Primary Resources Primary Resources

practice of medicine and pharmacy is practice of medicine and pharmacy is dynamicdynamic, and , and drug facts acquired during formal education cannot drug facts acquired during formal education cannot sustain a health care provider in future practice.sustain a health care provider in future practice.

Changes include: Changes include: new medications new medications dosage formulationsdosage formulations uses approved by the Food and Drug Administration (FDA)uses approved by the Food and Drug Administration (FDA) revised drug safety information (i.e., adverse drug effects and drug revised drug safety information (i.e., adverse drug effects and drug

interactions) interactions) and updated disease state therapeutic guidelinesand updated disease state therapeutic guidelines

Therefore, skills, such as drug literature Therefore, skills, such as drug literature evaluation, are necessary to prepare the health evaluation, are necessary to prepare the health care provider for practice.care provider for practice.

Furthermore, pharmacists must employ Furthermore, pharmacists must employ

methods to keep current with these advances methods to keep current with these advances in order to remain competent, trustworthy in order to remain competent, trustworthy health care professionals. health care professionals.

types of publications (examples) types of publications (examples)

controlled trials controlled trials cohort studiescohort studies case reportscase reports

Advantages of the use of primary Advantages of the use of primary literature literature

access to detailed information about a topic access to detailed information about a topic

ability to personally assess the utility and ability to personally assess the utility and validity of study results validity of study results

primary literature tends to be more recent than primary literature tends to be more recent than tertiary or secondary literature tertiary or secondary literature

disadvantages of using primary disadvantages of using primary literature alone literature alone

misleading conclusions based on only one trial misleading conclusions based on only one trial without the context of other researches without the context of other researches

the need to have good skills in medial the need to have good skills in medial literature evaluation literature evaluation

the time needed to evaluate the large volume the time needed to evaluate the large volume of literature available of literature available

peer-review processpeer-review process peer-reviewed articles are evaluated by someone other than the editorial peer-reviewed articles are evaluated by someone other than the editorial

staff (i.e., evaluation by one's peers)., staff (i.e., evaluation by one's peers).,

Most journals incorporate the peer-review process in selecting articles for Most journals incorporate the peer-review process in selecting articles for publicationpublication

manuscripts submitted to the journal for publication consideration are manuscripts submitted to the journal for publication consideration are screened by the editor; those deemed as potential publications are sent to screened by the editor; those deemed as potential publications are sent to individuals with expertise in the appropriate areaindividuals with expertise in the appropriate area

These individuals read the manuscript and comment on the strengths and These individuals read the manuscript and comment on the strengths and limitations, plus offer a recommendation to the journal editor regarding limitations, plus offer a recommendation to the journal editor regarding accepting or rejecting the manuscript for publicationaccepting or rejecting the manuscript for publication

The peer-reviewers' comments are sent to the authors for the manuscript to The peer-reviewers' comments are sent to the authors for the manuscript to be revised and, if necessary, resubmitted for publication considerationbe revised and, if necessary, resubmitted for publication consideration

Commonly Encountered Biomedical Commonly Encountered Biomedical Literature Literature

controlled, clinical trials (interventional trial ): controlled, clinical trials (interventional trial ): serves as the foundation for clinical practice by providing the serves as the foundation for clinical practice by providing the

documentation for using therapy documentation for using therapy In general, a controlled clinical trial consists of an investigational In general, a controlled clinical trial consists of an investigational

(intervention) group being directly compared to a control group (e.g., (intervention) group being directly compared to a control group (e.g., standard therapy, placebo)standard therapy, placebo)

The The interventionintervention under investigation may be under investigation may be a new medication, a new medication, different medication dosing regimen, different medication dosing regimen, diet, diet, surgery, surgery, behavioral process, behavioral process, exercise program, exercise program, diagnostic procedure, diagnostic procedure, or something else. or something else.

