Pod 2 a ( research- evidence)

Question 1

0st phase of clinical research for drug/device approval

Answer 1

0: exploratory. first in human trials conducted in accordance to FDA. Often uses microdosing. Less ppl are involved. very early process.

Question 2

1st phase of clinical research for drug/device approval

Answer 2

20-100 ppl involved. healthy vounteers. assess safety (pharmacovigilance), tolerabolity, pharmacokinetics and pharmacokdynamics of the drug. uses safety est from phase 0. uses low doses!

Question 3

2nd phase of clinical research for drug/device approval

Answer 3

20-300ppl. design it assess how well the drug works. continuation of safety from phase 1. often the phase the drug fails in because it doesnt do as planned or is toxic.
e.g Jesse Gelsinger an the ornithine transcarbamylase deficiency. ( liver transplant and has a low protein diet and died– build up of ammonium in the diet).

Question 4

3rd phase of clinical research for drug/device approval

Answer 4

randomized controlled multicenter trials on large patient groups. (300-3000 or more). aimed at being the definitive assesment of how effective the drug is in comparison with the current “ golden standard” treatment.
this is the phase when ppl invest their money “ prospects look good”

Question 5

4th phase of clinical research for drug/device approval

Answer 5

Post maketing surveillance trial. safety surveillance (pharmacovigilance) and ongoing technical support of a drug after it receives permission to be sold. Continued technical support is required now, esp with antibiotics. Need to monitor the resistance of the drug- then FDA can change label. This phase is a large expense to pharm companies. ( they could come to me and ask how my patients fair with it.

Question 6

5th phase of clinical research for drug/device approval

Answer 6

growing term- “translational research” to refer to comparative effectiveness research and community based research. it is used to signify the integration of new clinical treatment into widespread public health practice. (integration of treatment and correlation with public health) determines if there are positive effects overall or not.

Question 7

Difference between observational and treatment research studies?

Answer 7

OBSERVATIONAL: looks directly at ppl groups and direct issue.
collect data on something already there
include cohort, cross sectional, and case control studies.
TREATMENT randomness important in studying a group.
test something unknown.
reduce bias
hypothesis driven!
this is the “gold standard” in clinical research
randomized control trial

Question 8

main features of major clinical research study designs?

Answer 8

not sure

1. having a hypothesis: proposed explanation for a phenomenon… must be something testable.

Question 9

Significance of study design planning and following accepted research guidelines?

Answer 9

not sure
is it ethical?
hypothesis driven?

Question 10

Evidence based practice?

Answer 10

EBP: integration of the best evidence coupled with clinical expertise. enables practitioners to address healthcare questions with an evaluative approach. Allows practitioner to assess current and past research, clinical guidelines and other information in order to identify relevant literature while differentiating findings between high vs low quality findings.

Question 11

Why do we do research?

Answer 11

Evidence based medicine. understand the pathways of our health. legal obligation, intellectual curiosity, academic credence.

Question 12

What is research?

Answer 12

“systematic investigation” is an activity that involved a prospective plan that incorporates data collection, either quantitative or qualitative, and data analysis to answer a question.
e.g focus groups, medical chart review, analysis of specimens, surveys, etc.

Question 13

Features of research that are meant to contribute to generalized knowledge….

Answer 13

need to draw conclusions, inform policy, produce generalized findings beyond yourself/internal program, you have the responsibility to share what you have learned. Whether published or not, individuals involved should be protected.

Question 14

Case Studies are considered…?

Answer 14

are important however not deemed by the Federal Review Body as “research.” this is because it is not generalized information and rather based on one specific individual. At DMU we review case studies, they go through an institutional review before a publication accepting them.

Question 15

What are the levels of evidence? Lowest to highest value…

Answer 15

1. expert opinion “ experts say that…” ( lowest confidence)
2. cross sectional studies and case studies
3. uncontrolled longitudinal studies “there are signs that”
4. controlled longitudinal studies “ it is likely that”
5. randomized control studies “ it is shown that” ( high confidence)… also includes meta-analysis which reviews randomized control trials.

Question 16

research ethics in general

Answer 16

essential to conform to accepted standards of social or professional behavior. adhering to ethical and moral principles is learned, not always assumed. If you mess up… you will not be able to return to your career.

Question 17

Research Ethics Guidelines:

Answer 17

honesty ( convey info accurately)
accuracy ( report info precisely)
objectivity ( avoid bias)
and efficiency ( avoid waste)

Question 18

What are the types of Observational Studies?

Answer 18

1. Cohort Study ( prospective cohort and retrospective cohort)
2. Case control study
3. Cross sectional study

Question 19

What is a cohort study?

Answer 19

aka Panel study. form of a longitudinal study used in medicine. analysis of risk factors. follows group of ppl who DO NOT have the disease. uses correlations to determine the absolute risk of subject contraction. These studies use life histories of segments of populations.
types: prospective/retrospective cohorts.

Question 20

Definition of Case control study?

