolized (through beta-oxidation) exclusively in subcellular organelles called peroxisomes and this oxidation of VLCFA is reduced in fibroblasts from ALD patients (Singh et al 1981). Therefore, ALD is a peroxisomal disease.

1981: The ALD locus was mapped to the terminal segment of the long arm of the X-chromosome, Xq28 (Migeon et al. 1981).

1982: The first bone-marrow transplantation (BMT) was performed in a boy with cerebral ALD. An allogeneic BMT from a normal HLA identical sibling donor was performed in a 13-year-old boy with rapidly progressive ALD. Engraftment and complete hematologic recovery occurred within 4 weeks. Ten days after BMT, the white blood cell VLCFA levels and enzyme activity became normal; after 3 months, there was progressive reduction of plasma VLCFA to levels only slightly above normal. But neurologic deterioration continued. The patient died of an adenovirus infection 141 days after BMT.

1986: Rizzo et al. demonstrated that the addition of oleic acid (C18:1) to the tissue culture medium normalizes the levels of saturated VLCFA in cultured skin fibroblasts from ALD patients. These findings formed the basis for the development of Lorenzo’s oil. Treatment of ALD patients with Lorenzo’s oil normalizes plasma VLCFA levels within 4 weeks (Moser et al. 1987). Several open-label trials have shown that Lorenzo’s oil failed to improve neurological or endocrine function nor did it arrest the progression of the disease. Unfortunately, the clinical efficacy of Lorenzo’s oil has never been evaluated in a proper placebo-controlled clinical trial. In 2001, Prof Hugo Moser wrote: “It is our view that Lorenzo’s oil therapy is not warranted in most patients who already have neurologic symptoms. The clinical benefit of Lorenzo’s oil is limited at best“.

1990: The team of Prof. Patrick Aubourg reported on the first successful bone-marrow transplantation (BMT) (Aubourg et al. 1990). They had transplanted an 8-year old boy with mild neurological, mild neuropsychological and mild MRI abnormalities. His unaffected non-identical twin was the donor. The patient recovered completely and the neurological, neuropsychological and MRI abnormalities disappeared. When conducted at the earliest stage of cerebral demyelination, a bone-marrow or hematopoietic stem cell transplantation (HSCT) can stabilize or even reverse cerebral demyelination in boys or adolescents with ALD.

1993: A team led by Drs. Mandel and Aubourg identified the putative gene for ALD (ABCD1) using positional cloning strategies (Mosser et al. 1993). The identification of the ALD gene enabled the detection of disease causing mutations, prenatal diagnosis and accurate carrier testing.

1997: Three laboratories reported the generation of a mouse model for ALD (Forss-Petter et al. 1997Kobayashi et al. 1997Lu et al. 1997). While the ALD mouse exhibits the same biochemical abnormalities as observed in patients, the mouse does not develop ALD (Pujol et al. 2002).

1999: The ALD database was created by Hugo Moser and Stephan Kemp. Initially it served only as a registry for mutations identified in the ABCD1 gene, but soon thereafter it was expanded to provide information on many aspects of ALD.

2001: It was reported and established that ALD affects all ethnic groups and it is the most common peroxisomal disorder with an estimated incidence of 1:17,000 (males and females combined) (Bezman et al. 2001). This makes ALD the most common inherited leukodystrophy.

2005: Biochemically, ALD is not only characterized by a defect in the breakdown of VLCFA in peroxisomes, but there is also an increase in the subsequent chain-elongation of VLCFA (Kemp et al. 2005).

2006: The team led by Dr. Ann Moser developed a high-throughput VLCFA analysis method (with C26:0-lysoPC as the diagnostic metabolite) to be used on dried blood spots (Hubbard et al. 2006). These advancements in VLCFA screening will allow the addition of ALD to newborn screening programs.

2009: The team led by Drs. Cartier and Aubourg reported on the successful treatment of two 7-year old boys with early signs of cerebral ALD using gene therapy (Cartier et al. 2009). Brain MRI scans and cognitive tests showed that progression of the cerebral disease stopped 14-16 months post-treatment. This is comparable with the clinical outcome of HSCT.

