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Annals of Clinical and Medical
Case Reports
Mini Review ISSN 2639-8109 Volume 8
Bio-Statistics Newer Advances, Scope & Challenges in Bio-Medical Research
Murthy NS1
, Kunnavil R2
and Shivaraj NS3
1
Former Research Director, DRP and Professor and Research Coordinator, M.S. Ramaiah Medical College & Hospitals (MSRMC),
Bangalore, India.
2
Lecturer in Biostatistics, National Institute of Unani Medicine, Bangalore, India
3
Assistant professor Statistics, Department of Community Medicine, M.S. Ramaiah Medical College & Hospitals (MSRMC), Banga-
lore, India
*
Corresponding author:
Radhika Kunnavil.
Lecturer in Biostatistics, National Institute of
Unani Medicine, Bangalore- 560091, India,
Tel: 7829606040,
E-mail: radhik121@gmail.com
Received: 25 Feb 2022
Accepted: 09 Mar 2022
Published: 14 Mar 2022
J Short Name: ACMCR
Copyright:
©2022 Kunnavil R. This is an open access article dis-
tributed under the terms of the Creative Commons Attri-
bution License, which permits unrestricted use, distribu-
tion, and build upon your work non-commercially.
Citation:
Kunnavil R, Bio-Statistics Newer Advances, Scope &
Challenges in Bio-Medical Research. Ann Clin Med
Case Rep. 2022; V8(14): 1-7
Keywords:
Biostatistics; Bio-medical research; Scope; Appli-
cations; challenges
http://www.acmcasereport.com/ 1
1. Abstract
Biostatistics also known as biometry which means ‘measurement
of life’is a branch of applied statistics which deals with collection,
compilation, analysis and interpretation of data related to biomed-
ical sciences. It provides a key to better understanding of the med-
ical discipline. Biological data are always subjected to variation
and are affected by various environmental, social and genetic fac-
tors etc. Biostatistics proves a tool for analysing the data taking
into account the variability and to elicit meaningful conclusion in
research. In this era of evidence-based medicine. Nowadays, the
discipline of biostatistics acts as a basic scientific entity of public
health, health services and biomedical research. Biostatistics has
evolved as a branch of science in biomedical research that uses a
combination of statistics, probability, mathematics and computing
to resolve perplexing questions mathematically. Because research
questions in biology and medicine are diverse, biostatistics has
expanded its domain to include any complex quantitative model
to answer research questions. Biostatistics has reach in wide spec-
trum of biomedical domains. From drug development in a labo-
ratory to development of various disease control and prevention
measures at community level and a lot more. The important aspect
for biostatistics is that it helps in valid clinical decision making by
elucidating and quantifying the contribution of chance. Overtime
this field has expanded its wings and now it is widely used across
many systems of medicine including Ayurveda, Unani etc. The
computer programmes and advent of newer methods has increased
its scope and applications. This paper aims to through light on the
newer advances in biostatistics. This paper explores the newer
methods, scope & few challenges in Bio-Medical Research.
2. Introduction
Bio-statistics has pivotal role in the development of medical and
biological sciences as well as in the development of various dis-
ease control and prevention measures. Nowadays, the discipline
of biostatistics acts as a basic scientific entity of public health,
health services and biomedical research. Over the last few de-
cades, bio-statistics have become more quantitative, stochastic,
evidenced based with the growth of medical sciences and public
health-oriented research. Emerging disciplines such as Machine
learning, Clinical Epidemiology, Molecular Biology, Genomics
and Pharmacokinetics have all contributed to making medical
and health sciences depend more and more on Biostatistics. The
present write-up focusses on role and use of bio-statistics in the
epidemiology, bio-medical research as well as some to touch upon
newer methods, scope & few challenges in Bio-Medical Research.
