Thinking about study designs

When learning the designs of research studies, an effective exercise is to look at examples drawn from actual research studies. In this post, we present a series of eight research studies. For each study, the exercise is to classify each study by answering the following questions.

  • Is it an experiment or observational study?
  • If an experiment, what is the experimental design?
  • If an observational study, what is the observational design?
  • If an observational study, discuss why it cannot be conducted as an experiment. What would be the obstacles in setting up the study as an experiment? For example, what are the practical concerns and/or ethical concerns that make conducting experiment not a feasible option?

For basic information about study designs, see the previous post on experiments and observational studies (Design of experiments, Design of observational studies).

Study 1 – Can Exercises Keep Us From Aging?
This study involved mice that were genetically programmed to age quickly. These mice lacked the ability to properly repair genetic mutations to their mitochondria (many scientists consider the loss of healthy mitochondria to be an important underlying cause of aging in mammals).

Researchers led by pediatric professor Dr. Mark Tarnopolsky assigned half the mice to exercise regularly starting at 3 months old. These mice ran on a wheel for 45 minutes at a time three times a week (equivalent to a human running 10K three times a week starting at age 20). The other half of the mice remained sedentary.

Findings of the Study:

  • At 8 months, the running rats remained youthful while the sedentary mice were bald, frail and dying. The running mice had maintained all of their muscle mass and brain volume. Their gonads were normal, as were their hearts. They could balance on narrow rods.
  • At one year, none of the exercising mice had died of natural causes. All of the unexercised mice had died by one year.
  • Even though the running mice still harbored the mutations that should have affected mitochondrial repair, they had more mitochondria over all than the sedentary mice.

Can exercise keep us from aging?
Can exercise keep you young?

Study 2 – The Longevity Project
The study was initiated in 1921 by the psychologist Lewis Terman and was continued by other researchers upon his death in 1956. In 1990, psychologists Howard Friedman and Leslie Martin began their research using the data collected in this project. The study followed the lives of 1500 gifted children in California from about 10 years of age to death.

Terman’s original study was an IQ study (to discern whether it was possible to recognize early glimmers of high potential). Using the extensive data collected by Terman, Friedman and Martin explored how factors such as social connections, personality, religious involvement, marriage and persistence relate to longevity.

Terman collected information about the family background, schooling and other activities of the children in the study (affectionately called Termites). Some of the collected data included the number of books in their houses, how active the children were in their playtime and how happy were the marriages of their parents. Terman also measured the personalities of the children, whether their dispositions were prudent, extroverted or cheerful. When they became adults, Dr. Terman collected additional data about their career choices and their family experiences through follow-up interviews across the years.

Friedman and Martin supplemented the data by obtaining the age and cause of death through death certificates. The results of their research were published in about 50 scholarly papers and were summarized in a book called The Longevity Project.

Many of the findings in The Longevity Project are surprising, results that turn conventional wisdom on its head. They discovered that many common beliefs that promise long life – like marriage, the mindset of don’t worry and be happy, and not working hard – do not associate with long life.

One surprise finding is that optimism is overrated. Cheerful and optimistic people are actually less likely to live long lives. Among the participants in the study, the most cheerful and optimistic children grew up to take more risks. By expecting that only good things would happen in their lives, they predisposed themselves to be heavy drinkers and to engage in other risky behaviors and hobbies.

The study found that some degree of worrying is actually good. The prudent, persistent and hard working participants tended to stay healthier and live longer. This is the most notable finding, that is, conscientiousness is the best personality predictor of long life. The study found that conscientious (careful, sometimes even neurotic but not catastrophizing) people lived the longest. They developed better social relationships and had more career accomplishments. Another finding is that avoidance of stress is a bad advice. The study found that stress did not hurt the participants who had stressful jobs and who had found meaning in their jobs and were committed to them.

The study also found that women thrive post divorce and men don’t. The children in the study who were sent to school one year early tended to have emotional problems that led to unhealthy behaviors and premature death. The study also found that too much exercise can backfire. Being active physically is important. But it is about doing activities that you love rather than adhering to a certain fitness program.