2010: TThe research team of Dr. Stephan Kemp established that ALDP transports VLCFA across the peroxisomal membrane. A deficiency in ALDP has two major effects: on the one hand, it impairs peroxisomal degradation of VLCFA, and on the other hand, it raises cytosolic levels of VLCFA. These VLCFA are then further elongated to even longer fatty acids by ELOVL1, the human C26 specific elongase (Ofman et al. 2010).

2014: In the United States, New York State started newborn screening for ALD (Vogel et al. 2015). Early diagnosis of ALD is the key to saving lives, because newborn screening allows prospective monitoring and early intervention.

2015: In the US, Connecticut initiated ALD newborn screening. In Europe, the Netherlands expanded its national newborn screening program from 17 to 31 conditions, including ALD.

2016: On February 16, ALD was added to the United States Recommended Uniform Screening Panel (RUSP). In the US, California initiated ALD newborn screening. Since then other states and countries have started newborn screening programs, or have initiated processes intended to add ALD to their existing newborn screening program. Detailed and up-to-date information on ALD newborn screening can be found at the newborn screening page.

 

Experimental Ebola Vaccines Elicit Year-Long Immune Response

 

Results from a large randomized, placebo-controlled clinical trial in Liberia, published online in the October 12 issue of the New England Journal of Medicine, showed that two candidate Ebola vaccines pose no major safety concerns and can elicit immune responses by one month after initial vaccination that last for at least one year. The findings are based on a study of 1,500 adults that began during the West Africa Ebola outbreak. The trial is being conducted by a U.S.-Liberia clinical research collaboration known as the Partnership for Research on Ebola Virus in Liberia (PREVAIL), established in 2014 in response to the request from the Liberian Minister of Health to the U.S. Secretary of Health and Human Services. The trial is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH) and involves scientists and clinicians from Liberia and the United States.

 

PREVAIL conducts collaborative biomedical research in accordance with best practices, to advance science, strengthen health policy and practice, and improve the health of people in Liberia and around the world. The partnership launched this first study, PREVAIL 1, in February 2015. Originally designed to enroll 28,000 volunteers, the trial was scaled back to a Phase 2 study when the decline in new Ebola cases made it impossible to conduct a large efficacy study. The authors stated that “In Liberia, we have demonstrated to the global community that rigorous scientific research can take place in a developing sub-Saharan African country when a mutually beneficial partnership is developed, and that the work of PREVAIL, ranging from the Ebola vaccine to the Ebola survivor studies, clearly manifest the prospects of such a sustainable partnership and clinical research platform.“

 

The vaccine candidates included cAd3-EBOZ, co-developed by NIAID’s Vaccine Research Center and GlaxoSmithKline (GSK); and rVSV-ZEBOV, which was initially engineered by scientists from the Public Health Agency of Canada and is now licensed to Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., (Merck). GSK and Merck provided the test vaccines for the study.

 

From Feb. 2, 2015, through April 30, 2015, the trial rapidly enrolled men and women ages 18 and older with no reported history of Ebola virus disease at Redemption Hospital in Monrovia. Three groups of 500 volunteers received one of the vaccine candidates or a placebo (saline injection). Participants provided blood samples before vaccination and again at one week, one month, six months and one year post-vaccination. Investigators then tested each of these samples for antibodies to the Ebola virus. Responses at one week were modest with both vaccines. However, by one month, 71% of cAd3-EBOZ recipients and 84% of rVSV-ZEBOV recipients developed an antibody response compared to 3% of placebo recipients. At one year, antibody responses were largely maintained in both groups: 64% of cAd3-EBOZ recipients and 80% of rVSV-ZEBOV recipients had an antibody response compared with 7% of placebo recipients.

 

Some participants who received the investigational vaccines experienced mild to moderate side effects that resolved, such as headache, muscle pain, feverishness and fatigue. Overall, investigators did not identify any major safety concerns related to the vaccines. Most of the serious medical issues reported during the trial were due to malaria.

