CROSSOVER STUDY DESIGN, DESIGN OF PHARMACOKINETIC STUDIES, FACTORS INFLUENCING BIOAVAILABILITY STUDIES, STUDY DESIGN, PARALLEL DESIGN, CROSS-OVER STUDIES, LATIN SQUARE DESIN, TWO-PERIOD CROSSOVER STUDY DESIGN, BALANCED INCOMPLETE BLOCK DESIGN (BIBD), REPLICATE CROSSOVER STUDY DESIGN , DIFFERENCE BETWEEN PARALLEL AND CROSSOVER STUDY DESIGN.
Cross over design, Placebo and blinding techniques Dinesh Gangoda
A crossover design is a modified randomized block design in which each block receives more than one treatment at different dosing periods.
A block can be a patient or a group of patients.
Patients in each block receive different sequences of treatments.
A crossover design is called a complete crossover design if each sequence contains all treatments under investigation.
A placebo is a dummy medicine containing no active substance.
This substance has no therapeutic effect, used as a control in testing new drugs.
Latin- ‘ I shall please’
INSTITUTIONAL REVIEW BOARD (IRB/IEC).pptxRAHUL PAL
The International Council on Harmonisation (ICH) defines an institutional review board (IRB) as a group formally designated to protect the rights, safety and well-being of humans involved in a clinical trial by reviewing all aspects of the trial and approving its startup. IRBs can also be called independent ethics committees (IECs).
An IRB/IEC reviews the appropriateness of the clinical trial protocol as well as the risks and benefits to study participants. It ensures that clinical trial participants are exposed to minimal risk in relation to any benefits that might result from the research.
IRB/IEC members should be collectively qualified to review the scientific, medical and ethical aspects of the trial.
Per the FDA, an IRB/IEC should have:
At least five members.
Members with varying backgrounds.
At least one member who represents a non-scientific area (a lay member).
At least one member who is not affiliated with the institution or the trial site (an independent member).
Competent members who are able to review and evaluate the science, medical aspects and ethics of the proposed trial.
Clinical study on human subjects according to all guidelines to form a ideal protocol and requirement to conduct clinical trial with very efficient way mainly considering to India and ICH associated countries
Cross over design, Placebo and blinding techniques Dinesh Gangoda
A crossover design is a modified randomized block design in which each block receives more than one treatment at different dosing periods.
A block can be a patient or a group of patients.
Patients in each block receive different sequences of treatments.
A crossover design is called a complete crossover design if each sequence contains all treatments under investigation.
A placebo is a dummy medicine containing no active substance.
This substance has no therapeutic effect, used as a control in testing new drugs.
Latin- ‘ I shall please’
INSTITUTIONAL REVIEW BOARD (IRB/IEC).pptxRAHUL PAL
The International Council on Harmonisation (ICH) defines an institutional review board (IRB) as a group formally designated to protect the rights, safety and well-being of humans involved in a clinical trial by reviewing all aspects of the trial and approving its startup. IRBs can also be called independent ethics committees (IECs).
An IRB/IEC reviews the appropriateness of the clinical trial protocol as well as the risks and benefits to study participants. It ensures that clinical trial participants are exposed to minimal risk in relation to any benefits that might result from the research.
IRB/IEC members should be collectively qualified to review the scientific, medical and ethical aspects of the trial.
Per the FDA, an IRB/IEC should have:
At least five members.
Members with varying backgrounds.
At least one member who represents a non-scientific area (a lay member).
At least one member who is not affiliated with the institution or the trial site (an independent member).
Competent members who are able to review and evaluate the science, medical aspects and ethics of the proposed trial.
Clinical study on human subjects according to all guidelines to form a ideal protocol and requirement to conduct clinical trial with very efficient way mainly considering to India and ICH associated countries
The Investigator's Brochure (IB) is a comprehensive document summarizing the body of information about an investigational product (IB) obtained during a drug trial.
Introduction & Basics of DoE
Terminologies
Key steps in DOE
Softwares used for DOE
Factorial Designs ( Full and Fractional)
Mixture Designs
Response Surface Methodology
Central Composite Design
Box -Behnken Design
Conclusion
References
What are the applications of Biostatistics in Pharmacy?pharmacampus
Biostatistics broadly deals with statistical applications in the context of biological problems, including medicine, pharmacy, and public health. Government organizations, research institutes and industry have been extensively using statistics and biostatistics
Organization and objectives of ICH, expedited reporting, ICSR, PSURs, post approval expedited reporting, pharmacovigilance Planning, good clinical practices
The Investigator's Brochure (IB) is a comprehensive document summarizing the body of information about an investigational product (IB) obtained during a drug trial.
