Webinar tackles the tribulations of investigator initiated trials

Investigators should be careful to distinguish between interventional and observational studies when developing investigator initiated trials (IITs) because the distinction can effect billing strategies and budget, according a Health Care Compliance Association (HCCA) webinar, presented by Liz Christianson and David Russell of PFS Clinical. The webinar addressed key areas of focus for developing IITs, including protocol development, industry funding, and regulatory requirements.


Christianson noted there has been a remarkable renewed interest in IITs in the last two years, due largely due to industry sponsors realizing that IIT relationships are symbiotic. However, despite the renewed focus, IITs present challenges. In some cases, challenges arise from the fact that 85 percent of investigators have participated in only one clinical trial in their careers.


Protocol development is important, particularly with respect to the articulation of an IIT as interventional or observational. Christianson noted that from reading the protocol it should be obvious whether an IIT is interventional or observational because the distinction can have significant downstream effects on budgets and billing. Christianson defined observational studies as trials where the investigator makes no intervention and allocates treatment based upon clinical decisions. She distinguished this from interventional studies, where participants are assigned to receive one or more interventions (or no intervention) so researchers can evaluate the effects of the interventions on health outcomes.


Because Medicare uses set criteria for reimbursement of trials, the objective language can be crucial to reimbursement. In observational studies, study actions should not be able to be linked to specific claims codes. Conversely, in an interventional study, actions should be linked to a specific billing code. Thus, the objective language in a study should clearly indicate what the PI’s true intent is—to treat with routine care, then collect patient data (observational) or to assign patients to specific treatment groups (interventional).


Russell discussed the registration of trials on ClinicalTrials.gov. All applicable clinical trials must be registered on the website in order to receive a unique National Clinical Trial (NCT) number, which is required on all CMS claims. Russell also covered specific data elements and registration information required by the September 21, 2016, Final rule for clinical trials (81 FR 64982). Russell reminded responsible parties that trials must be registered no later than 21 days after enrollment of the first participant and, at minimum, the applicable clinical trial must be updated every 12 months. Summary results (including adverse even information), must be submitted not later than one year after a trial’s primary completion date.

Wolters Kluwer Holiday

We will not be posting September 1 or September 4 due to Labor Day. The Wolters Kluwer Legal and Regulatory U.S. Health Law Editorial Team wishes you a safe and happy holiday. We will resume our regular posting schedule on Tuesday, September 5.

Fish advice issued for women and parents of young children

Fish and shellfish provide protein, are low in saturated fat, are rich in many micronutrients, and provide certain omega-3 fatty acids. However, as a result of natural processes and human activity, fish also contain mercury in the form of methylmercury. Methylmercury can adversely affect the central nervous system, particularly the developing brain of the fetus. As a result, women who are pregnant or may become pregnant, as well as breastfeeding mothers and parents of young children, need information to make informed choices when it comes to fish that are healthy and safe to eat.

In June 2014, the FDA and the U.S. Environmental Protection Agency (EPA) jointly released a draft update to a March 2004 document entitled “What You Need to Know About Mercury in Fish and Shellfish.” The agencies have now announced revised fish advice that contains advice and supplemental questions and answers for those who want to understand the advice in greater detail. The fish advice contains a reference chart that sorts 62 types of fish into three categories:

  • Best Choices (36 types of fish)
  • Good Choices (19 types of fish)
  • Choices to avoid (7 types of fish: King mackerel, Marlin, Orange roughy, Shark, Swordfish, Tilefish (Gulf of Mexico), and Tuna (bigeye))

The reference chart suggests that women of childbearing age (16-49 years old), especially pregnant and breastfeeding women, and parents and caregivers of young children should observe the following guidelines:

  • Eat two to three servings of fish a week from the Best Choices list or one serving from the Good Choices list.
  • Eat a variety of fish.
  • Serve one to two servings of fish a week to children, starting at age two.
  • If you eat fish caught by family or friends, check for fish advisories. If there is no advisory, eat only one serving and no other fish that week.

The recommended serving size for an adult is four ounces. For children age four to seven, the recommended serving size is two ounces.

How were fish categorized?

The agencies note that they took a cautious and highly protective approach in determining which fish belonged in each category. They calculated how many servings the average pregnant woman could eat in a week using information on mercury content of each fish type from FDA’s database for commercial fish and other sources. If she could eat that fish at least three times a week, then they listed it in the “Best Choices” category. If she could eat that fish only once a week, or twice but not three times a week, then they listed it in the “Good Choices” category. If she could not eat a serving of that fish once a week, then they listed the fish in the “Choices to Avoid” category.

Why are some fish in more than one category?

The agencies explain why tuna and tilefish appear in multiple categories on the chart. Tuna comes in different types (or species), such as albacore, bigeye, and yellowfin. And because some types of tuna that are bigger or live longer tend to have higher mercury levels, they are in different categories. For example, canned light tuna is in the Best Choices category. Albacore (or white) tuna and yellowfin tuna are in the Good Choices category, and bigeye tuna is in the Choices to Avoid. In addition, fish of the same species that are caught in different geographic locations can vary in mercury content. For example, tilefish are in two categories because tilefish in the Gulf of Mexico have higher mercury levels than those in the Atlantic Ocean. As such, Gulf of Mexico tilefish is in the Choices to Avoid and Atlantic Ocean tilefish is in the Good Choices.