 

Interestingly, at the beginning of the trial investigators found that 4% of participants already had a certain threshold of Ebola antibodies, indicative of past Ebola infection, but no known history of Ebola virus disease. Investigators also found unexpectedly that the proportion of participants developing malaria by one year was lower for participants who received the investigational vaccines as compared with those receiving placebo, particularly among the rVSV-ZEBOV recipients. Future studies are needed to determine if this is a chance finding or if it has some significance related to cross-reactive immunity.

 

Ovarian Reserve Tests Fail to Predict Fertility

 

As a woman ages and her egg supply declines, cells in the ovary secrete lower amounts of inhibin B and anti-Mullerian hormone, substances considered to be indicators of ovarian reserve. The ovaries also produce higher amounts of follicle stimulating hormone (FSH) in the days before ovulation. Although there is little research to support their use, tests for anti-Mullerian hormone are routinely offered in many fertility clinics on the assumption that women with a lower ovarian reserve would be less likely to respond to treatment. Moreover, home fertility tests of urinary FSH are commercially available.

 

According to a study published online in the Journal of the American Medical Association (10 October 2017), tests that estimate ovarian reserve, or the number of a woman’s remaining eggs, before menopause, do not appear to predict short-term chances of conception. According to the NIH, the study suggests that testing for biomarkers of ovarian reserve does not predict the chances for conception in older women still of reproductive age.

 

The study enrolled 750 women from 30 to 44 years of age who had been attempting to conceive for three or fewer months. Women were ineligible to participate if they had known fertility problems, such as polycystic ovarian syndrome, tubal blockage or endometriosis. The women provided a urine and blood sample and checked for conception with home pregnancy test kits. The authors statistically corrected for factors known to reduce fertility, such as smoking, recent use of oral contraceptives and obesity. After six cycles of attempting to conceive, results did not differ significantly between women with low levels and normal levels of anti-Mullerian hormone — a 65% chance of conception, compared to a 62% chance. Similarly, results were not statistically different after 12 cycles: 82% versus 75%. Chances for conception also did not differ significantly according to high versus normal levels of FSH, with conception rates of 61% versus 62% after six cycles and 82% versus 75% after 12 cycles. The authors found no association of inhibin B levels and conception after six cycles or 12 cycles.

 

The authors concluded that the study suggests that younger women with biomarker levels indicating lower ovarian reserve should not become anxious that they won’t be able to have a baby.

 

ONCOLOGY

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NIH Partners With 11 Leading Biopharmaceutical Companies to Accelerate Development of New Cancer Immunotherapy Strategies

 

New immunotherapies have resulted in dramatic responses in certain cancer cases. They have also been the focus of intense investment by biopharmaceutical companies seeking to provide new options for patients who do not respond to other cancer therapies, but they don’t work for all patients. Development and standardization of biomarkers to understand how immunotherapies work in some patients, and predict their response to treatment, are urgently needed for these therapies to provide benefit to the maximum number of people.

 

The National Institutes of Health and 11 leading biopharmaceutical companies today launched the Partnership for Accelerating Cancer Therapies (PACT), a five-year public-private research collaboration totaling $215 million as part of the Cancer Moonshot. PACT will initially focus on efforts to identify, develop and validate robust biomarkers — standardized biological markers of disease and treatment response — to advance new immunotherapy treatments that harness the immune system to attack cancer. The partnership will be managed by the Foundation for the National Institutes of Health (FNIH), with the Food and Drug Administration serving in an advisory role.

 

PACT will facilitate systematic and uniform clinical testing of biomarkers to advance our understanding of the mechanisms of response and resistance to cancer therapy. The research conducted under the partnership will also integrate immune and other related oncology biomarkers into clinical trials by defining a set of standardized biomarkers to be tested across a variety of studies. This approach will allow for consistent generation of data, uniform and harmonized assays to support data reproducibility, comparability of data across trials, and discovery and validation of new biomarkers for immunotherapy and related combinations. PACT will also facilitate information sharing by all stakeholders to better coordinate clinical efforts, align investigative approaches, reduce duplication and enable more high-quality trials to be conducted.

