Manuscript on Direct Data Entry (DDE) Accepted for Publication in DIA Journal

 

Target Health is pleased to announce that The Drug Information Journal has accepted a manuscript for publication entitled “Lessons Learned From a Direct Data Entry (DDE) Phase 2 Clinical Trial Under a US IND.” This is the 4th article in a series of articles in the DIA Journal co-authored by Dr. Jules T. Mitchel, addressing approaches to transform clinical trials operations, source document verification and data collection. Two of the 4 articles have already been published.

 

The article assesses the impact of direct data entry (DDE; real time data entry at the time of the patient visit) when used in a Phase 2 study, performed at single site under a US IND. For DDE, the clinical site used Target e*CRF® (EDC) for data collection and Target e*CTR® (eClinical Trial Record) as the subject’s eSource record. Access to Target e*CTR, which is controlled by the PI, was through the Target e*CTR Viewer™. The monitoring plan defined the scope of source document verification (SDV), online data review and the criteria for when to perform onsite monitoring. As a result of DDE, there was a major reduction in onsite monitoring compared to comparable studies that use paper source records; compliance issues were identified in real time and corrected; there was rapid detection of safety issues; and the clinical site saved 70 hours of labor by not using paper source records. We will let you know when it is published or we can send you more details now upon request.

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at www.targethealth.com

Drug Clears Chronic Urinary Infections in Mice

 

 

Scientists have found a way to block the “glue” that lets bacteria stick to the walls of the bladder and start a urinary tract infection. In this image, the glue (red, white and blue spheres) and the glue-blocker (yellow spheres) are overlaid on a micrograph of an infected bladder cell (red) filled with bacteria (green). (Credit: Bradley Jones)

 

 

An experimental treatment for urinary tract infections has easily passed its first test in animals, alleviating weeks-long infections in mice in as little as six hours. “This drug can block the spread of the bacteria that cause urinary tract 1) ___ far better than any other previously reported compound,” says senior author Scott J. Hultgren, PhD, the Helen L Stoever Professor of Molecular Microbiology at Washington University School of Medicine in St. Louis. “If it has similar effects in humans, the potential applications would be very exciting.” The compound is a novel derivative of the natural sugar called mannose, making it unlikely to be toxic. Because the body normally directs excess sugars to the kidney for disposal in the urine, the new drug is naturally sent to exactly where it needs to be to treat infections of the urinary 2) ___.

The results appear in Science Translational Medicine.

 

Urinary tract infections mainly occur in women and are one of the most common infections, causing around $1.6 billion in medical expenses every year in the United States. Scientists believe 80% to 90% of these infections are caused by the bacterium Escherichia coli (E. coli). Half of all 3) ___ will experience a urinary tract infection at some point in their lives, and additional recurrent infections will affect 20% to 40% of these women. Doctors currently treat urinary tract infections with 4) ___. But about 10% to 30% of these infections are antibiotic resistant, and resistance is spreading rapidly.

 

Hultgren has shown that the bacteria that cause urinary tract infections create long hair-like fibers on their surfaces that are tipped with a protein that acts like glue. These glue-tipped fibers allow them to cling to receptors on the bladder wall instead of being flushed out by 5) ___. “Binding to host cells is the key event in most bacterial infections because it’s the step that has to be taken before the bacterium can infect the cell,” Hultgren says. The glue also helps bacteria stick to each other in cooperative communities, increasing their resistance to drugs and the immune 6) ___.

 

James W. Janetka, PhD, research assistant professor of biochemistry and molecular biophysics, designed a group of investigational drugs based on information from Hultgren’s research. Scientists call these drugs mannosides because they are derivatives of mannose and block the bacterial glue’s ability to bind to mannose found on the surface of 7) ___ in the bladder. They designed and tested a number of these compounds, and chose one finalist from among the top six candidates.

When scientists fed the most promising drug to mice with chronic urinary tract infections, bacteria levels in their 8) ___ declined much more quickly than in a second group of mice given antibiotics. The mannoside also prevented new infections.