Introduction & Basics of DoE
Terminologies
Key steps in DOE
Softwares used for DOE
Factorial Designs ( Full and Fractional)
Mixture Designs
Response Surface Methodology
Central Composite Design
Box -Behnken Design
Conclusion
References
What are the applications of Biostatistics in Pharmacy?pharmacampus
Biostatistics broadly deals with statistical applications in the context of biological problems, including medicine, pharmacy, and public health. Government organizations, research institutes and industry have been extensively using statistics and biostatistics
Organization and objectives of ICH, expedited reporting, ICSR, PSURs, post approval expedited reporting, pharmacovigilance Planning, good clinical practices
It refers to the drug substance in two or more identical dosage forms , reaches systemic circulation at he same rate and to the same relative extent .
Their plasma concentration –time profile will be identical without significant statistical differences.
It refers to the drug substance in two or more identical dosage forms , reaches systemic circulation at he same rate and to the same relative extent .
Their plasma concentration –time profile will be identical without significant statistical differences.
Bioavailability & Bioequivalence Studies
https://youtube.com/vishalshelke99
https://instagram.com/vishal_stagram
Sub :- Research Methodology
M.Phrmacy Semister 1
Savitribai Phule Pune University
Bioavailability:
Bioavailability is defined as a measure, of the rate and amount of drug, which reaches the systemic circulation unchanged following the administration of a dosage form.
Absolute bioavailability:
When systemic availability of a drug administered orally
is determined in comparison to its I.V. administration, denoted by F.
Relative bioavailability:
When systemic availability of a drug after oral administration is
Compared with that of oral standard of the same drug
( Solution or suspension ) and denoted by Fr.
National Accreditation Board for Testing and Calibration Laboratories (NABL)....Durgadevi Ganesan
National Accreditation Board for Testing and Calibration Laboratories (NABL):
NABL has been established with the objective of providing Government, Industry Associations and Industry in general with a scheme of Conformity Assessment Body’s accreditation which involves third-party assessment of the technical competence of testing including medical and calibration laboratories, proficiency testing providers and reference material producers. Accreditation process details are provided in NABL 100B- Accreditation Process & Procedure.
NABL is self-financing and charges fees to Conformity Assessment Bodies to cover operational costs and other expenditure.
NABL offers accreditation services in a non-discriminatory manner. These services are accessible to all testing including medical and calibration laboratories, proficiency testing providers and reference material producers in India and other countries in the region, regardless of the size of the applicant CAB or its membership of any association or group or number of CABs already accredited by NABL. Applicable fees details are provided in NABL 100A- General Information Brochure.
SERVICES PROVIDED BY NABL:
Testing laboratories in accordance with ISO/ IEC 17025 ‘General Requirements for the Competence of Testing and Calibration Laboratories’
Calibration laboratories in accordance with ISO/ IEC 17025 ‘General Requirements for the Competence of Testing and Calibration Laboratories’
Medical testing laboratories in accordance with ISO 15189 ‘Medical laboratories -Requirements for quality and competence’
Proficiency Testing Providers (PTP) in accordance with ISO/IEC 17043 “Conformity assessment — General requirements for proficiency testing” and
Reference material producers (RMP) in accordance with ISO 17034 “General requirements for the competence of reference material producers”.
BENEFITS OF NABL CERTIFICATION:
Increased trust in Testing/ Calibration Reports issued by the research facility.
Better control of research facility activities and criticism to labs concerning whether they have a sound Quality Assurance System and are actually skilled.
Potential expansion in business because of improved client certainty and fulfillment.
Customers can look and recognize the research centers licensed by NABL for their particular prerequisites from the NABL Web - webpage or Directory of Accredited Laboratories.
Users of certified research facilities appreciate more noteworthy access for their items, in both domestic and international markets.
Savings in terms of time and money due to reduction or elimination of the need for retesting of products.
Increased trust in Testing/ Calibration Reports issued by the research facility.
Better control of research facility activities and criticism to labs concerning whether they have a sound Quality Assurance System and are actually skilled.
Potential expansion in business because of improved client certainty and fulfillment.