 

PACT partners include AbbVie, Amgen, Boehringer Ingelheim Pharma, Bristol-Myers Squibb, Celgene Corporation, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceutical Companies, Novartis Institutes for Biomedical Research, and Pfizer. Additional support has been provided by the Pharmaceutical Research and Manufacturers Association (PhRMA). The 11 partner organizations will contribute up to $1 million per year for five years through the FNIH for a total private sector contribution of $55 million. NIH will contribute $160 million over the five years of the partnership, pending availability of funds.

 

ABOUT THE FOUNDATION FOR THE NATIONAL INSTITUTES OF HEALTH (FNIH): The FNIH creates and manages alliances with public and private institutions in support of the mission of the NIH. The FNIH works with its partners to accelerate biomedical research and strategies against diseases and health concerns in the United States and across the globe. Established by Congress in 1990, the FNIH is a not-for-profit 501(c)(3) charitable organization. For additional information about the FNIH, please visit <fnih.org>.

 

Expanded Access: FDA Describes Efforts to Ease Application Process

 

The following was extracted from FDA Voice and posted on October 3, 2017.

 

FDA has a long history of supporting patient access to investigational new treatments. This includes working with drug and device companies through the clinical trial process that may lead to FDA approval of the treatment. FDA also offer expanded access programs that provide investigational drugs and devices to patients with serious conditions (generally prior to product approval), when there is no therapeutic alternative.

 

Each year, FDA receives over 1,000 applications for the treatment of patients through expanded access, also known as compassionate use, and the agency authorizes the vast majority (about 99%). FDA recognizes that time is critical for these seriously ill patients who do not have alternative therapies, and who cannot take part in a clinical trial of an investigational therapy. Submissions are usually authorized quickly, often in a matter of days. In the case of emergencies, FDA will typically provide authorization over the phone in a matter of hours. In an effort to eliminate potential hurdles that might delay or even discourage applications, FDA streamlined the expanded access process by introducing a new application form which a physician may use to request expanded access for their patient. Form FDA 3926 reduced the number of required information fields and attachments, and is estimated to take only 45 minutes for a physician to complete. Before expanded access can occur, the drug company must decide whether or not to provide the product. FDA cannot require a manufacturer to provide a product.

 

FDA is lifting another potential burden for physicians who apply to FDA to use an investigational drug to treat their patient. Prior to treating a patient under expanded access, the physician must obtain approval from the Institutional Review Board (IRB) at their facility. This is an important step to protect the rights, safety and well-being of human subjects in clinical research – but assembling the full board may cause delays because it may not routinely meet. As part of a plan to simplify the process for physicians seeking access to an investigational product to treat their patient, FDA has announced that just one IRB member – the chair or another appropriate person – can now approve the treatment. Dr. Gottlieb, FDA Commissioner, believes the simplified IRB process will facilitate access while still protecting patients.

 

More simplifications and clarifications are also in the pipeline. FDA has seen some reluctance among companies to provide investigational drugs for expanded access. This may have been due, in part, to uncertainty about how data for adverse events that occur during treatment under expanded access are viewed by FDA. Companies have voiced concerns that any apparent negative effects might jeopardize the product’s development. FDA recognizes that patients receiving expanded access are usually treated outside of a controlled clinical trial setting. As a result, they may have more advanced disease than clinical trial participants, be receiving other drugs at the same time, and have other diseases. FDA recognizes that these factors make it more difficult to determine the cause an adverse reaction. To clarify how adverse event data in these circumstances are viewed, FDA has updated the guidance for industry entitled, ?Expanded Access to Investigational Drugs for Treatment Use: Questions and Answers’ (questions 25 and 26). The guidance clarifies that suspected adverse reactions must be reported “only if there is evidence to suggest a causal relationship between the drug and the adverse event.“ Dr. Gottlieb is confident these changes will help to address recent issues raised by the Government Accountability Office (GAO), which said that FDA “should further clarify how adverse event data are used.“ FDA is still evaluating the GAO recommendations to identify other possible ways to respond to their concerns.