 

“In other tests, when we gave infected 9) ___ the mannoside first, the bacteria became much more vulnerable to treatment with antibiotics,” Janetka says. “But we produced our most exciting results when we used the mannoside and the antibiotics simultaneously. This created a synergistic effect in the mice that could rapidly eliminate even infections by antibiotic-resistant bacterial strains.” Hultgren says it should be much harder for bacteria to develop resistance to the mannoside. “Antibiotics have to get into the bacterial cell to kill it,” Hultgren says. “This gives the bacteria a number of opportunities to resist: They can change their cell walls to make it harder for the antibiotic to get in, or they can destroy the antibiotic after it gets in or pump it back out of the cell. Mannosides bypass those resistance mechanisms because they don’t have to get into the cell.” Hultgren and Janetka are continuing to develop more potent mannosides. They hope to begin human toxicity tests for the drugs late in 2012. If those tests are successful, 10) ___ trials may follow.

 

According to Hultgren, the approach he and Janetka are using to develop the mannosides could be harnessed to treat infections in other parts of the 11) ___, such as ear or kidney infections. “Cells in other parts of the body have different materials on their surfaces, and bacteria that cause infections in those areas will have proteins that are customized to stick there,” he says. “Blocking binding 12) ___ could be helpful in fighting a wide variety of bacterial infections.” Washington University holds a patent on the 13) ___ developed by Hultgren and Janetka. Their interests in these compounds are managed by the Office of Technology Management in accordance with the University’s policies on intellectual property.

 

ANSWERS: 1) infections; 2) tract; 3) women; 4) antibiotics; 5) urine; 6) system; 7) cells; 8) bladders; 9) mice; 10) clinical; 11) body; 12) proteins; 13) mannosides

Urine

 

 

Not only will the text below be fascinating from a historical perspective for our readers, the important update is equally interesting. Joyce Hays, Target Health Inc.

 

Ancient Babylonian and Sumerian physicians first inscribed their evaluations of urine into clay tablets as early as 4,000 BCE. And in ancientGreece, Hippocrates, often called the father of Western medicine, expanded on urine’s importance: “No other organ system or organ of the human body provides so much information by its excretion as does the urinary system.”

 

Urine as a specimen to diagnose infections in 21st century: Urine as a clinical specimen to diagnose infections has been used since ancient times. Many rapid technologies to assist diagnosis of infections are currently in use. Alongside traditional enzyme immunoassays (EIA), new technologies have emerged. Molecular analysis of transrenal DNA to diagnose infections is also a rapidly growing field. The majority of EIAs utilize the detection of excreted sugar compounds of the outer microbial cell-wall shed into the bloodstream and excreted into the urine.

 

Urine as a Specimen: Milleniums ago urine as a diagnostic specimen attracted the attention of early physicians. InEgypt and Aztec cultures, urine was used to disinfect wounds and was rubbed into the skin to treat cuts and burns. In medical papyri (1550 BCE) of ancientEgypt hematuria was described using hieroglyphic symbols. This condition was most probably caused by the worm Schistosoma haematobium that plagued people living along theNileValley.

 

A Greek philosopher, naturalist, and the Roman emperor’s physician, Claudius Galenos (129–200 CE) used the humoral philosophy of ancient Greece which was based on the concept of Hippocrates (460–370 BCE). According to Hellenistic teaching the body is at equilibrium or homeostasis when four juices are in balance. Urine was one of the four pillars of the galenic humoral pathology. Centuries later this teaching was reintroduced inEuropeduring the Renaissance.

 

Urine is an ideal clinical specimen for diagnostics because it is excreted in large quantities and collection does not require invasive methods. When conventional culture remains either negative or unreliable, diagnosis of systemic infectious disease based on the demonstration of bacterial antigens directly from urine has many potential advantages. If the kidneys are intact, the excreted urinary antigens have a lower MW than of albumin (<67 kDa) or for transrenal DNA usually do not exceed 100 bp. Inspection of the color of urine is still useful today. Unusual color comprising practically the whole spectrum of the rainbow is associated with various metabolic or infectious diseases.