NABL ACCREDITATION PROCESS
DEFINITION,PRINCIPLE, OBJECTIVES, ELEMENTS AND TOOLS OF QUALITY BY DESIGN (Qb...Durgadevi Ganesan
Quality by Design is a concept first outlined by Joseph M. Juran in various publications. He supposed that quality could be planned. The concept of QBD was mention in ICH Q8 guidelines, which states that, “To identify quality can not be tested in products, i.e. Quality should be built in to product by design.”
What is Quality by Design (QbD)?
Quality by Design (QbD) is a strategic approach employed in various industries, including pharmaceuticals, manufacturing, and product development, to ensure the consistent delivery of high-quality products.
Why QbD?
Principle of QbD
Objectives of QbD
ELEMENTS OF PHARMACEUTICAL QUALITY BY DESIGN:
- Quality Target Product Profile
- Critical Quality Attributes
- Product Design and Understanding
- Process Design and Understanding
- Process Design and Understanding
- Design space
- Control Strategy
- Continual Improvement
DESIGN TOOLS
- Prior Knowledge
- Risk Assessment
- Mechanistic Model, Design of Experiments, and Data Analysis
- Process Analytical Technology
OVERVIEW, BENEFITS, ELEMENTS AND STEPS FOR REGISTRATION OF ISO 9000 & ISO 140...Durgadevi Ganesan
INTERNATIONAL STANDARDS ORGANIZATION: ISO 9000 & ISO 14000.
- DEFINITIONS OF ISO 9000 & ISO 14000.
- OVERVIEW OF ISO 9000 & ISO 14000.
- BENEFITS OF ISO 9000 & ISO 14000.
- ELEMENTS OF ISO 9000 & ISO 14000.
- STEPS FOR REGISTRATION AND CERTIFICATION OF ISO 9000 & ISO 14000.
- ISO AUDITS OF ISO 9000 & ISO 14000.
- ISO 9000 STANDARDS:- 9000, 9001, 9004 AND 19011.
- ISO 14000 STANDARDS:- 14001, 14002, 14004, 14015, 14016, 14017, 14020, 14021, 14024, 14030, 14031, 14040 AND 14043.
- DIFFERENCE BETWEEN ISO 9000 AND 14000.
ICH STABILITY TESTING GUIDELINES (ICH Q1A-Q1F).pptxDurgadevi Ganesan
ICH Stability Testing Guidelines: ICH Q1A-Q1F (Q1 series)
Q1A(R2): STABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTS
Q1B: PHOTOSTABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTS
Q1C: STABILITY TESTING FOR NEW DOSAGE FORMS
Q1D: BRACKETING AND MATRIXING DESIGNS FOR STABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTS
Q1E: EVALUATION OF STABILITY DATA
Q1F: STABILITY DATA PACKAGE FOR REGISTRATION APPLICATIONS IN CLIMATIC ZONES III & IV
Contents:
Vitamins: Definition
Classification of vitamins.
Fat soluble vitamins: Vitamin A, Vitamin D, Vitamin E and Vitamin K. Chemical nature, Dietary sources, Coenzyme forms, Biochemical functions, recommended dietary allowances and deficiency diseases of fat soluble vitamins.
CLINICAL SIGNIFICANCE OF BIOEQUIVALENCE STUDIES, BIOEQUIVALENCE, REASONS TO PERFORM BIOEQUIVALENCE STUDIES , NEED FOR BIOEQUIVALENCE STUDIES, IMPORTANCE OF BIOEQUIVALANCE STUDIES, DETERMINATION OF BIOEQUIVALENCE OF A DRUG PRODUCT, CLINICAL SIGNIFICANCE.
Rationale for the reporting and control of degradationDurgadevi Ganesan
Rationale for the reporting and control of degradation, Reporting procedure, Identification of degradation products, Threshold for degradation products in new drug products, Analytical procedure, Reporting degradation products contents of batches.
Mass spectrometry, Categories of ion sources, Ionization techniques, Electron Impact ionization (EI), Chemical ionization, Field ionization, Fast atom bombardment (FAB), Matrix associated laser desorption ionization (MALDI), Atmospheric pressure chemical ionization (APCI), Electrospray ionization (ESI) and Atmospheric pressure photo ionization (APPI).
Dissolution : Official and Non official methods, Alternative methods of dissolution testing and transport models, Drug release testing, Invitro drug release testing
Mass analyzers : Quadrupole mass analyzer, time of flight mass analyzer, fourier transform ion cyclotron resonance(FT-ICR), ion trap mass analyzer(3D ion trap and 2D ion trap), orbitrap mass analyzer.