 

FDA is committed to helping patients and physicians fully understand the expanded access process. Dedicated staff in the Office of Health and Constituent Affairs and CDER’s Office of Communications, Division of Drug Information, already assist physicians and patients in navigating this system. FDA issued three final guidance documents last year to clarify and explain the process. This past July, FDA collaborated with the Reagan-Udall Foundation, patient advocacy groups, the pharmaceutical industry, and other federal agencies to launch a new online tool called the Expanded Access Navigator. This includes a directory where companies can submit public links to their expanded access policies, the criteria used by companies to determine whether to make a drug available through expanded access, and contact information. The directory offers patients and physicians a helpful starting point for researching available investigational therapies. In addition, FDA is working with the Reagan-Udall Foundation to expand this new tool. FDA is pleased to announce that Reagan-Udall will expand its portfolio to include FDA’s Rare Disease Program, with the goal of promoting more expanded access to treatments for rare disorders.

 

Manhattan Seafood Medley with Amazing Sauce

The success of this entree begins by making sure you buy the freshest seafood from a trusted fishmonger and spending the time to collect all the spices needed to give the sauce its rich depth. Make the sauce the day before you serve it and the herbs and spices will infuse my entire recipe, even more. Instead of serving the seafood and amazing sauce over rice or cous cous or potato or quinoa, I chose orzo, which worked wonderfully well. My second choice would have been either cauliflower rice or mashed cauliflower. ©Joyce Hays, Target Hays, Target Health Inc.

 

If you make the sauce the night before, as easy as that is, there’s practically nothing to do the next day, except cook the orzo (or your choice) in chicken stock or broth, and fry the seafood quickly in a very hot skillet. Because this fragrant recipe is impressive and attractive, your family and/or your dinner guests will regard you as a top chef. Try it. As long as there are no allergies or other reasons not to eat seafood, your complements will come rolling in. ©Joyce Hays, Target Health Inc.

 

Dinner for Two

Seafood Ingredients

1/2 pound shrimp, shelled, deveined & cleaned

1/2 pound sea scallops

1 glug extra virgin olive oil

2 or 3 fresh garlic cloves, mashed right in skillet, with a fork, or use a garlic press

Amazing Sauce

2 Tablespoons extra virgin olive oil

2 Tablespoons butter

1 cup chopped onion

2 scallions, chopped

1/2 cup chopped green bell pepper

10 gloves garlic, sliced

1 cup diced ripe tomatoes with a little of their juice

One 28 ounce can of Cento San Marzano Certified Peeled Tomatoes with Basil Leaf

2.5 Tablespoons dry oregano

1/2 teaspoon dried thyme

1 Tablespoon chickpea flour

1 cup clam juice in the bottle

1 Tablespoon Cento tomato paste

1/2 cup cream sherry

1/2 cup heavy cream

2 teaspoons Worcestershire sauce

2 dashes Tabasco

1 pinch Salt

1 pinch black pepper

1 pinch chili flakes

1 teaspoon curry powder

1 Tablespoon flax seeds

1 cup fresh cilantro, well chopped

Keep some chicken stock or broth handy, while cooking the sauce.

2 Tablespoons chopped fresh parsley (save some for garnish)

 

I bought all the ingredients from the following: Whole Foods, FreshDirect, Dean & Deluca, Amazon, Sherry-Lehmann Wines and Spirits. ©Joyce Hays, Target Health Inc.

 

Directions

Make Amazing Sauce the Day Before Serving

1. Do all of the chopping, slicing, cutting now so all sauce ingredients will be ready.

 

Do all your chopping, slicing, cutting at once, on one board. ©Joyce Hays, Target Health Inc.

 

2. Melt olive oil with butter in a large skillet, that has a cover that fits well, over a medium flame.

3. Next, saute the scallions, onion, garlic, pepper, until soft.

 

Saute the scallions, garlic, onion, pepper first. ©Joyce Hays, Target Health Inc.