Answer 20

type of study design in epidemiology. used to identify factors that may contribute to a medical condition… this is done by comparing subjects who HAVE the condition to those who DO NOT- but are otherwise similar. These are inexpensive, frequently used, can be carried out by small teams, or individuals in single research facilities (whereas other studies are not able to be carried out by these ppl)

Question 21

What is a cross sectional study? (hint- this is a type of observational study)

Answer 21

aka cross sectional analysis. observations of a population or a representative subset. Goal to provide data on the entire population under study. ( Different from control studies who only provide info on population of interest- a minority, group affected by a certain disease).

Question 22

What are some details about cross sectional studies?

Answer 22

data collected at a defined time. Often used to assess the prevalence of acute or chronic conditions, or may answer questions about the causes of disease or results of medical intervention. Also referred to as “consensuses”. expensive research that is not intended for rare disease research. ( there would not be enough ppl to participate)

Question 23

What are some characteristics of treatment studies?

Answer 23

randomized control trial ( RTC)
form of a clinical trial , that is most likely used in testing the safety of drugs (adverse reactions/effects). Also study the efficacy or effectiveness of healthcare services ( medicine or nursing), also health technologies ( pharm/device) companies
e.g. double, single, or non blind trials.

Question 24

What are the measures of randomness involved with Random Control Trials>

Answer 24

after study subjects are selected, the treatment they will receive is randomized. we want to decrease chance of bias.

Question 25

characteristics of double blind randomized trial?

Answer 25

both the investigator and the study subject have no idea what the treatment is.goal= to produce very objective results- no bias.

Question 26

Single Blind?

Answer 26

experimental procedure…. experimenter knows, but the study subject does not. e.g. surgery research would have to be a single blind ( surgeon must know what’s happening).

Question 27

Non blind?

Answer 27

neither the experimenter nor the study subject is blind… this might also be a surgery scenario.

Question 28

What is a non randomized trial? ( Quazi experiment)

Answer 28

takes measurements of a population before and after manipulation.
“interrupted time series design”
good research, however lacks a control… be careful about your inferences!!!!

Question 29

Case control study example….

Answer 29

40 study subjects. ( 20 with plantar fascitis and 20 controls). Study looked to see differences in ROM of 1st digit and peak resistance when testing flexor strength
make sure each case is matched with a control, this is the key to success.
we need to have a baseline idea. It can be a challenge to pair up controls.
( those with PF had weaker flexors than controls)

Question 30

this experiment is looking at bone fractures in a cross section of 9/10th grade girls… what type of study is this?

Answer 30

Cross sectional…

Question 31

Value of statistics?

Answer 31

need to be considered prior to testing, you can not manipulate data enough if the results are intrinsically flawed.
cofounders: taken out or not… ppl that throw off ranges.
size of participate pool?
how will we analyze data?

Question 32

Literature biases?

Answer 32

who published it?
who funded it?
who performed it? ( university, non profit, appointed scientists bases on training and accomplishments)
how does info compare to past studies?
did the study have controls?!!! you need this!

Question 33

Definition of Evidence Based Practice:

Answer 33

examination of the evidence from clinical research to justify the diagnosis, prognosis, and the treatment of patients. The type of treatment rendered is a combination of evidence in literature and the personal experience of the health care professional! Important to have the combo!

Question 34

How do you perform a literature search for articles most appropriate and related to EBP?

Answer 34

1. go to lib.dmu.edu
   select journal and evidence based research
2. frame your question well
3. try to find a meta-analysis, systematic review or a RCT ( randomized control trial). make sure they used a control group!

OR use PubMed and Google

Question 35

Steps learned in analyzing medical literature?

Answer 35

1. proper search techniques
2. determine level of evidence the literature provides
3. validity of study…

Question 36

What were the concepts behind validity with treatment control studies and systematic reviews?

Answer 36

Within treatment control studies: need to make sure that the controls are similar to the patients actually receiving the treatment. Make sure we have good follow up of the patients ( >80%), Randomization is also important for RCT- dont want to get false positives. Size of trial is important- min of 100, 400 is best! drop outs? how best to handle ( if thrown out- often falsely increases validity)

Question 37

Can I just listen to experts?

Answer 37

nah… that is level 5… very poor. This was valued in old school approach.

Question 38

can observations be biased?

Answer 38

Yes! that is why we use systematic scientific approaches to analyze the observations! ( New School train of thought)

Question 39

List the types of research done that present evidence level from the highest to lowest categories?

Answer 39

1a. . meta-analysis (BEST)
1b. systematic review
1c. randomized controlled trial
2a. cohort studies or lesser quality randomized control tests
3. case-control studies ( this is where most of our evidence comes from!)
4. case series/case reports
5a. animal research/laboratory studies/cadaver studies ( these are low evidence, but not worthless).
5b. EXPERT OPINION

Question 40

what are case series research?

Answer 40

A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment.

Question 41

what is a cohort study?