3. Bio-Statistics as a Stream
Over the last few decades, the development of statistical methods
has expanded. Statistics applied to medical research – biostatis-
tics – may now be regarded a subject in its own right, research
in medicine and public health has been both a benefactor and a
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Volume 8 Issue 14 -2022 Mini Review
source of new difficulties as a result of this new technique. In re-
ality, biostatistics has evolved into a distinct field of study that
solves issues in the biological sciences by combining statistics,
probability, mathematics, and computing. Biostatistics has broad-
ened its area to encompass any quantitative, not just statistical,
model that may be used to answer these issues, due to the diversity
of research questions in biology and medicine. Biostatistics is a
field that aims to provide information. Consequently, biostatistics
draws quantitative methods from fields including statistics, oper-
ations-research, economics, and mathematics in general; and it is
applied to research questions in fields such as epidemiology, nutri-
tion, environmental health, and health services research, genomics
and population genetics, clinical medicine, and ecology.
The significance of biostatistics and biostatisticians in medical re-
search has long been acknowledged by the biomedical communi-
ty, and statistics in medicine may now be regarded a successful
paradigm for the incorporation of statistics into scientific practice.
The relevance of biostatisticians in the biomedical profession may
be seen in the fact that they are frequently asked to contribute as
advisers on renowned committees and journals. Furthermore, spe-
cific statistical publications such as Biostatistics, Biometrics, Bio-
metrika, and many other biostatistics-related journals are held in
high esteem [1-2].
4. Types of Research Investigations in Bio-Medical
Field
Quality biomedical research is based on a foundation of careful
study design. Over the last several decades, newer and innovative
concepts and statistical methods for the design and analysis of data
in biological studies have been established and are being used. De-
sign of studies such as case-control studies, cohort studies, clinical
trials, and survival studies has been the center of development. The
application of epidemiologic ideas and techniques to the design,
conduct, and analysis of clinical trials is a major development,
with comprehensive applications described in the following para-
graphs. Observational and experimental research studies are the
two categories of scientific research studies in biomedical field.
Selection of subjects on whom measurements are made is one of
the most essential problems that occur during the formulation of
statistical methods of research [3-5].
5. Why is Statistics Necessary in Bio-Medical Field?
Without appropriate inferences, empirical research in any field
is incomplete, and biomedical research is no exception. Both the
design of diverse biomedical research investigations and the eval-
uation of outcomes need the use of proper statistical tools. Biosta-
tistics has now become a crucial component in several research
domains as a result of expansion of quantitative approaches with
in biomedical sciences (bio-chemical, physiological, clinical pa-
rameters, or evidence-based medicine). Medicine is a science in
which chance plays an important role. Statistics as a science aid in
quantifying the role of chance, whereas statistics as an art aids in-
dividual clinicians in making accurate diagnostic, prognostic, and
therapeutic judgments. It also aids health programme administra-
tors and policymakers in the planning, monitoring, and evaluation
of public health efforts. A health indicator can be used to describe
one or more aspects of an individual's or population's wellbeing
(quality, quantity, and time), and also to define public health prob-
lems at a specific moment in time, to indicate changes in levels of a
population's or individual's health over time, to define distinctions
in population health, and to assess the extent to which a program's
objectives are being met. Similarly, validity metrics including sen-
sitivity, specificity, positive and negative predictive value are used
to evaluate the quality and usefulness of a diagnostic test or to
determine the efficiency of a marker in disease diagnosis [3].
5.1. Epidemiology and Biostatistics
Epidemiology is the branch that studies diseases occurrence and
its reasons in different groups of people. Epidemiological data is
used to design and evaluate disease prevention initiatives, as well
as to guide the treatment of patients who already developed disease.
Biostatistics and epidemiology have historically had such a signif-
icant link. The early public health experts were doctors basically
keen to understand the path wherein ailments eventuate in popula-
tions, their causes, as well as their interrelations with various med-
ical and non-medical aspects. These innovators' challenges includ-
ed not just the study of epidemics and non-communicable diseases
such as the connection between smoking and lung cancer, but also
the evaluation of therapies. Many had strong analytical reasoning
abilities and were well-versed in statistical methods. Then, begin-
ning in the 1930s, epidemiology began focusing upon that study
of chronic diseases. The same prospective research strategies that
had been so clearly appropriate in the study of infectious diseases
became untenable. And it was statisticians, particularly Cornfield
and Mantel, who provided a rationale for clarify case-control in-
ference. With concerns about bias related to possible confounding
factors, biostatisticians have become more interested in growing on
the prerequisites for valid inference. They also began searching at
other areas of epidemiological research, including models for eval-
uating the effects of potential disease risk factors, such as dose re-
sponse models. These effects are quantified employing probabilis-
tic notions such as the odds ratio or relative risk, which can be es-
timated appropriately based on the type of study (case-con-
trol, cross sectional, or cohort) used for each research proj-
ect. The large number of statistical methods required in epidemi-
ology has led to the publication of numerous books on statisti-
cal applications in epidemiological contexts [6-9].