 

Red Color, or Hematuria: Hematuria is a condition of the presence of fresh blood in urine. This symptom is found in a great variety of non-infectious disorders but may also occur in relation to common infections, e.g., urinary tract infection (UTI). It may follow the prodromal period (Katayama syndrome) after infection with Schistosoma haematobium. Hematuria may also be a symptom in viral zoonotic infections that may lead to hemorrhagic fever with renal syndrome (HFRS). HFRS are caused by, e.g., Hantaan, Dobrava,Seoul viruses, or other arboviruses, e.g., Yellow Fever Disease, Rift Valley Fever, or tick-borne Crimea-Congo Hemorrhagic Fever, or Dengue virus that may cause Hemorrhagic Fever.

 

Brown Color, or Black Water Fever and Other Infections: Black water fever is a urological manifestation of malaria caused by Plasmodium falciparum. The color of urine turns brownish due to profuse hemoglobinuria. The brownish color of urine could be observed also in cholestasis with jaundice that may occur, e.g., in hepatitis A virus infection or in leptospirosis, a zoonotic disease, caused by the spirochete Leptospira interrogans.

 

Milky Color, or Chyluria: Chyluria, or “milky urine”, is a symptom of the disturbance of lymphatic flow that may be caused by filariasis. A tapeworm, Wuchereria bancrofti, accounts for 90% of human filariasis and is widespread across tropic and subtropic areas.

 

Inflammatory Markers from Urine: A non-specific immune marker, neopterin, produced by human macrophages has been detected from urine as well as blood. This marker was found elevated in several inflammatory diseases and in AIDS. Recently, pro-inflammatory chemokines and cytokines have been studied in urine from patients with pulmonary tuberculosis (TB). Only IP-10 was excreted in the urine in measurable quantities exceeding those of patients without TB.

 

Tests for Histoplasmosis: Progressive disseminated histoplasmosis (PDH) is common in persons with AIDS, and other immunosuppressed patients. The most frequently reported test is the enzyme immunoassay (EIA). This method detects circulating polysaccharides of Histoplasma capsulatum and provides quantification of antigen concentration. Antigenuria is a sensitive laboratory biomarker of Histoplasma clearance and was used to monitor the efficacy of antimycotic treatment. On the other hand, positive urine antigen levels may persist at low levels for months in patients without clinical illness.

 

Streptococcus pneumoniae Polysaccharides in Urine: Despite availability of pneumococcal vaccines, Streptococcus pneumoniae is the number one causative agent of community acquired pneumonia (CAP), sepsis, and meningitis. The diagnostic utility of excreted soluble urine antigen in patients with pneumonia was first described in 1917.

 

Legionella pneumophila Polysaccharides in Urine: Suspicion of nosocomial or community acquired legionellosis warrants immediate diagnosis and differentiation from other pathogens because the infection requires antibiotic treatment different from that used in pneumococcal infection.

 

LAM from Urine to Assist Diagnosis of Tuberculosis: Tuberculosis is a global health emergency of enormous proportions. The major obstacles to TB control is the lack of fast, affordable, and accurate diagnostic techniques both for pulmonary and extrapulmonary TB in adults and children. One approach is to detect the presence of urinary microbial metabolites, e.g., LAM. Lipoarabinomannan is a structural heat-stable cell-wall glycolipid of Mycobacterium tuberculosis. It constitutes up to 15% of the total bacterial weight. LAM is a virulence factor and is released from metabolically active or degrading M. tuberculosis in TB infection.

