Under what conditions may it be acceptable to abbreviate a CSR?
An abbreviation of a clinical study report is accepted when; the policy of the authority accepts abbreviation, in cases where some data was lost and where the study involved does not seek to clarify a phenomenon.
Where in the CSR should a sample of the ICF be placed?
At the beginning of the study report.
What information should be included in the “Investigational Plan”?
This part contains information on how the study will be carried out. This information include what population is to be studied and the criteria of choosing a sample is specified. This section also specifies the treatments under study and the way they are given. Diagrams are used to make the study be easily understood.
What is the purpose of “Disposition of Patients” diagram?
This diagram shows the behavior of the population under study. It shows; the number of people who get treated at every stage, those who did not pass through every stage and reasons for being left out are stated. The number of people who are screened and those excluded from screening is also shown in the disposition diagram.
Give 3 examples of “experimental hypotheses” as defined in Wiki.
An experimental hypothesis is a statement that a statician states. The statician then aims at proving whether this statement is true. It shows the dependent variable which is a cause and the independent variable which is similar to an effect.
Why is “random sampling” critically important in statistics?
Random sampling is a method that gives equal probability of being chosen for all items in a population. Random sampling is useful because it eliminates bias. Bias is a situation where some items have a higher probability of being chosen than others.
Do the descriptions of processes of “data cleaning” in Wiki match the process of data cleaning in clinical research? Explain.
Data cleaning is the process of eliminating variables that do not follow a pattern formed by other variables. Data cleaning in wiki is similar to that in clinical research. In clinical research, the doctor uses his own judgement to eliminate observations of certain patients. Elimination of some patients results is known as data cleaning. This is because patients who are eliminated do not follow a certain criteria.
What do the mean, mode, and median tell us?
Mean of a data shows the expected value. The mode shows the value that is most frequent, while the median shows the value that is at the middle of all others.
What does variance and standard deviation tell us about a population?
The standard deviation of a data shows the spread of the data around the meanwhile the variance is the square of the spread of data around its mean.
Why is a basic understanding of “probability” vital to the clinical researcher?
Knowledge of probability is important to a clinical researcher as it helps them in understanding of various probability distributions such as the normal distribution which is common. Probability helps a researcher to know the chances of a certain phenomenon occurring as well as the chances for non occurrence.
In the section “Testing Statistical Hypotheses”, how do we determine if two populations are similar or statistically different?
Testing statistical significance of two populations involves testing for the difference between the means of these populations. The two populations must have a normal distribution and their standard deviations must be known in advance.the null hypothesis states that the means of the populations is equal while the alternative hypothesis states that the means are different. A level of significance at which testing is done is chosen. If the null hypothesis is accepted, it means the two populations are similar. Rejection of the null hypothesis means the populations differ.
What is the purpose of “significance testing”?
Significance testing is done to tell whether a certain hypothesis is true or false.
Statistical Slide Presentation (revisited)
Can “observational data gathering” (like number of men and women dying from lung cancer OR distribution of types of brain tumors among humans) yield important information? Explain.
Yes, it helps identify details that the respondent may not tell the researcher, but which are important to the study.
What are the two ages groups associated with significantly higher numbers of auto accidents involving deaths?
19-20 and 21-24 years
Which 3 variables in the t-test equation collectively determine “significance”?
Mean, standard deviation and population size
Can you manipulate clinical study design to increase the likelihood of detecting a significant difference between 2 populations? Explain.
Yes, this can be achieved through modifying the variables that affect the significant difference; for example, increasing the population size.
The Typical FDA Drug Approval Process
How can the sponsor remove a “clinical hold” placed by the FDA on a potential clinical study presented in the IND?
Do you need to complete long-term animal safety in order to start a phase 2 trial? Explain.
No, you cant start phase 2 during this period using early access.
FDA Accelerated Approval (revisited)
What is the general basis for determining usual or accelerated approvals?
Usual approval is determined if diagnosis with a certain drug provides longer and better life to patients. Accelerated approval on the other hand is determined on grounds that are weaker than those of determining usual approval.
US Code of Federal Regulations (CFR) - The Animal Efficacy Rule
According to the letter of the law, when does this rule “apply”?
The animal efficacy rule applies to situations where it is not possible to conduct a study to test the drug involved.
The rule was in discussion in 1999 and approved in 2002. Why do you think it was approved in 2002 (a reasonably fast process)?