The Longevity Project.

Study 3 – When Exercise Is Too Much of a Good Thing
The goal of the study was to shed light on the question of whether years of intense endurance training might be harmful to the heart.

The study compared a group of 29 male endurance athletes (former British national or Olympic team in distance running or rowing as well as amateur athletes who had run at least 100 marathons) with a group a 20 healthy men over 50 (none of them were endurance athletes). Of the endurance athletes, 12 were aged 50 or older (the oldest one was 67) and the other 17 were relatively young (aged 26 to 40). They had trained and worked strenuously throughout their adult lives even after their active competition years.

Both groups of participants underwent a new type of magnetic resonance imaging of their hearts that can identify very early signs of fibrosis (scarring within the heart muscle). Irregular heart function and heart failure can result if fibrosis becomes too severe.

The researchers found that none of the 17 younger endurance athletes and none of the non-athletes had fibrosis in their hearts. However, half of the older endurance athletes had some fibrosis in the heart muscle. The association between endurance training and fibrosis was very strong. The athletes with fibrosis in heart muscle were the ones who trained the longest and the hardest. The more years of strenuous training or the more marathons completed results were associated with a greater likelihood of heart damage.

When exercise is too much of a good thing.

Study 4 – Marijuana May Impair Thinking While Relieving Other MS Symptoms
Medical marijuana is a potential natural remedy for pain and other symptoms of multiple sclerosis. However, not enough research has been done to see if marijuana actually helps with the symptoms of MS, which affects the brain and spinal cord. Given that MS is associated with cognitive deterioration, the goal of this study was to determine the neuropsychological effects of canabis use in MS patients.

Two groups of MS patients (one had 25 cannabis users and one had 25 non-users) were administered the Minimal Assessment of Cognitive Function in MS battery of neuropsychological tests, the Hospital Anxiety and Depression scale (HADS), and the Structured Clinical Interview for the DSM-IV Axis I Disorders (SCID-I).

The study found that Cannabis users performed significantly more poorly than nonusers on measures of information processing speed, working memory, executive functions, and visuospatial perception. They were also twice as likely as nonusers to be classified as globally cognitively impaired. There were no between-group differences on the HADS measures of depression and anxiety or lifetime SCID-I psychiatric diagnoses.

The researchers concluded that this study provides evidence that prolonged use of inhaled or ingested street cannabis in patients with MS is associated with poorer performance on cognitive domains commonly affected in this population.

This is a study funded by The Multiple Sclerosis Society of Canada.

Marijuana May Impair Thinking While Relieving Other MS Symptoms.

Study 5 – Firefighters and on-duty deaths from coronary heart disease

Coronary heart disease (CHD) has consistently been the leading cause of “on-duty deaths” or fatalities resulting from injury or illness occurring during fire department duties, accounting for 45% of on-duty deaths among United States firefighters. The goal of this study was to identify occupational and personal risk factors associated with on-duty CHD death.

The study compared 52 male firefighters who died while on firefighting duty and whose on-duty deaths were from cardiovascular causes with two reference groups of firefighters: 51 male firefighters who died of on-duty trauma and 310 male active firefighters (firefighters who were examined in 1996/1997 and continued to work professionally as firefighters as of 1998). The data for the 52 on-duty CHD firefighting fatalities were obtained from the National Institute for Occupational Safety and Health.

The study found that the circadian pattern of CHD deaths was associated with emergency response calls: 77% of CHD deaths and 61% of emergency dispatches occurred between noon and midnight. In contrast, in the general population CHD deaths peak between 6 am and noon.

The study found significantly increased risks of CHD deaths during fire suppression; training and alarm response.

The study found that age greater than 45 years, smoking, hypertension, and prior diagnosis of arterial-occlusive disease remained strong independent predictors for on-duty CHD death.

The study concluded that there is strong support that most on-duty CHD fatalities are work precipitated and occur in firefighters with underlying CHD. Improved fitness promotion, medical screening and medical management could prevent many of these premature deaths.