Patent and its types, rights and responsibilities of patentee, filing patent applications, patent application forms and guidelines, types of patent applications.
A Strategic Approach: GenAI in EducationPeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
Embracing GenAI - A Strategic ImperativePeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Honest Reviews of Tim Han LMA Course Program.pptxtimhan337
Personal development courses are widely available today, with each one promising life-changing outcomes. Tim Han’s Life Mastery Achievers (LMA) Course has drawn a lot of interest. In addition to offering my frank assessment of Success Insider’s LMA Course, this piece examines the course’s effects via a variety of Tim Han LMA course reviews and Success Insider comments.
Biological screening of herbal drugs: Introduction and Need for
Phyto-Pharmacological Screening, New Strategies for evaluating
Natural Products, In vitro evaluation techniques for Antioxidants, Antimicrobial and Anticancer drugs. In vivo evaluation techniques
for Anti-inflammatory, Antiulcer, Anticancer, Wound healing, Antidiabetic, Hepatoprotective, Cardio protective, Diuretics and
Antifertility, Toxicity studies as per OECD guidelines
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
The Roman Empire A Historical Colossus.pdfkaushalkr1407
The Roman Empire, a vast and enduring power, stands as one of history's most remarkable civilizations, leaving an indelible imprint on the world. It emerged from the Roman Republic, transitioning into an imperial powerhouse under the leadership of Augustus Caesar in 27 BCE. This transformation marked the beginning of an era defined by unprecedented territorial expansion, architectural marvels, and profound cultural influence.
The empire's roots lie in the city of Rome, founded, according to legend, by Romulus in 753 BCE. Over centuries, Rome evolved from a small settlement to a formidable republic, characterized by a complex political system with elected officials and checks on power. However, internal strife, class conflicts, and military ambitions paved the way for the end of the Republic. Julius Caesar’s dictatorship and subsequent assassination in 44 BCE created a power vacuum, leading to a civil war. Octavian, later Augustus, emerged victorious, heralding the Roman Empire’s birth.
Under Augustus, the empire experienced the Pax Romana, a 200-year period of relative peace and stability. Augustus reformed the military, established efficient administrative systems, and initiated grand construction projects. The empire's borders expanded, encompassing territories from Britain to Egypt and from Spain to the Euphrates. Roman legions, renowned for their discipline and engineering prowess, secured and maintained these vast territories, building roads, fortifications, and cities that facilitated control and integration.
The Roman Empire’s society was hierarchical, with a rigid class system. At the top were the patricians, wealthy elites who held significant political power. Below them were the plebeians, free citizens with limited political influence, and the vast numbers of slaves who formed the backbone of the economy. The family unit was central, governed by the paterfamilias, the male head who held absolute authority.
Culturally, the Romans were eclectic, absorbing and adapting elements from the civilizations they encountered, particularly the Greeks. Roman art, literature, and philosophy reflected this synthesis, creating a rich cultural tapestry. Latin, the Roman language, became the lingua franca of the Western world, influencing numerous modern languages.
Roman architecture and engineering achievements were monumental. They perfected the arch, vault, and dome, constructing enduring structures like the Colosseum, Pantheon, and aqueducts. These engineering marvels not only showcased Roman ingenuity but also served practical purposes, from public entertainment to water supply.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
Instructions for Submissions thorugh G- Classroom.pptxJheel Barad
This presentation provides a briefing on how to upload submissions and documents in Google Classroom. It was prepared as part of an orientation for new Sainik School in-service teacher trainees. As a training officer, my goal is to ensure that you are comfortable and proficient with this essential tool for managing assignments and fostering student engagement.
Acetabularia Information For Class 9 .docxvaibhavrinwa19
Acetabularia acetabulum is a single-celled green alga that in its vegetative state is morphologically differentiated into a basal rhizoid and an axially elongated stalk, which bears whorls of branching hairs. The single diploid nucleus resides in the rhizoid.
2. DESIGN OF PHARMACOKINETIC
STUDIES
The main object of the experimental design is to minimize
the experimental variables and to avoid a bias.
In vivo bioavailability study is determined by taking into
consideration of the following points:
The nature of the reference drug and the dosage form to be
tested
Benefit risk ratio considerations in regard to testing in
humans
The availability of analytical methods
What is the scientific questions to be answered?