 

4. Stir in the can of Cento tomatoes and juice, along with the fresh tomatoes. Add the fresh, cut tomatoes

 

Cento tomatoes and fresh tomatoes have been added. ©Joyce Hays, Target Health Inc.

 

5. Add oregano, thyme and all spices, as well as all herbs and flax seeds. Lower heat and cook for 2 or 3 minutes. Sprinkle with the chickpea flour and stir well.

6. Add 1 cup clam juice and cook for 2 to 3 minutes more.

7. Add the Cento tomato paste and stir until blended.

 

All spices and herbs, plus Cento tomato paste, have been added. ©Joyce Hays, Target Health Inc.

 

8. Add the Cream Sherry, Worcestershire, 1/3 cup of heavy dairy cream and Tabasco. Stir well to combine all ingredients. If you feel sauce is too thick, slowly add some chicken stock, stir and determine if you need more. If you think sauce is too thin, very slowly, add more chickpea flour, stirring constantly, until you get the consistency you want.

 

As you can see all final liquids have been added and am ready to stir well to combine everything before simmering for 10 minutes. ©Joyce Hays, Target Health Inc.

 

9. Once all sauce ingredients have been combined, put the tight-fitting cover on and lower the heat to simmer. Allow the sauce to simmer for 10 minutes, then remove from heat. Keep sauce covered and let it cool down to room temperature. Then put in refrigerator overnight.

 

Finally, cover and simmer for 10 minutes. ©Joyce Hays, Target Health Inc.

 

 

On the day of serving

  1. Follow directions on box and make the orzo (or whatever you chose to serve the seafood and amazing sauce over): I like to use chicken stock or broth to cook in, instead of water, which is always part of the directions on the box. After cooking, keep warm.

 

Orzo cooked in chicken stock or broth. ©Joyce Hays, Target Health Inc.

 

2. At this point, when you’re about to serve in 10 minutes, over a low flame, heat up the amazing sauce, so it’s ready when the seafood is done.

 

Warming up the sauce. ©Joyce Hays, Target Health Inc.

3. Seafood, add one glug of extra virgin olive oil in a large skillet over medium heat and with a fork, mash the garlic. If you have a garlic press, you can use that also. Turn the heat up.

4. To the pan, add the sea scallops and shrimp. Allow them to cook for a full minute, check to see if the scallops have turned a light brown. At that point, turn shrimp and scallops over and let the other side turn a light brown. This should take about 1 minute on each side, over a high flame. When done, remove from heat and set aside. At this point, you’re ready to serve.

 

Call me fussy, but I like to cook shrimp and scallops separately, so while I’m trying to get the scallops just right on the outside, I don’t overcook the shrimp. If either is overcooked, they get rubbery and really do taste overcooked which would ruin the whole dish. ©Joyce Hays, Target Health Inc.

 

Cooking the shrimp. ©Joyce Hays, Target Health Inc.

 

5. Spoon the amazing sauce into individual large pasta-shape bowls and place a portion of orzo (or your choice) in the center of each pasta bowl, over the sauce.

6. Spoon seafood over the orzo and the sauce. Add more sauce if desired, sprinkle some chopped parsley over the top, serve and enjoy!

 

All this dinner needs is a fresh crispy salad, your favorite warm bread or rolls to sop up the sauce and an icy white wine.

 

For dessert we had an easy to make fresh berry mousse.

 

Just a little sauce left over, but that’s about it. This is so-o delicious. ©Joyce Hays, Target Health Inc.

 

Finally, Fall is in the air, here in the Big Apple. ©Joyce Hays, Target Health Inc.

 

We are deeply disturbed by all the climate change catastrophes taking place around the world. In our hemisphere we’ve had disasters in: Puerto Rico, Mexico, California, Texas, Florida, as well as ruinous flooding along the whole eastern coast of the U.S.

 

Climate change is the most dangerous global challenge we all have to contend with.

 

Let us give up part of our tribal allegiances, and become world citizens working together toward one goal — saving our planet.

 

From Our Table to Yours

Bon Appetit!