5.2. Clinical trials and biostatistics
Clinical studies are a crucial component of medical research. Sci-
entific advance can lead to better ways of diagnosing, detecting,
and treating diseases and medical conditions as a consequence of
these clinical studies. Clinical trials are research studies which use
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Volume 8 Issue 14 -2022 Mini Review
human subjects to evaluate novel therapies or drug combinations,
modern surgical or radiotherapy approaches, or new procedures
in order to improve illness diagnosis or quality of life for patients.
Most hospitals now participate in drug testing, which are only
started once laboratory investigations show that a new treatment
or technique is safe and also has the potential to be more efficient
than existing options. Statistics have become increasingly import-
ant in the field of pharmaceutical development in recent years.
From planning through conduct and interim analysis to final anal-
ysis and reporting, statistics is essential at each and every stage
of a clinical trial [10-11]. The statistician is typically in responsi-
ble for formulating randomization schedules, advising on sample
size, establishing framework for deciding treatment differences,
and evaluating response rates. In most instances, the statisticians
will also act as a liaison with the Independent Data Monitoring
Committee. Several novel and recurring challenges in the drug
development process require special attention. Ongoing develop-
ment of statistical methods for handling subgroups in the design
and analysis of clinical trials; alternatives to "intention-to-treat"
analysis in the presence of noncompliance in randomized clinical
trials; methodologies to address the multiplicities resulting from
a variety of sources, methods to assure data integrity etc all of
which are inherent in the drug development process. These con-
cerns continue to be a source of contention for statisticians work-
ing in the pharmaceutical industry across the world. Furthermore,
the engagement of statisticians from all backgrounds continues
to enrich the profession and contribute to social health improve-
ments. Biostatisticians' significant methodological contributions to
clinical trials research has led to the development of a new journal,
Pharmaceutical Statistics, which was just published in 2002 and
is already placed in the JCR ranking for Statistics and Probability.
6. Advanced Statistical Areas of interest in Bio-Medical
Field
In addition to routine descriptive and inferential statistics, gen-
eralised linear models, survival analysis, and Bayesian methods
etc have already had a significant impact on the medical statistics
in recent years (in diagnostic, epidemiological and clinical trials
contexts). Regression analysis or linear discriminant analysis are
statistical approaches used in the biomedical profession to predict
a dependent variable using additional independent variables/ fea-
tures or to divide persons into two or more classes of objects or
events based on illness status. The approaches outlined above have
aided in the reduction of dimensionality as well as the classifying
of people as sick or non-diseased [7-13].
7. Modeling-Approach in Epidemiological Research/
Bio-Medical Filed - Generalized Linear Models
Modeling of health and disease process has been a complex phe-
nomenon. Several models have been employed for the analysis
and interpretation of data in the biological field. In the forgoing
sections, it is proposed to describe three different types of general
linear models which have been extensively employed as multi-
variate procedures in bio-medical field viz. (i) Age-period cohort
models, (ii) Logistic regression model and (iii) Survival analysis.
7.1. Importance of time-related analysis
Cancer incidence/mortality rates from population-based registries
(which gather data on all cancer cases in specified areas) give in-
formation on regional and temporal variation in cancer risk by
personal variables including age, sex, and racial or ethnic group-
ings. "Time," the third element of an epidemiological description,
provides information on geographic areas and serves as the foun-
dation for determining how effective cancer-prevention methods
are. Changes in cancer pattern over time are of critical importance
in cancer control efforts. Age at risk, calendar year, and birth co-
hort impact are the most often evaluated time-related confounders.