 

Urine as a Sample to Study Viral Infections: Human polyomaviruses (HPyVs) are widespread and unique to humans. High quantities of viral particles can be shed in urine from a healthy individual. In nephropathy, e.g., after kidney transplantation, in profound immunosuppression or in AIDS, in hemorrhagic cystitis (BKV), or in symptoms of central nervous system compatible with progressive multifocal leucomyelopathy (JCV), these viruses may no longer be “innocent bystanders”. NAATs for both urine and blood have been developed to detect, subtype, and estimate viral loads. Congenital cytomegalovirus (CMV) infection, a leading cause of sensorineural hearing loss and neurological impairment can be robustly detected directly from urine. In primary infections CMV is excreted and can be cultured from urine for several weeks. Urine has also been utilized as sample for the early diagnosis of Dengue virus infection. In some situations urine NAATs provided greater sensitivity than does analysis of plasma. Virus-specific IgG or IgA-class antibodies as serological markers of this disease have been also detected in urine.

 

Urine as a Sample to Diagnose STDs: Urine is extremely useful to diagnose infections of the reproductive tract. The review of non-invasive testing for Chlamydia trachomatis and Neisseria gonorrhoeae showed that both assays reached specificities of 97% for both infections and in both genders.

 

Emerging Technologies and Pathogens: Flow cytometry-based analysis (FACS) that quantifies both bacteria and white blood cells in the urine has emerged as a promising diagnostic tool. Gas chromatography/mass spectrometry to detect volatile organic components in human urine has been recently described although not yet implemented in clinical practice. Detection of microbial transrenal DNA is an attractive option to diagnose infections. As new detection technologies emerge, knowledge about new pathogens continues to increase. For example, Actinobaculum schaalii may cause undiagnosed cystitis predominantly in the elderly and in those persons in whom the primary focus appears to be anomalies in the genitourinary tract (e.g., benign prostatic hyperplasia). Most recently it has been associated with bloodstream infections. Urine FACS may prove useful to identify less known or unknown pathogens which can be suspected on the basis of discrepancy between conventional culture and a positive fluorescence signal denoting “presence” of bacteria.

 

Conclusion: In the future urine, because of ease of collection, processing, and storage, may be extensively used for targeted multiplexed analyses. Current state-of-the-art, however, indicates that some detection methods still require further understanding of molecular forms and structures detected, as well as the excretion kinetics of these polymeric compounds.

 

Citation: Tuuminen T (2012) Urine as a specimen to diagnose infections in twenty-first century: focus on analytical accuracy. Front. Immun. 3:45. doi: 10.3389/fimmu.2012.00045

Survival Advantage for Bypass Surgery Compared With Non-Surgical Procedure

 

Comparative effectiveness research results provide information to help patients and health care providers decide which practices are most likely to offer the best approach for a particular patient, what the timing of interventions should be, and the best setting for providing care.

 

In coronary heart disease (CHD), also called coronary artery disease, plaque builds up inside the coronary arteries that supply blood to the heart muscle. Over time, blocked or reduced blood flow to the heart muscle may occur, resulting in chest pain, heart attack, heart failure, or erratic heart beats. Each year, more than half a million Americans die from CHD.

 

In CABG, or bypass surgery, the most common type of heart surgery in the U.S., blood flow to the heart muscle is improved by using (“grafting”) a healthy artery or vein from another part of the body to bypass the blocked coronary artery. In contrast, in theU.S., cardiologists perform over a million revascularization procedures, also known as percutaneous coronary intervention (PCI), to open blocked arteries in order to improve blood flow to the heart muscle. PCI is a less invasive, non-surgical procedure in which blocked arteries are opened with a balloon (also called angioplasty). A stent, or small mesh tube, is then usually placed in the opened arteries to allow blood to continue to flow into the heart muscle.

 

According to an article published online in the New England Journal of Medicine (27 March 2012), a new comparative effectiveness study found older adults with stable CHD who underwent CABG surgery had better long-term survival rates than those who underwent PCI. While there were no survival differences between the two groups after one year, after four years the CABG group had a 21% lower mortality.