Format and Content of Controlled Format and Content of Controlled Clinical Trials Clinical Trials

AbstractAbstract: Brief overview of the research : Brief overview of the research project project

IntroductionIntroduction: Research background and : Research background and Clinical trial objectiveClinical trial objective

MethodologyMethodology: : Study design Study design Patient inclusion and exclusion criteria Patient inclusion and exclusion criteria Intervention and control groups Intervention and control groups Randomization Randomization Blinding Blinding Endpoints Endpoints Follow-up procedure Follow-up procedure Sample size calculations/power analysis Sample size calculations/power analysis Statistical analysis Statistical analysis

ResultsResults Subject characteristics Subject characteristics Subject dropouts/compliance Subject dropouts/compliance Endpoints quantified Endpoints quantified Safety assessments Safety assessments

DiscussionDiscussion Result interpretations Result interpretations Other study results compared Other study results compared Limitations Limitations

AcknowledgmentsAcknowledgments Other contributors Other contributors Funding source Funding source Peer-review dates/manuscript acceptance date (not all trials) Peer-review dates/manuscript acceptance date (not all trials)

References/BibliographyReferences/Bibliography Citations for information included from other resources (e.g., Citations for information included from other resources (e.g.,

trials and reports) trials and reports)

AbstractAbstract a concise overview of the study or a synopsis of the a concise overview of the study or a synopsis of the

major principles of the articlemajor principles of the article

Abstracts include information addressing the article Abstracts include information addressing the article objective, methods, results, and conclusionsobjective, methods, results, and conclusions

A primary use of abstracts is for readers to obtain an A primary use of abstracts is for readers to obtain an immediate overview of the article to determine if the immediate overview of the article to determine if the entire article should be readentire article should be read

Another use is publishing the abstract in secondary Another use is publishing the abstract in secondary resources (e.g., PubMed® and International resources (e.g., PubMed® and International Pharmaceutical Abstracts [IPA]) for individuals Pharmaceutical Abstracts [IPA]) for individuals conducting literature searches.conducting literature searches.

IntroductionIntroduction discussing the study rationale and study purposediscussing the study rationale and study purpose

readers are first briefly educated on the issues that were the readers are first briefly educated on the issues that were the basis of conducting the studybasis of conducting the study

The study investigators may state that the reason the research The study investigators may state that the reason the research was conducted is due to the lack of data to answer a question was conducted is due to the lack of data to answer a question or available data are conflicting regarding an issueor available data are conflicting regarding an issue

The investigators should explain how the clinical trial will The investigators should explain how the clinical trial will overcome the shortcomings of the prior research, if applicableovercome the shortcomings of the prior research, if applicable

The study objective is often stated within the last paragraph, if The study objective is often stated within the last paragraph, if not the last sentence, of this sectionnot the last sentence, of this section

A research hypothesis (also known as the alternative A research hypothesis (also known as the alternative hypothesis) is stated as "a difference is present hypothesis) is stated as "a difference is present between the therapy under investigation and the between the therapy under investigation and the control"control"

null hypothesis is stated as "no difference between null hypothesis is stated as "no difference between these two groups"these two groups"

After the study is completed, the researchers analyze After the study is completed, the researchers analyze the data and then the research hypothesis is either the data and then the research hypothesis is either accepted (which also includes rejecting H0) or accepted (which also includes rejecting H0) or rejected (which then means H0 is accepted). rejected (which then means H0 is accepted).

Readers should recognize that not all clinical trials Readers should recognize that not all clinical trials will include the specific research and null hypotheses will include the specific research and null hypotheses in the introduction sectionin the introduction section

An example (the Women's Health An example (the Women's Health Initiative (WHI) trial) Initiative (WHI) trial)

assessed the risks and benefits of the assessed the risks and benefits of the estrogen/progestin combination in healthy estrogen/progestin combination in healthy postmenopausal women postmenopausal women

The WHI trial compared conjugated equine estrogen The WHI trial compared conjugated equine estrogen plus medroxyprogesterone (CEE/MPE), with placebo. plus medroxyprogesterone (CEE/MPE), with placebo.