3. FACTORS INFLUENCING
BIOAVAILABILITYSTUDIES
Bioavailability studies are influenced by various factors such as
Age
Sex
disease state
food habits
physical and mental health condition
body weight human volunteer
experimental design
time of administration
time of sampling
analytical method used
Compartment model used in estimating pharmacokinetic parameters or
bioavailability that contribute to the observed blood concentration time
profile.
4. STUDY DESIGN
The bioavailability study should be designed in such a
way that the formulation effect can be distinguished from
other effects.
If two formulations are to be compared, a two-period,
two-sequence crossover design is the design of choice
which should ideally be equal to or more than five half-
lives that have to be measured
Alternative study designs include the parallel design for
very long half-life substances with highly variable
disposition.
5. PARALLEL DESIGN
In a parallel design, two formulations are administered to two groups
of volunteers.
To avoid a bias, formulations may be administered randomly to the
volunteers.
The major disadvantage of this design is that the intersubject variation
is not being corrected.
It has been proved beyond doubt that most of the times intersubject
variation is greater than the variation between any formulation.
Therefore, a cross over design is preferred in bioavailability or
bioequivalence trails to avoid influence of a intersubject variation.
This design is used mainly for drug, and its metabolites have long
elimination half-life.
The carryover effects or dropouts were less in parallel studies
compared to crossover studies.
6. C0NTI...
A parallel study is also referred to as “between patient” or “non-
crossover” study.
It is defined as a type of clinical study, in which two separate
treatment arms, A and B, are given so that one group receives only
treatment arm A while another group receives only treatment arm B.
The two treatment groups of a parallel study can either be composed
of two completely separate treatments (i.e. different drugs), or simply
different doses of the same drug.
A major characteristic of a parallel study is randomization, which
ensures accuracy of the results and lower risk of being biased.
Generally, a placebo or active control are used as control groups in
parallel studies.
7.
8. CROSS-OVER STUDIES
In crossover studies, the study participants will be switched
throughout to all the treatment groups (both test and reference
formulations) after a washout period.
Being the same set of the population the advantage of crossover
studies is that patients act as their own controls.
Bioavailability (BA)/BE studies are usually conducted as
crossover studies.
BE studies can be conducted under fasting and fed conditions.
The sampling time points and the duration of BE studies
depend on the half-life of the drug of interest.
In the case of a feeding study, a high-fat, high-calorie breakfast
would be provided to the subjects before administration of
investigational product (IP).
9. CONTI…
As recommended by the USFDA, in most bioequivalence
studies, a test drug is compared with the standard
reference drug in a group of normal healthy subjects of
age 18–55 years, each receives both the treatments
alternately, in a crossover fashion (two-period, two-
treatment crossover design), with the two phases of
treatment separated by a washout period of generally a
week’s duration and it mainly depends on the half-life of
the drug.
If elimination half-life of the drug increases, the washout
period also increases.
10. CONTI…
The drug formulation either test or reference is given to each human
volunteer randomly but an equal number of subjects receives each
treatment in each period.
In case of two treatments, groups 1 and 2, one group receives the
treatment in the order A and B, and the second group receives in the
reverse order B and A.
A similar allocation is done in case of a three-treatment crossover
design (three-period, three-treatment crossover design)
Intersubject variability is observed for several drugs in clearance.
The intrasubject coefficient of variation (approximately 15%) is
usually substantially smaller than that between subjects
(approximately 30%), and therefore crossover designs are generally
recommended for bioequivalence studies.
11. CONTI…
In crossover design, the treatments are compared on the same human
subject, and the intersubject variability is reduced.
Both the designs depend on the three fundamental statistical concepts
of study design, and these are randomization, replication, and error
control.
Randomization means allocation of treatments to the subjects without
bias.
Replication involves the application of more than one experimental
subject for reliable estimates than a single observation and also
provides a more precise measurement of treatment effects.
The number of replicates required mainly depends upon the degree of
differences to be detected and inherent variability of the data.
12.
13. Commonly used cross over designs
Commonly used cross over designs in
bioavailability trails are
Latin square cross over design
Balanced incomplete block design
Replicate Crossover-study design
14. LATIN SQUARE DESIN
The Latin-square design plans the clinical trial so that each subject
receives each drug product only once, with adequate time between
medications for the elimination of the drug from the body.
In this design, each subject is his own control, and subject-to-subject
variation is reduced.