Full Article. PDF File.

Study 6 – A Study of Very Low Birth Weight Babies
Starting in the 1970s, advancements in neonatal intensive care allowed babies with very-low-birth-weight (less than 1500 grams, about 3.3 pounds) to survive and be free of serious handicaps. It was observed that these babies had difficulties in schools and in adulthood. A study followed 242 very-low-birth-weight babies born between 1977 and 1979, along with a control group of 233 babies from the same population born with normal birth weights. The study followed the participants from birth to young adulthood. The goal of the study was to assess the level of education, cognitive and academic achievement, and rates of chronic illness and risk-taking behavior at 20 years of age.

Results of the study:

  • Fewer very-low-birth-weight young adults than normal-birth-weight young adults had graduated from high school.
  • Very-low-birth-weight men, but not women, were significantly less likely than normal-birth-weight controls to be enrolled in postsecondary study.
  • Very-low-birth-weight participants had a lower mean IQ and lower academic achievement scores.
  • Very-low-birth-weight participants had higher rates of neurosensory impairments and subnormal heights.
  • The Very-low-birth-weight group reported less alcohol and drug use and had lower rates of pregnancy than normal-birth-weight controls.

Conclusion: Educational disadvantage associated with very low birth weight persists into early adulthood.

Abstract. PDF File.

Study 7 – Prevalence of Diabetes among Men and Women in China
This is a national study conducted in China from June 2007 through May 2008
to estimate the prevalence of diabetes among Chinese adults. A nationally representative sample of 46,239 adults, 20 years of age or older, from 14 provinces and municipalities in China participated in the study.

After an overnight fast, participants underwent an oral glucose-tolerance test (OGTT) to identify undiagnosed diabetes and prediabetes (i.e., impaired fasting glucose or impaired glucose tolerance). Previously diagnosed diabetes was determined on the basis of self-report.

The study found that about one in four Chinese adults are either diabetic or prediabetic (prevalence of diabetes and prediabetes are 9.7% and 15.5%, respectively). This translates to 92.4 million adults with diabetes and 148.2 million adults with prediabetes in China.

With respect to gender, the prevalence of diabetes is 10.6% for men and 8.8% for women and 15.5% and the prevalence for prediabetes is 16.1% for men and 14.9% for women.

The prevalence of diabetes increased with increasing age, from 3.2% (age group 20 to 39), 11.5% (age group 40 to 59) to 20.4% (age group 60 and over). The prevalence of diabetes also increased with increasing weight, from 4.5% (body-mass index of less than 18.5), 7.6% (BMI 18.5 to 24.9), 12.8% (BMI 25 to 29.9) to 18.5% (BMI 30 and over).

The prevalence of diabetes was higher among urban residents than among rural residents (11.4% vs. 8.2%).

The study concluded that diabetes has become a major public health problem in
China and that strategies aimed at the prevention and treatment of diabetes are

Article. PDF File.

Study 8 – Actos is found to be effective in preventing diabetes
People at high risk of developing diabetes may be able to prevent the disease by taking the drug pioglitazone according to a new study published in The New England Journal of Medicine (in March 2011). Pioglitazone, sold under the brand name Actos, is an anti-diabetic drug used along with a proper diet and exercise program to control high blood sugar in patients with type 2 diabetes.

In this study, a team of researchers at the University of Texas Health Science Center in San Antonio followed patients who were pre-diabetic (patients with elevated blood sugar levels but had not yet developed diabetes). A total of 602 patients were randomly assigned to receive pioglitazone or placebo. The median follow-up period was 2.4 years. Fasting glucose was measured quarterly and oral glucose tolerance tests were performed annually. Diagnosis of diabetes was confirmed on the basis of the results of repeat testing.

The annual incidence rate of diabetes was 7.6% for the placebo group and 2.1% for those taking pioglitazone, representing a 72% reduction in risk.

NY Times Article.
Times Article.

This entry was posted in Observational Studies, Randomized Experiments, Statistical studies, Statistics and tagged , , , , , , , . Bookmark the permalink.

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