The investigators expressed in the introduction The investigators expressed in the introduction section that the rationale for conducting this clinical section that the rationale for conducting this clinical trial was the lack of human controlled clinical trials trial was the lack of human controlled clinical trials evaluating this product specifically for evaluating this product specifically for cardioprotective outcomes cardioprotective outcomes

Prior evaluations of this medication were Prior evaluations of this medication were predominately observational in design (i.e., not predominately observational in design (i.e., not clinical trials) and reported reductions in clinical trials) and reported reductions in adverse events:adverse events:

coronary heart disease [CHD] coronary heart disease [CHD] and hip fractureand hip fracture changes in clinical parameters (i.e., decreased lipid levels and changes in clinical parameters (i.e., decreased lipid levels and

increase bone mineral density) increase bone mineral density)

The actual WHI trial study objective was The actual WHI trial study objective was stated as stated as ". . . to directly address whether ". . . to directly address whether estrogen plus progestin has a favorable or estrogen plus progestin has a favorable or unfavorable effect on CHD incidence and unfavorable effect on CHD incidence and on overall risk and benefits in on overall risk and benefits in predominantly healthy women."predominantly healthy women."

The research hypothesis of the WHI trial is The research hypothesis of the WHI trial is "there is a difference in the incidence of CHD "there is a difference in the incidence of CHD between CEE/MPE and placebo" between CEE/MPE and placebo"

while H0 is "there is no difference in the while H0 is "there is no difference in the incidence of CHD between CEE/MPE and incidence of CHD between CEE/MPE and placebo." placebo."

MethodsMethods Study DesignStudy Design

A simple description of a controlled clinical trial is A simple description of a controlled clinical trial is that it prospectively measures a difference in effect that it prospectively measures a difference in effect between two therapiesbetween two therapies

The groups are similar and treated identically with The groups are similar and treated identically with the exception of the therapies under studythe exception of the therapies under study

The subjects in the study are assigned to one of the The subjects in the study are assigned to one of the groups and monitored.,,, This study type, called groups and monitored.,,, This study type, called parallel design, is the primary study design parallel design, is the primary study design encountered in the literature. encountered in the literature.

Patient Inclusion/Exclusion CriteriaPatient Inclusion/Exclusion Criteria

The inclusion criteria list subject demographics that The inclusion criteria list subject demographics that must be present to be enrolled into the trial, must be present to be enrolled into the trial,

exclusion criteria are characteristics that prevent exclusion criteria are characteristics that prevent enrollment into the trial or necessitate withdrawal from enrollment into the trial or necessitate withdrawal from the studythe study

Generally the inclusion criteria attempts to include Generally the inclusion criteria attempts to include subjects that are homogeneous and are similar to the subjects that are homogeneous and are similar to the common type of patients in practicecommon type of patients in practice

Intervention and Intervention and Control Control GroupsGroups Once the subjects to be enrolled in the clinical trial Once the subjects to be enrolled in the clinical trial

have been selected, these persons will be assigned to have been selected, these persons will be assigned to either the intervention or control groupeither the intervention or control group

The intervention group consists of the new therapy The intervention group consists of the new therapy under investigation (e.g., medication, procedure). under investigation (e.g., medication, procedure).

The intervention is compared to a control so that the The intervention is compared to a control so that the fundamental principle of a controlled clinical trial can fundamental principle of a controlled clinical trial can be accomplished, measuring cause and effect.be accomplished, measuring cause and effect.

The control group can consist of no therapy (e.g., The control group can consist of no therapy (e.g., placebo), or another therapy (e.g., drug and exercise)placebo), or another therapy (e.g., drug and exercise)

Both the intervention and control groups are to be the Both the intervention and control groups are to be the same in all respects other than the treatment receivedsame in all respects other than the treatment received

Afterward, the investigators will measure and Afterward, the investigators will measure and quantify a difference in effect between the group quantify a difference in effect between the group assigned to the intervention with those in the control assigned to the intervention with those in the control group. Thus, any identified differences in the group. Thus, any identified differences in the measured effect can be attributed to intervention measured effect can be attributed to intervention rather than other factors.,,rather than other factors.,,