Answer 41

The analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of cohort study is observation of large numbers over a long period (commonly years) with comparison of incidence rates in groups that differ in exposure levels.

Question 42

what is a confidence interval?

Answer 42

Confidence interval (CI): The range around a study’s result within which we would expect the true value to lie. CIs account for the sampling error between the study population and the wider population the study is supposed to represent.

Question 43

what is an observational study?

Answer 43

Observational study: A family of studies in which investigators compare people who take an intervention with those who do not. The investigators neither allocate patients to receive the intervention not administer the intervention. Instead, they compare records of patients who had taken an intervention and been treated in routine practice with similar patients who had not taken the intervention. The most common observational designs are case-studies, case-series, case-control studies, cohort studies, and historically controlled studies. (Howick)

Question 44

describe what a p value tells me?

Answer 44

p value: The probability that a particular result would have happened by chance.

Question 45

what is a systematic review?

Answer 45

Systematic review: The application of strategies that limit bias in the assembly, critical appraisal, and synthesis of all relevant studies on a specific topic. Systematic reviews focus on peer-reviewed publications about a specific health problem and use rigorous, standardized methods for selecting and assessing articles. A systematic review may or may not include a meta-analysis, which is a quantitative summary of the results.

Question 46

what is the validity of study referring to?

Answer 46

Validity: The extent to which a variable or intervention measures what it is supposed to measure or accomplishes what it is supposed to accomplish. The internal validity of a study refers to the integrity of the experimental design. The external validity of a study refers to the appropriateness by which its results can be applied to non-study patients or populations.

Question 47

What are therapeutic studies and how do they related to the level 1 and 2 of evidence meter?

Answer 47

Therapeutic studies: investigate results of treatment.
level 1. high quality randomized controlled trial, no significant difference, narrow confidence intervals, study results are homogenous
level 2: lesser quality, less than 80% follow up, no blinding,

Question 48

what are prognostic studies and how are they related to level 1 and2 evidence?

Answer 48

prognostic levels: investigating the effect of a patient characteristic on the outcome of the disease.

1. high quality, all patients enrolled at same time, greater than 80% follow up.
2. lesser quality, patients enrolled at different times, may be a retrospective study with untreated controls.

Question 49

Are systematic or meta-analytic reviews always level 1?

Answer 49

NO! depends on the level of the review papers you look at. Only as strong as your weakest link. If you analyzed level 2 papers.. then you have LEVEL 2 evidence. not unusual to see at level 2 or 3.

Question 50

what is the rating of evidence?

Answer 50

level A: 2 or more RCT in humans, meta-analysis of RCT,
level B: 1 or more supporting controlled trials in an animal model
Level C: 1 supporting controlled trial , at least 2 support case series that were descriptive studies in humans, or expert opinion.

Question 51

Three steps to organize EBM process?

Answer 51

1. ask- frame the research question
2. acquire the evidence
3. appraise and apply the evidence

Question 52

what does PICOT stand for and relate to?

Answer 52

a way to craft your question in a way that is focused and clinically answerable.
ppl you are “ population you are interested in?”
intervention “ what is the treatment or therapy?”
comparison “ what are you measuring against?”
outcomes “ what do you want to measure or prove?”
type of study. “ diagnosis, prognosis?”

Question 53

More about prognosis

Answer 53

refers to possible outcomes of a disease and the frequency at which they are expected to occur. prognostic factors can predict any outcome ( not the same as risk factors), whether good or bad. factors do not necessarily cause outcomes, just be associated with them long enough to predict their development. factors are patient characteristics that hep predict whether the patient will recover or relapse.

Question 54

surgical studies are done through what method?

Answer 54

prognostic or case control studies…. this isnt the best level of evidence, but we can work with it.
(… a Randomized control study for surgery patients would NOT be ethical- cannot open all, but only have half receive the actual procedure) lol.

Question 55

what is the difference between prognosis factors vs risk factors?

Answer 55

PF: patient characteristics predicting whether the patient will recover or relapse. ( patient with breast cancer that has positive estrogen markers- decreased chance of survival)
RF: patient characteristics associated with development of a disease or condition ( older woman more are risk to develop breast cancer)

Question 56

Case control studies -retrospective…

Answer 56

Retrospective: looking back on data. requires memory and trust that data was collected correctly, this also contains more bias. limits strength… and thus why level 3.

Question 57

case control studies that are prognostic?

Answer 57

prognostic: going to collect data ( good)… however was there a representative patient sample ( diversity) at a well defined point of the disease course( all at same point of disease course)? was the follow up sufficiently long and complete? were objective outcome critera applied in “blind fashion”? ( blind investigators from patient characteristics and that of their prognosis factors in order to elimiate bias.)

Question 58

how valid is the meta- analysis?

Answer 58

did the review address a clearly focused question?
were criteria used to select articles?
were studies of high quality?
was the search detailed and exhaustive?
were authors contacted in regards to questions?