This rule was approved in 2002 because the drugs were found to make the worst conditions be better. The drugs were found to lengthen the life of a person. The rule was also approved because testing of the drugs was found to be almost impossible. This is because testing the drug would result to worsening of the health of a person.
When does this rule Not apply?
The rule is not applicable where a drug can be tested using set standards. Instead of using this rule, a drug is approved if it meets the set standards.
Federal CFR - Animal Rule Slide Set
Why is this rule called the “Efficacy” rule?
If you believe that your drug requires approval via the Animal Efficacy rule, what should your IND (data packet) contain?
The Animal Efficacy Rule - Listing of Approvals
In general, what characteristics do these approvals share?
Findings from the FDA are analyzed before making the final decision.
The purpose, benefits and risks of a drug are considered.
The data from pre-trial and clinical studies is analyzed.
MOST RECENT Drug Approved via the "Animal Rule" - Raxibacumab
What is the indication for this new drug?
For the treatment of anthrax in patients when the condition is caused by Bacillus Anthracis.
How is this drug administered?
The drug is administered intravenously
What is the only warning regarding this drug?
It may possess infusion reactions
In the major population (N = 283) what were the 4 AEs reported?
The Development of a MoAB for Treatment of Rare Disease - FDA Type 2 Meeting Re: Animal Rule Approval Path
What was the “Osaka outbreak”?
It was an outbreak of the norovirus in a hospital in Osaka
Why did the company predict “no return in investment”?
The cost of flushing out the infected milk, conducting studies to identify the cause of the infection and funding PR campaigns resulted in no profit margins for the company.
What were 4 of the major reasons why this trial might be difficult or impossible to conduct?
The risks involved were high
The cost of funding the research was high
It involved healthy patients yet the drug was meant for infected people.
The adverse reactions associated discouraged other participants from volunteering in the study.
Did the FDA agree that the protocol design was adequate?
No, they did not.
What were some of the reasons for the high incidence of STEC infection in this foreign country?
There was increased bacterial production in a dairy plant at Osaka during a power outage. The STEC was caused when dairy products from the firm were sold to consumers.
Of the 4 potential trials suggested by the sponsor, how long would it take to complete the longest trial,,,,,the shortest trial? Why the difference?
Carcinogenicity, fertility studies, genotoxicity, and animal studies
What were the two most useful animal models for this infection? Were the results of treatment impressive / repeatable?
Rabbit and monkey models.
The results were impressive.
STEC Infection in Washington State
Briefly describe the parameters of this infection:
How many cases reported?
How many hospitalized?
How many cases of HUS?
How many deaths?
What was determined to be the cause of this outbreak?
E-Coli resulting from unhygienic meat cooking and processing
What was the most recent STEC outbreak in the US?
It was the Shiga Toxin outbreak in June 2012
Did it involve beef? Describe.
The CDC was not able to identify the source of the E-Coli infection
What parts of the US were involved?
Florida, California, Georgia, Alabama, Maryland, Kentucky, Virginia, Louisiana and Tennessee
A Mini Seminar in Drug Advertising
What is the role of the OPDP?
It ensures public health by making sure that prescription drugs meet the health and medical requirements set in place.
Why is DTC advertising a “relatively new area of prescription drug promotion”?
This is because pharmaceutical companies used to target health care organizations and middle-men but are now engaging customers directly. This form of advertising is also new because it begun only 15 years ago.
A “product claim ad” must contain 4 key components: _____?
Condition it treats
What is a “boxed warning”? Is it important?
It is a warning on the packaging of a drug indicating that the medicine poses significant risk for the consumer. This warning is essential since it is a national standard set by FDA, which helps protect consumers.
What is “fair balance”?
Presentation of an accurate analysis of the risks associated with a drug and its advantages.
What is the “prescribing information”?
It is a piece of literature inserted into a drug’s packaging that indicates how a drug should be used, the side-effects and its purpose.
Briefly, what are the 4 problems with the “Incorrect Product Claim” ad?
- It did not state all the risks of the product.
- It did not indicate that the product could only be sold and distributed by licenced practitioners.
- It did not precisely state the uses of the product.
- The advertising was misleading
TV and Radio-generated Warning Letters
What were the FDA’s two major concerns regarding the “Quadramet” advertisement?
- Failing to disclose essential information about the risks of the drug.
- Overstating the effectiveness of the drug
Why is conducting and pursuing the development of a potential cancer drug different, relative to most other therapeutric areas?
Because developing a cancer drug requires more studies that increases the costs of research and production.