BlindingBlinding Since clinical trials measure differences in effect Since clinical trials measure differences in effect

between groups, outside influences (i.e., biases) between groups, outside influences (i.e., biases) should be minimizedshould be minimized

This is especially important in studies measuring This is especially important in studies measuring subjective outcomes (e.g., pain, depression scores)subjective outcomes (e.g., pain, depression scores)

Blinding is a technique in which subjects and/or Blinding is a technique in which subjects and/or investigators are unaware of who is in the investigators are unaware of who is in the intervention or control groupintervention or control group

Blinding techniques are incorporated to reduce Blinding techniques are incorporated to reduce possible bias possible bias

Patients knowing that they are taking a Patients knowing that they are taking a placebo to reduce depression symptoms are placebo to reduce depression symptoms are very likely to report no change or worsening of very likely to report no change or worsening of the diseasethe disease

The results are biased since subjects The results are biased since subjects knowingly are taking a substance that does not knowingly are taking a substance that does not reduce symptomreduce symptom

No blinding (open-label): Investigators and subjects No blinding (open-label): Investigators and subjects are aware of the assignment of subjects to the are aware of the assignment of subjects to the intervention or control groupintervention or control group

Single blinding: Either investigators or subjects, but Single blinding: Either investigators or subjects, but not both, are aware of the assignment of subjects to not both, are aware of the assignment of subjects to the intervention or control group the intervention or control group

Double blinding: Both investigators and subjects are Double blinding: Both investigators and subjects are not aware of the assignment of subjects to the not aware of the assignment of subjects to the intervention or control groupintervention or control group

Randomization Randomization Randomization is a distinguishing study Randomization is a distinguishing study

attribute that separates controlled clinical trials attribute that separates controlled clinical trials from other study designs (e.g., case-control from other study designs (e.g., case-control and cohort). and cohort).

A basic definition of randomization is "all A basic definition of randomization is "all study subjects have an equal chance of being study subjects have an equal chance of being 'assigned' to either the intervention or control 'assigned' to either the intervention or control group." group."

Research has indicated that the results Research has indicated that the results obtained from randomized trials are more obtained from randomized trials are more dependable than nonrandomized trialsdependable than nonrandomized trials

Randomization minimizes bias by lowering Randomization minimizes bias by lowering the potential for an imbalance of risk factors or the potential for an imbalance of risk factors or prognostic variations between the intervention prognostic variations between the intervention and control groupsand control groups

EndpointsEndpoints

"what did the investigators measure to achieve "what did the investigators measure to achieve the study objective?the study objective?

For example, a trial evaluating the cholesterol For example, a trial evaluating the cholesterol lowering effect of a statin compared to placebo lowering effect of a statin compared to placebo selected a change in average LDL-C value, an selected a change in average LDL-C value, an appropriate measure, as the primary endpoint appropriate measure, as the primary endpoint to satisfy the study objectiveto satisfy the study objective

Sample SizeSample Size Sample size (denoted by the letter n) refers to the number of Sample size (denoted by the letter n) refers to the number of

subjects randomized into a study and is of considerable subjects randomized into a study and is of considerable importance to the validity of the study results.importance to the validity of the study results.

Financial and logistical limitations prevent all subjects with Financial and logistical limitations prevent all subjects with the specific inclusion criteria from being enrolled into the the specific inclusion criteria from being enrolled into the studystudy

For example, investigators want to evaluate a new drug to treat For example, investigators want to evaluate a new drug to treat hypertensionhypertension

It would be virtually impossible to enroll all people with It would be virtually impossible to enroll all people with hypertension into this clinical trialhypertension into this clinical trial

In response, investigators will draw a representative group (i.e., sample) of In response, investigators will draw a representative group (i.e., sample) of individuals from all those with hypertension (i.e., population)individuals from all those with hypertension (i.e., population)

inverse relationship exists between the sample size and the effect sizeinverse relationship exists between the sample size and the effect size

A large sample size is needed to detect a small difference in effect between A large sample size is needed to detect a small difference in effect between the intervention and control outcome while a smaller sample size is needed the intervention and control outcome while a smaller sample size is needed to detect large differences between the two groupsto detect large differences between the two groups

A large sample size is needed to detect differences in blood pressure A large sample size is needed to detect differences in blood pressure between two antihypertensive therapies (small difference in blood pressure between two antihypertensive therapies (small difference in blood pressure reductions) while a smaller sample size is needed to measure the difference reductions) while a smaller sample size is needed to measure the difference in relieving postoperative pain between morphine and placebo (large in relieving postoperative pain between morphine and placebo (large difference in pain relief). difference in pain relief).