 

With NIH support, the American College of Cardiology Foundation (ACCF) and the Society of Thoracic Surgeons (STS) came together to compare short- and long-term survival outcomes after CABG versus PCI. The investigators linked medical data available in their ACCF and STS databases with follow-up information in the Medicare Provider Analysis and Review database of the Centers for Medicare and Medicaid Services. Linking these three datasets from 644 U.S. hospitals allowed the study to analyze information from the STS database on 86,244 older adults (average age 74) with stable CHD who underwent CABG between 2004 and 2007 and 103,549 older adults (average age 74) with stable CHD from the ACCF database who underwent PCI between 2004 and 2007. Follow-up ranged from one to five years, with an average of 2.72 years.

 

Results showed that at one year there was no difference in deaths between the groups (6.55% for PCI versus 6.24% for CABG). However, at four years there was a lower mortality with CABG than with PCI (16.4% versus 20.8%). This long-term survival advantage after CABG was consistent across multiple subgroups based on gender, age, race, diabetes, body mass index, prior heart attack history, number of blocked coronary vessels, and other characteristics. For example, the insulin-dependent diabetes subgroup that received CABG had a 28% increased chance of survival after four years compared with the PCI group.

 

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Interventions to Prevent Type 2 Diabetes Give Good Return on Investment (ROI)

 

In the U.S, nearly 26 million people have diabetes, and up to 95% of them have type 2 diabetes. About 7 million people have type 2 diabetes but do not know it. In addition, about 79 million adults have prediabetes, with high blood sugar levels that are not yet in the diabetic range. Prediabetes substantially raises the risk for developing type 2 diabetes.

 

According to an article published online in Diabetes Care (19 March 2012), programs to prevent or delay type 2 diabetes in high-risk adults result in fewer people developing diabetes and lower health care costs over time. Prevention programs that apply interventions tested in the landmark Diabetes Prevention Program (DPP) clinical trial would also improve quality of life for people who would otherwise develop type 2 diabetes.

 

In 2002, the DPP showed that lifestyle changes (reduced fat and calories in the diet and increased physical activity) leading to modest weight loss reduced the rate of type 2 diabetes in high-risk adults by 58%, compared with placebo. Metformin reduced diabetes by 31%. As the study monitored participants for seven more years in the DPP Outcomes Study (DPPOS), lower rates of diabetes continued in the lifestyle and metformin groups compared with placebo. Lifestyle changes were especially beneficial for people age 60 and older.

 

The economic analysis of the DPP/DPPOS found that metformin treatment led to a small savings in health care costs over 10 years, compared with placebo. (At present, metformin, an oral drug used to treat type 2 diabetes, is not approved by the FDA for diabetes prevention.) The lifestyle intervention as applied in the study was cost-effective, or justified by the benefits of diabetes prevention and improved health over 10 years, compared with placebo.

 

The DPP enrolled 3,234 overweight or obese adults with blood sugar levels higher than normal but below the threshold for diabetes diagnosis. Participants were randomly assigned to a lifestyle intervention aimed at a 7% weight loss and 150 minutes per week of moderate intensity activity, metformin treatment, or placebo pills. The groups taking metformin or placebo pills also received standard lifestyle recommendations.

 

“We don’t often see new therapies that are more effective and at the same time less costly than usual care, as was the case with metformin in the DPP. And while the lifestyle intervention was cost-effective, we would see greater savings if the program were implemented in communities,” said Griffin P. Rodgers, M.D., director of the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). “This has already been demonstrated in other NIDDK-funded projects, including one in YMCAs, where a lifestyle-change program cost $300 per person per year in a group setting, compared to about $1,400 for one-on-one attention in the DPP.”

 

In the DPP, direct costs over 10 years per participant for the lifestyle and metformin interventions were higher than for placebo ($4,601 lifestyle, $2,300 metformin, and $769 placebo). The higher cost of the lifestyle intervention was due largely to the individualized training those participants received in a 16-session curriculum during the DPP and in group sessions during the DPPOS to reinforce behavior changes.