Moreover, variation due to sequence, period, and treatment
(formulation) are reduced, so that all patients do not receive the same
drug product on the same day and in the same order.
Possible carryover effects from any particular drug product are
minimized by changing the sequence or order in which the drug
products are given to the subject.
Thus, drug product B may be followed by drug product A, D, or C .
After each subject receives a drug product, blood samples are
collected at appropriate time intervals so that a valid blood drug level–
time curve is obtained.
15. CONTI…
The time intervals should be spaced so that the peak blood
concentration, the total area under the curve, and the absorption
and elimination phases of the curve may be well described.
The crossover design is a type of Latin square. In a Latin square
the number of treatments equals the number of patients.
In addition, another factor, such as order of treatment, is
included in the experiment in a balanced way.
The net result is an N X N array (where N is the number of
treatments or patients) of N letters such that a given letter
appears only once in a given row or column. This is most easily
shown pictorially.
16. Two-Period Crossover Design
For randomizations of treatments in Latin squares, For the comparison
of two formulations, a 2 X 2 Latin square (N = 2) consists of two
patients each taking two formulations (A and B) on two different
occasions in two “orders”.
The balancing of order (A-B or B-A) takes care of time trends or other
‘‘period’’ effects, if present. (A period effect is a difference in response
due to the occasion on which the treatment is given, independent of
the effect due to the treatment).
The 2 X 2 Latin square shown above is familiar to all who have been
involved in bioavailability/bioequivalence studies. In these studies, the
2 X 2 Latin square is repeated several times to include a sufficient
number of patients. Thus the crossover design can be thought of as a
repetition of the 2 X 2 Latin square.
17. CONTI...
2 formulations, even number of subjects, randomly
divided into 2 equal groups.
First period , each member of one group receive a single
dose of the test formulation; each member of the other
group receive the standard formulation.
After a wash period (5 half lives), in second period , each
member of the respective groups will receive an
alternative formulation & experiment will be repeated.
19. Incomplete block design (BIBD)
More than 3 formulations, Latin square design will not be ethically
advisable. Because each volunteer may require drawing of too many
blood samples. If each volunteer expected to receive at least two
formulation, then such a study can be carried out using BIBD.
It eliminates many of the difficulties encountered with the Latin
square design.
In this, each subject receives not more than two formulations, each
formulation is administered the same number of times and each pair of
formulations occurs together in the same number of subjects.
In this design, as discussed above, each subject receives two
formulations, each formulation is administered six times and each pair
of formulations occurs together in two subjects (the pairs are AB, AC,
AD, BC, BD, and CD).
21. Replicate Crossover-study design
For highly variable drugs.
It allows comparisons of within-subject variances.
It reduces the number of subjects needed.
Four-period, two-sequence, two-formulation design
(recommended) or Three-sequence, three-period, single-
dose, partially replicated.
Replicated crossover designs are used for the
determination of individual bioequivalence, to estimate
within-subject variance for both the Test and Reference
drug products, and to provide an estimate of the subject-
by-formulation interaction variance.
Generally, a four-period, two-sequence, two-formulation
design is recommended by the FDA.
22. PERIOD 1 2 3 4
GROUP 1 T R T R
GROUP 2 R T R T
Where,
R = reference
T = treatment
The same reference and the same test are each given twice to the same
subject. Other sequences are possible. In this design, Reference-to-
Reference and Test-to-Test comparisons may also be made.
23. DIFFERENCE BETWEEN PARALLEL
AND CROSSOVER STUDY DESIGN
PARALLEL STUDY DESIGN CROSSOVER STUDY DESIGN
Groups assigned different treatments Each patient receives both treatments
Shorter duration Longer duration
Sample size is large Sample size is smaller
No carryover effect Carryover effect
Acute cases Not in acute cases
Doesn’t require stable disease and
similar baseline
Requires stable disease and similar
baseline
24. PARALLELVS CROSS-OVER DESIGN
PARALLEL DESIGN CROSS-OVER DESIGN
ADVANTAGES
Easy to organize
Easy to analyze
Easy to interpret
DISADVANTAGES
Comparison is carried out between
subjects: Not very powerful
ADVANTAGES
Comparison is carried out within and
between subjects: Much powerful
Each cross-over patient serves as his
or her own control.
DISADVANTAGES
Unsuitable for long half life drugs
Carry-over effect due to
inappropriate wash-out.
Order effects the results.
Difficult to analyze
Takes long time to complete
Not optimal for study in patients