Statistical Analysis Statistical Analysis The purpose of statistical analysis of the study data is The purpose of statistical analysis of the study data is

to collect sufficient evidence to reject the null to collect sufficient evidence to reject the null hypothesis (H0) in favor of accepting the research hypothesis (H0) in favor of accepting the research hypothesis (H1) hypothesis (H1)

Descriptive statistics describe the characteristics of Descriptive statistics describe the characteristics of the sample (e.g., average subject age, baseline the sample (e.g., average subject age, baseline endpoint values, number of subjects with another endpoint values, number of subjects with another disease present) and the results in some studies (e.g., disease present) and the results in some studies (e.g., XX% had an adverse effect) % had an adverse effect)

Inferential statistics are used to determine if a Inferential statistics are used to determine if a statistical difference is present between the statistical difference is present between the intervention and control groups. A intervention and control groups. A p valuep value is is calculated based on trial results and statistical tests calculated based on trial results and statistical tests

Other statistical terms encountered while Other statistical terms encountered while reading clinical trials are unpaired versus reading clinical trials are unpaired versus paired and one-tailed versus two-tailed paired and one-tailed versus two-tailed statistical analysis statistical analysis

Comparing results between groups is referred Comparing results between groups is referred to unpaired analysis, while within a group to unpaired analysis, while within a group comparison is a paired analysis comparison is a paired analysis

For example, measuring the mean change in For example, measuring the mean change in LDL-C from baseline to 12 weeks with LDL-C from baseline to 12 weeks with simvastatin would be a paired analysis simvastatin would be a paired analysis

Analyzing the mean difference in the LDL-C Analyzing the mean difference in the LDL-C reduction after 12 weeks between simvastatin reduction after 12 weeks between simvastatin and atorvastatin would be considered an and atorvastatin would be considered an unpaired test unpaired test

Two-tailed (also known as two-sided) statistical tests Two-tailed (also known as two-sided) statistical tests are used for trials in which investigators are not sure are used for trials in which investigators are not sure in which direction the primary endpoint will be in which direction the primary endpoint will be affected by the intervention affected by the intervention

These tests analyze the results in both directions, for These tests analyze the results in both directions, for positive or negative effects in comparison to the positive or negative effects in comparison to the control., Two-tailed tests are more common because control., Two-tailed tests are more common because the direction of change (and the degree) is not known the direction of change (and the degree) is not known

For example, a two-tailed test is used for an For example, a two-tailed test is used for an investigational drug compared to placebo to investigational drug compared to placebo to treat elevated LDL-C treat elevated LDL-C

The investigators do not know the effect of the The investigators do not know the effect of the intervention on the LDL-C levels (i.e., the intervention on the LDL-C levels (i.e., the levels can increase or decrease relative to the levels can increase or decrease relative to the placebo). placebo).

Lab sessionLab session

How to use Mesh database to perform a How to use Mesh database to perform a targeted pubmed searchtargeted pubmed search

Use Mesh terms to search pubmed for tretment Use Mesh terms to search pubmed for tretment of paracetamol poisoning in childrenof paracetamol poisoning in children

Commonly Encountered Commonly Encountered Biomedical Literature Biomedical Literature

Case study, case report, or case Case study, case report, or case seriesseries

Case study (case report), refers to a single Case study (case report), refers to a single patient patient

case series, refers to a group of patients case series, refers to a group of patients

has no control or comparison group has no control or comparison group

simply reports on the clinical course of a simply reports on the clinical course of a particular patient or group of patientsparticular patient or group of patients

observationsobservations are described that are related to a are described that are related to a drug or technology applied to a single patient drug or technology applied to a single patient or group of patients or group of patients

an observational study, compared to n-of-1 an observational study, compared to n-of-1 trials trials