The trend analysis helps to understand the question such as how
cancer risk has been changing, why and what is likely to happen
in future. Cancer trend analysis is important information for the
public health and health care planning. Trend analysis reveals in-
formation on the disease's aetiology and the significant variance in
its prevalence across different geographic areas. Cancer incidence/
mortality trends can also be used to forecast future cancer patterns,
which can help shape future public health policy. The suitable tools
for assessing trends in cancer incidence/mortality data include data
modelling by age, birth cohort, and calendar time period. "Age-pe-
riod-cohort (ACP) models" are the name for these models. These
models are based on regression models with a Poisson distribu-
tion [14].Using the data from the Indian Population Based Cancer
Registries for the past twenty-five years, the aforesaid modelling
approach was used to predict the changes in the incidence of com-
mon malignancies. Some malignancies, such as breast, ovarian,
corpus, and uterus, were found to be rising at a rate of around 1-2
percent every year, according to the research, and the similar trend
was seen in women of a younger age range [15-18].
7.2. Modelling of the data in case of binary outcome event
When the dependent variable (outcome variable) is binary in na-
ture, such as whether an event occurs or not, taking values of unity
or zero, the assumption required for fitting a multiple linear re-
gression model of the type Y= α +Σk
i=1
βXi
is violated because it
is unreasonable to assume that error distribution is normal. Mul-
tiple logistic regression analysis (LR) is used as a multivariate
approach to discover the independent predictors of the outcome
variable instead of multiple linear regression analysis. The key
difference between LR and multiple linear regression models is
that instead of utilising the dependent variable as is, we utilise a
model based on the dependent variable's logit transformation to
meet the required assumptions. As a result, in the LR model, we
forecast the proportion of subjects (P) who have a specific charac-
teristic, or, alternatively, the probability of having characteristics
for any combination of explanatory factors [8,19,20]. A dichoto-
mous outcome variable is linked to a set of "k" known or suspected
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Volume 8 Issue 14 -2022 Mini Review
causes (regression variables), as well as probable confounding and
effect modification variables, in this model. Covariates or explan-
atory variables are a collection of k regression variables or risk
factors. The approach of maximum likelihood estimation is used
to estimate the unknown parameters in the model, α, and βi
. In
most cases, the likelihood inference is preceded by the fitting of
a hierarchy of models, each of which contains the last variable.
The likelihood ratio test or a test based on Wald statistics are used
to test the hypothesis. This modelling approach was used to find
independent risk variables linked to illness or a negative outcome
event. The logistic regression approach was used in research to
look at the impact of maternal and perinatal outcomes in different
degrees of anaemia. Mild anaemia had the best maternal and peri-
natal outcomes, according to the research. Low birth weight kids,
induction rates, surgical deliveries, and protracted labour have all
been linked to severe anaemia [21].
7.3. Studies on survival analysis
Understanding the link between time and the occurrence of vital
and health-related events requires the study of lifetime data. In the
biomedical area, time-to-event data is regularly encountered for
study. This type of study is known as "survival analysis." The time
passed between a subject's enrollment into the research and the
occurrence of an event that is related to treatment is the outcome
variable in follow-up/survival studies. The outcome variable has
been dubbed survival time, and the event of interest (the onset of
a disease) has been dubbed failure. In oncology, for example, the
focus is usually on the patient's chance of survival after a surgical
procedure. Issues of censoring and truncation hamper the analysis
of this sort of survival trial.
The analysis of lifetime data is important in understanding the re-
lationship between time and occurrence of vital and health related
events. Time-to-event data is frequently encountered for analysis
in bio-medical field. Such analysis is called as "survival analysis".
In follow-up/ survival studies, the outcome variable is the time
elapsed between the entry of a subject into the study and the oc-
currence of an event is related to treatment. The event of interest
(development of a disease, death) has been referred to failure and
the outcome variable as the survival time. In oncology, for exam-
ple, interest typically centers on the patient’s time of survival fol-
lowing a surgical intervention. The analysis of this type of survival
experiment is complicated by issues of censoring and truncation.