 

However, the costs of medical care received outside the DPP, for example hospitalizations and outpatient visits, were higher for the placebo group ($27,468) compared with lifestyle ($24,563) or metformin ($25,616). Over 10 years, the combined costs of the interventions and medical care outside the study were lowest for metformin ($27,915) and higher for lifestyle ($29,164) compared with placebo ($28,236). Throughout the study, quality of life as measured by mobility, level of pain, emotional outlook and other indicators was consistently better for the lifestyle group.

 

According to the authors, the DPP demonstrated that the diabetes epidemic, with more than 1.9 million new cases per year in theU.S., can be curtailed. We now show that these interventions also represent good value for the money,” said study chair David M. Nathan, M.D., director of theDiabetesResearchCenteratMassachusetts GeneralHospital,Boston.

 

Weight Loss and Increased Fitness Slow Decline of Mobility in Adults

 

Overweight and obesity affects more than two-thirds ofU.S.adults age 20 and older. More than one-third of adults are obese. Many factors contribute to the problem, including genetics, lifestyle habits, and the food environment. Excess weight can lead to type 2 diabetes, heart disease, high blood pressure, stroke, and certain cancers. Nearly 26 million Americans have diabetes, and 7 million of them do not know it.

 

According to an article published in the New England Journal of Medicine (2012; 366:1209-1217), weight loss and increased fitness slows decline of mobility in adults which could lead to lower health care costs for adults with type 2 diabetes. Results showed that weight loss and increased physical fitness nearly halved the risk of losing mobility in overweight or obese adults with type 2 diabetes.

 

Look AHEAD (Action for Health in Diabetes) trial is a multi-center, randomized clinical trial designed to determine the long-term effects of intentional weight loss on the risk of developing cardiovascular disease in overweight and obese individuals with type 2 diabetes. Beginning in 2001, a total of 5,145 participants were randomly assigned to either an intensive lifestyle intervention group (ILI) or a diabetes support and education group (DSE). Participants receiving the intervention attended group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity. The DSE group attended three meetings each year that provided general education on diet, activity, and social support.

 

To assess mobility and disability, participants rated their ability to carry out activities with or without limitations. Included were vigorous activities such as running and lifting heavy objects and moderate ones such as pushing a vacuum cleaner or playing golf. Participants also separately rated their ability to climb a flight of stairs; bend, kneel or stoop; walk more than a mile; and walk one block. Both groups were weighed annually and completed a treadmill fitness test at baseline, after one year, and at the end of four years.

 

Results showed that after 4 years of the study, participants in theILIgroup experienced a 48% reduction in mobility-related disability compared with the DSE group. Furthermore, 20.6% ofILIparticipants reported severe disability compared to 26.2% of participants in the DSE group. Likewise, 38.5% of those in theILIgroup reported good mobility, whereas the rate was 31.9% in the DSE group. Weight loss was a slightly stronger predictor of better mobility than improved fitness, but both contributed significantly to the observed reduction in risk.

 

According to the authors, the weight loss and physical activity goals promoted in the study are well within the reach of most Americans and that future research is needed to determine if this sort of intervention can be translated into public health interventions, particularly in light of possible effects on health care costs.”

TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area

 

 

FDA Takes Action to Address Tobacco Epidemic

 

The FDA released two separate draft guidance documents to help fight the tobacco epidemic and stop children from using tobacco. The draft guidance documents implement provisions of the Family Smoking Prevention and Tobacco Control Act that will ultimately provide the public with previously unknown information about the chemicals in tobacco products and help prevent misleading marketing about the risks associated with tobacco products.

 

The first document provides guidance on how companies will comply with the requirement to report on the quantities of potentially harmful chemicals in tobacco products. The second document provides guidance to companies that seek to advertise or market a tobacco product as less harmful or associated with reducing the risk of tobacco-related disease.

 

The Family Smoking Prevention and Tobacco Control Act requires tobacco product manufacturers and importers to report quantities of harmful and potentially harmful constituents (HPHCs) found in tobacco products or tobacco smoke by brand and sub-brand. HPHCs are chemicals or chemical compounds in a tobacco product or tobacco smoke that cause, or could cause, harm to smokers or non-smokers. All HPHCs included on the list cause or may cause serious health problems including cancer, lung disease, and addiction to tobacco products.