N-of-1 TrialsN-of-1 Trials

N-of-1 trials attempt to apply the principles of N-of-1 trials attempt to apply the principles of clinical trials, such as randomization and clinical trials, such as randomization and blinding, to individual patients blinding, to individual patients

An n-of-1 trial can be used to determine An n-of-1 trial can be used to determine whether a drug is effective in an individual whether a drug is effective in an individual patient patient

An n-of-1 trial can be likened to a cross-over An n-of-1 trial can be likened to a cross-over study conducted in a single subject in that a study conducted in a single subject in that a patient receives treatments in pairs (one period patient receives treatments in pairs (one period of the experimental therapy and one period of of the experimental therapy and one period of either alternative treatment or placebo) in either alternative treatment or placebo) in random order random order

N-of-1 trials may improve appropriate prescribing of N-of-1 trials may improve appropriate prescribing of drugs in individual patients. drugs in individual patients.

For example, carbamazepine may be an option for For example, carbamazepine may be an option for relief of pain in a patient with diabetic neuropathy, relief of pain in a patient with diabetic neuropathy, but definitive information on the efficacy of such but definitive information on the efficacy of such treatment is limited. Therefore, investigators may treatment is limited. Therefore, investigators may conduct an n-of-1 trial to determine whether such conduct an n-of-1 trial to determine whether such therapy is useful in a particular patient therapy is useful in a particular patient

Analytical studies/ Stability Studies Analytical studies/ Stability Studies

Stability studies determine the stability of Stability studies determine the stability of drugs in various preparations (e.g., drugs in various preparations (e.g., ophthalmologic, intravenous, topical, and oral) ophthalmologic, intravenous, topical, and oral) under various conditions (e.g., heat, freezing, under various conditions (e.g., heat, freezing, refrigeration, and room temperature)refrigeration, and room temperature)

Stability studies are extremely important to the Stability studies are extremely important to the practice of pharmacy. practice of pharmacy.

For example, pharmacists who prepare For example, pharmacists who prepare intravenous solutions for use by patients at intravenous solutions for use by patients at home often want to know how long a drug home often want to know how long a drug admixed in a particular solution is stable or if admixed in a particular solution is stable or if freezing increases the length of time an freezing increases the length of time an admixture is stable to determine how many admixture is stable to determine how many intravenous admixtures may be dispensed at a intravenous admixtures may be dispensed at a time time

It is also important for pharmacists involved It is also important for pharmacists involved with extemporaneous compounding to know with extemporaneous compounding to know the length of time a particular preparation is the length of time a particular preparation is stable. stable.

Bioequivalence StudiesBioequivalence Studies

An ever-increasing number of generic An ever-increasing number of generic products are becoming available in the products are becoming available in the marketplace marketplace

there is a need to establish that the quality, there is a need to establish that the quality, safety, and efficacy of these generic drugs are safety, and efficacy of these generic drugs are the same as the brand name product the same as the brand name product

Bioequivalence trials are often conducted Bioequivalence trials are often conducted under standardized conditions in a small under standardized conditions in a small number of normal, healthy adult volunteersnumber of normal, healthy adult volunteers

Single doses of the test and reference drugs are Single doses of the test and reference drugs are administered and blood or plasma levels of the administered and blood or plasma levels of the drug are measured over time drug are measured over time

Multidose studies are also conducted on Multidose studies are also conducted on occasion to establish bioequivalence at steady occasion to establish bioequivalence at steady state state

A two-treatment crossover study design in 24 A two-treatment crossover study design in 24 to 36 healthy adult subjects is usually used so to 36 healthy adult subjects is usually used so that the subject serves as his or her own that the subject serves as his or her own control, thus improving precision of results control, thus improving precision of results

Bioequivalent products: are products that are Bioequivalent products: are products that are equivalent in rate and extent of absorptionequivalent in rate and extent of absorption

The area under the blood concentration-time curve The area under the blood concentration-time curve (AUC) is used to assess the extent of absorption, (AUC) is used to assess the extent of absorption,

the maximum or peak drug concentration (Cmax) is the maximum or peak drug concentration (Cmax) is used to assess the rate of absorption, used to assess the rate of absorption,

these are the primary pharmacokinetic criteria used in these are the primary pharmacokinetic criteria used in bioequivalence studies. bioequivalence studies.