If some species of fish are not on the reference chart, such as mussels, that means the agencies did not have enough reliable mercury data to include it.


Highlight on Colorado: 2016 report on effects of marijuana legalization

On November 8, 2016, nine states will have legalization of marijuana for either medical or recreational use on the ballot. Five of those states will consider the recreational use of marijuana, including California, Massachusetts, Maine, Arizona, and Nevada. Before these states “go to pot,” perhaps they should consider the results of a 2016 study by the Colorado Department of Public Safety.

The study was mandated by the Colorado General Assembly. It required the Division of Criminal Justice in the Colorado Department of Public Safety to conduct a study of the impacts of Colorado’s 2013 legalization, particularly as they relate to law enforcement activities.

Public Safety

The study found that the total number of marijuana arrests decreased by 46 percent between 2012 and 2014, from 12,894 to 7,004. As a share of all arrests in Colorado, marijuana was responsible for 6 percent of all arrests in 2012 and 3 percent in 2014. The number of marijuana arrests decreased by 51 percent for Whites, 33 percent for Hispanics, and 25 percent for African-Americans.

In terms of court filings, the study found that the total number of marijuana-related filings declined 81 percent between 2012 and 2015, from 10,340 to 1,954. The filings fell 69 percent for juveniles 10 to 17 years old, 78 percent for young adults 18 to 20 years old, and 86 percent for adults 21 or older. In terms of organized crime, between 2012 and 2015, there were 88 filings that were related to some marijuana charge. The most common marijuana industry-related crime in Denver was burglary, accounting for 63 percent of marijuana crime related to the industry in 2015.

Traffic safety data was limited, but the study noted that the number of summons issued by the Colorado State Patrol for Driving Under the Influence in which marijuana or marijuana-in-combination with other drugs was involved decreased 1 percent between 2014 and 2015 (674 to 665).

In terms of assessing diversion of marijuana to other states, from January 1, 2014, to August 30, 2015, the study found that there were 261 drug-related interdiction submission in which Colorado was the initiating state. Of those 261 submissions, 169 (65 percent) were for marijuana/hashish.

Public Health

According to the National Survey on Drug Use and Health, administered by the Substance Abuse and Mental Health Services Administration, the current prevalence rates for marijuana usage in the past 30 days have increased significantly for young adults (18 to 25 years old), from 21 percent in 2006 to 31 percent in 2014. Marijuana use by adults (26 years or older) also increased significantly, from 5 percent in 2006 to 12 percent in 2014. In comparison, the study cited a 2014 telephone survey in Colorado that found 14 percent of adults reported marijuana use in the past 30 days and 33 percent of current users reported using daily.

According to the study, hospitalizations with possible marijuana exposures, diagnoses, or billing codes per 100,000 hospitalizations increased from 803 per 100,000 before commercialization (2001-2009) to 2,413 per 100,000 after commercialization to 2,413 per 100,00 after commercialization (2014- June 2015).  The number of calls to poison control mentioning marijuana exposure increased from 44 calls in 2006 to 227 calls in 2015.

Youth Impact

The study noted that in 2013, a Healthy Kids Colorado Survey (HKCS) found that 80 percent of high school students did not use marijuana in the past 30 days. The HKCS showed, however, that marijuana use increased by grade level and that Colorado youth use marijuana at a higher rate then the national average. The perception of health risk of using marijuana is also declining among Colorado youth, according to the HKCS.

The number of juvenile marijuana arrests increased 5 percent, from 3,234 in 2012 to 3,400 in 2014, according to the study. The number of White juvenile arrests decreased from 2,198 in 2012 to 2,016 in 2014 (-8 percent). The number of Hispanic juvenile arrests increased from 778 in 2012 to 1,006 in 2014 (+29 percent). The number of African-Amercian juvenile arrests increased from 205 in 2012 to 324 in 2014 (+58 percent).

The study noted that data on drug tests from the Division of Probation Services showed that the percent of the 10- to 14-year-old group testing positive for tetrahydrocannabinol (THC — the chemical responsible for most of marijuana’s psychological effects) one or two times increased from 19 percent in 2012 to 23 percent in 2014, while the percentage testing positive three or more times went from 18 to 25 percent.

Colorado Department of Education data showed that the drug suspension rates increased from 391 (per 100,00 students) in the 2008-09 school year to 506 in 2009-10. In addition, the drug expulsion rate was 65 in 2008-09, increasing to 90 in 2009-10, and decreasing to 50 in 2014-15.

Revenue Data

The study also noted that in December 2015 there were 2,538 licensed marijuana businesses in Colorado, with 70 percent located in Denver, El Paso, Pueblo, and Boulder. The total tax revenue, licenses, and fees from these businesses increased from $76,152,468 in 2014 to $135,100,465 in 2015 (+77 percent). The excise tax revenue dedicated to school capital construction assistance totaled $35,060,590 in 2015.


The study found that because data was only available through 2014, it was too soon to draw any definite conclusions about the potential effects of marijuana legalization or commercialization on public safety, public health, or youth outcomes. In addition, the study noted that the lack of pre-commercialization data, the decreasing social stigma, and challenges to law enforcement combine to make it difficult to translate the early findings into definitive statements of outcomes.