 

While there are more than 7,000 chemicals in tobacco and tobacco smoke, FDA has established a list of 93 HPHCs that tobacco companies will be required to report for every regulated tobacco product sold in theUnited States. The FDA recognizes that industry may be unable to meet the deadline due to current testing limitations. In recognition of this, the draft guidance released today identifies 20 HPHCs that are representative of the full list and for which testing methods are well established and widely available.

 

FDA intends to focus reporting enforcement on these 20 HPHCs during 2012 and intends to make information about the amount of HPHCs in specific products available to the public in a consumer-friendly format by April 2013.

 

FDA also issued draft guidance on submitting applications to sell modified risk tobacco products (MRTPs). Modified risk tobacco products are tobacco products that are sold, distributed, or marketed with a claim to reduce harm or the risk of tobacco-related disease.

 

The Tobacco Control Act establishes rigorous scientific criteria an applicant’s tobacco product must meet before FDA can allow the applicant to sell that product with a claim to reduce harm. The draft guidance describes scientific studies and analyses an applicant should submit to demonstrate its product will, or is expected to, significantly reduce harm or exposure to individuals, and benefit the health of the population as a whole.

 

The draft guidance for MRTPs provides details for those who seek to market a tobacco product as modified or lower risk including how to organize and submit an MRTP application, what scientific studies and analyses should be submitted, and what information should be collected through post-market surveillance and studies.

 

The draft guidance document and a December 2011 report from the Institute of Medicine (IOM) titled “Scientific Standards for Studies on Modified Risk Tobacco Products” are open for comments from the public until June 4, 2012. Before issuing the final guidance, FDA will consider these public comments, the IOM report and feedback from an FDA public workshop held in August 2011.

“Cheaper is Better”: Another Challenged Shibboleth

 

 

By Mark L. Horn, MD, MPH, Chief Medical Officer, Target Health Inc.

 

With oral arguments at the Supreme Court, the multistate challenges to the Affordable Care Act are hogging the headlines. However, interesting and substantive discussions about key elements of healthcare spending and quality continue apace, and it’s important to headline these, especially when they challenge conventional wisdom in ways that suggests “truths” widely accepted with profound implications for health policy may, in fact, be more nuanced than we think. It’s especially important to pay attention to these challenges when they have significant impact on health policy makers.

 

The March 14th issue of JAMA contains an article (Stukel, Fisher, Alter et.al. JAMA 2012; 307:1037-1045) and an accompanying editorial (Joynt & Jha. JAMA 2012; 307:1082-1083), examining the relationship between health care quality and cost. For some time, it’s been almost an article of faith that not only can quality be achieved with lower costs, but that there is, counter-intuitively, potentially an inverse relationship between these parameters. Based upon data from the Dartmouth Atlas, it has been suggested that (at least for the Medicare population) higher spending might, paradoxically, negatively impact health outcomes.

 

The recently published article and editorial cite evidence suggesting that theseDartmouthdata should be interpreted in a more nuanced fashion, that the poor outcomes potentially result from dysfunctional care systems and that institutions thoughtfully targeting increased resource allocation may indeed improve patient outcomes.

 

These two papers are important because of their challenge to a shibboleth with appeal to both sides of the health care debate – the entrenched idea that costs can be cut without compromising quality, the quintessential ‘free lunch’. Unfortunately, as with most things medical, it’s not so simple. Cost cutting must be done with care to assure that it is the dysfunctional systems and ineffective care that are cut, while spending on improving coordination and enhanced application of evidence based interventions, including subspecialty care and procedures, may well improve outcomes. It’s impossible to know how all this will ‘net out’ in dollar terms, but there is clearly a developing literature supporting the argument that the burden of providing data and analyses confirming the salutary impact of their decisions will (and should) increasingly fall upon the costs cutters. Policymakers will, and should, be compelled to justify their cost cutting recommendations with evidence.