Observational StudiesObservational Studies

The key distinguishing feature between observational The key distinguishing feature between observational and interventional design is the inclusion or omission and interventional design is the inclusion or omission of an investigator-initiated intervention of an investigator-initiated intervention

Observational study designs do not involve an Observational study designs do not involve an intervention, rather, subject groups are based on intervention, rather, subject groups are based on presence or absence of a disease or exposure with presence or absence of a disease or exposure with observations being made and recorded regarding observations being made and recorded regarding patient characteristics patient characteristics

For instance, if an agent is particularly toxic For instance, if an agent is particularly toxic and of no therapeutic value, it would be and of no therapeutic value, it would be unethical to ask subjects to voluntarily expose unethical to ask subjects to voluntarily expose themselves to the agent, thus an observational themselves to the agent, thus an observational study would be used study would be used

An example of this type of situation is the An example of this type of situation is the evaluation of risk factors for diseases such as evaluation of risk factors for diseases such as cancer cancer

An investigator wishing to evaluate the An investigator wishing to evaluate the toxicity of environmental or industrial hazards toxicity of environmental or industrial hazards or the teratogenicity of drugs administered or the teratogenicity of drugs administered during pregnancy would have to employ during pregnancy would have to employ epidemiologic research techniques such as epidemiologic research techniques such as cohort or case-control studies to study these cohort or case-control studies to study these problems problems

Cohort StudiesCohort Studies

The cohort study—synonymously termed a The cohort study—synonymously termed a follow-up, longitudinal, or incidence study—is follow-up, longitudinal, or incidence study—is the strongest observational study design the strongest observational study design

In this design, the investigator recruits a In this design, the investigator recruits a disease-free subject population and divides the disease-free subject population and divides the population into two groups: those identified as population into two groups: those identified as either either exposedexposed or or unexposedunexposed to a factor of to a factor of interest. interest.

Subjects are then followed prospectively as Subjects are then followed prospectively as development of a disease state of interest is development of a disease state of interest is observed during the study period observed during the study period

Case-Control StudiesCase-Control Studies also termed case-referent, case history, or also termed case-referent, case history, or

retrospective studies retrospective studies

a type of observational study that offer an a type of observational study that offer an epidemiologic research alternative to cohort epidemiologic research alternative to cohort studies studies

require a large number of subjects, and are require a large number of subjects, and are often expensive and time-consuming often expensive and time-consuming

Case-control studies seek to retrospectively identify Case-control studies seek to retrospectively identify potential risk factors of diseases or outcomespotential risk factors of diseases or outcomes

subjects (cases) with a particular characteristic or subjects (cases) with a particular characteristic or outcome of interest (e.g., disease) are recruited, outcome of interest (e.g., disease) are recruited, matched with, and compared to a similar group of matched with, and compared to a similar group of subjects (controls) who have not experienced the subjects (controls) who have not experienced the characteristic or outcome.characteristic or outcome.

Data regarding exposures are collected Data regarding exposures are collected retrospectively via patient interviews or by reviewing retrospectively via patient interviews or by reviewing subject data records, and the two groups are subject data records, and the two groups are compared to identify possible risk factors compared to identify possible risk factors

Cross-Sectional Studies Cross-Sectional Studies Cross-sectional studies or prevalence studies can be thought Cross-sectional studies or prevalence studies can be thought

of as a "snapshot" because data are collected and evaluated of as a "snapshot" because data are collected and evaluated at a single point in time at a single point in time

A study is classified as cross-sectional because A study is classified as cross-sectional because measurements are taken at a single point in time, even measurements are taken at a single point in time, even though observations may cover a period of several months though observations may cover a period of several months or years or years

For example, a survey of smokers is cross-sectional when For example, a survey of smokers is cross-sectional when the questionnaire is administered once; however, the the questionnaire is administered once; however, the questions contained in the survey may focus on smoking questions contained in the survey may focus on smoking habits over the past 10 years. habits over the past 10 years.

Review ArticlesReview Articles

Review articles, consisting of analysis and Review articles, consisting of analysis and interpretation of previously conducted research interpretation of previously conducted research studies, are classified as tertiary literature studies, are classified as tertiary literature

Review articles discussing treatment of disease Review articles discussing treatment of disease states or clinical aspects of drug therapy states or clinical aspects of drug therapy enable pharmacists to gain insight into a topic enable pharmacists to gain insight into a topic or question of interest and may provide more or question of interest and may provide more current information than textbooks. current information than textbooks.

The term The term reviewreview encompasses three very encompasses three very different entities different entities

nonsystematic (narrative) reviewsnonsystematic (narrative) reviews systematic reviews (qualitative reviews), systematic reviews (qualitative reviews), meta-analyses (quantitative reviews) meta-analyses (quantitative reviews)

the purpose of review articles is to present the the purpose of review articles is to present the "truth" found among conflicting and variable "truth" found among conflicting and variable primary literature primary literature

Systematic Reviews—Quantitative Systematic Reviews—Quantitative (Meta-Analyses)(Meta-Analyses)

results of previously conducted clinical trials results of previously conducted clinical trials are combined and are combined and statisticallystatistically evaluated evaluated

Meta-analyses are designed to provide greater Meta-analyses are designed to provide greater insight into clinical dilemmas than individual insight into clinical dilemmas than individual clinical trials clinical trials

They are especially useful when previous They are especially useful when previous studies have been inconclusive or studies have been inconclusive or contradictory, or in situations where sample contradictory, or in situations where sample size may have been too small to detect a size may have been too small to detect a statistically significant difference between statistically significant difference between treatment and control groups treatment and control groups

purposes for performing a meta-purposes for performing a meta-analysis (Sacks analysis (Sacks et alet al))

(1) to increase the statistical power for primary endpoint (1) to increase the statistical power for primary endpoint and for subgroups and for subgroups

(2) to resolve uncertainty when reports disagree (2) to resolve uncertainty when reports disagree

(3) to improve estimates of size of effect(3) to improve estimates of size of effect

(4) to answer new questions not posed at the start of (4) to answer new questions not posed at the start of individual trials individual trials

(5) to bring about improvements in the quality of the (5) to bring about improvements in the quality of the primary researchprimary research

Meta-analysis has been used to address Meta-analysis has been used to address important clinical questions, such as whetherimportant clinical questions, such as whether

aspirin reduces the risk of pregnancy-induced aspirin reduces the risk of pregnancy-induced hypertension hypertension

cholesterol lowering decreases mortalitycholesterol lowering decreases mortality fluoxetine increases suicidal ideationsfluoxetine increases suicidal ideations estrogen replacement therapy increases the risk of estrogen replacement therapy increases the risk of

breast cancer. breast cancer.

Systematic Review—QualitativeSystematic Review—Qualitative

scientific investigations with predefined scientific investigations with predefined methods and original studies as their subjectsmethods and original studies as their subjects

qualitative systematic review has been applied qualitative systematic review has been applied to a summary of results of primary studies to a summary of results of primary studies where the results are where the results are notnot statistically combined statistically combined

concentrate on a clearly defined issue that is concentrate on a clearly defined issue that is of importance to practice of importance to practice

Narrative (Nonsystematic) Reviews Narrative (Nonsystematic) Reviews

A narrative (nonsystematic) review is a A narrative (nonsystematic) review is a summary of research that lacks a description summary of research that lacks a description of systematic methods of systematic methods

Narrative reviews may pertain to one specific Narrative reviews may pertain to one specific clinical question or disease state, or to topics clinical question or disease state, or to topics related to pharmacy administration related to pharmacy administration