Censoring occurs when we do not fully observe the patient’s sur-
vival, due to death unrelated to the cancer under study, or dis-
appearance from the study for some reason. The other factor is
truncation, which basically occurs when some patients can’t be
observed for some reasons related to the survival itself. A common
example of this is in HIV/AIDS studies of the incubation period
(i.e., time from infection to disease). The follow-up starts when
the HIV virus is detected and the moment of infection is retro-
spectively ascertained. Several survival parametric models such as
Exponential and Weibull distributions were introduced to model
the survival experience/follow-up data analysis of homogeneous
populations incorporating the censoring schemes. The distribution
of survival times must be known to apply these models. However,
when the distribution of survival is not known, the non-parametric
method of Kaplan-Meier curve developed in 1959 has been a well-
known estimator of the survival function, and it is extensively used
in epidemiological and clinical research [20-24].
In order to take into account diversity of situations, which were
encountered in practice, Cox in 1972 developed a modelling pro-
cedure termed as Cox-proportional hazards model under a very
rigorous theoretical backup. The classical proportional hazards
model of Cox (1972) is also widely used whenever the goal is to
study how covariates affect survival. This model is an important
tool in the follow-up/survival studies for modelling the effect of
risk factors/prognostic factors when the outcome of interest occurs
with time. In the model, the hazard for an individual is a part of
the product of a common baseline hazard and a function of set of
risk factors. By applying the above modelling procedure, the in-
dependent risk factors associated with the development of precan-
cerous lesions of cancer of cervix was evaluated [25]. Similarly,
in another study the treatment effectiveness for curing of a gastro
intestinal bleeding was evaluated which employed an experimen-
tal design [26]. However, when the assumption of proportionality
does not satisfy, then a classical approach for the analysis of data
of this type is the time-dependent Cox regression model (TDCM).
Advantages of Cox’s regression model include its easy interpret-
ability and its availability in the majority of statistical packages.
7.4. New issues in survival analysis
When survival is the ultimate result yet intermediate phases are
discovered, a generalisation of the survival process occurs. In
this case, a series of occurrences is witnessed, resulting in many
observations per person. Intermediate stages might be based on
categorical time-dependent factors like transplantation, clinical
symptoms (e.g., bleeding episodes), or a complication during the
disease (e.g., metastases), or biological markers (like CD4T-lym-
phocyte levels). Multi-state models (MSMs) were accessible in the
1990s, allowing for a better grasp of the disease process and a bet-
ter comprehension of how the time dependent covariate impacts
the illness's evolution. Compared to Cox's regression model, these
contemporary models offer significant advantages. They provide
a better understanding of the illness process by indicating the risk
of moving from one condition to another (transition intensities), as
well as a variety of additional data, such as the average time spent
in each state and survival rates for each stage. Differences in the
course of sickness among subjects in the population can also be
explained by covariates on transition intensities. MSMs, in partic-
ular, can show how various variables effect different transitions,
which is impossible to do with other models like the TDCM. In
reality, the risk of mortality in individuals who have undergone
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Volume 8 Issue 14 -2022 Mini Review
different therapy is unlikely to be the same. Furthermore, prognos-
tic markers linked to the risk of mortality may vary based on the
treatment received, for example. There is currently a substantial
amount of research accessible on the analysis of MSMs [27-31].
8. Some Recurrent and Emerging Issues in Biostatistics
In terms of both the continued improvement of traditional ap-
proaches and the introduction of new techniques to meet new
issues, modern biostatistics faces a variety of obstacles. We next
turn our focus to a number of emergent topics that biostatisticians
should investigate further, including bioinformatics, spatial statis-
tics, neural networks, and functional data analysis, as well as big
data analysis.
8.1. Statistical methods in bioinformatics
A very rapidly emerging influence on biostatistics is the on-going
revolution in molecular biology. Molecular biology is now evolv-
ing towards information science, and is energizing as a dynamic
new discipline of computational biology, sometimes referred to as
bio-informatics. Bio-informatics merges recent advances in mo-
lecular biology and genetics with advanced statistics and computer
science. The goal is increased understanding of the complex web
of interactions linking the individual components of a living cell
to the integrated behaviour of the entire organism. The availability
of large molecular databases and the decoding of the human ge-
nome may allow a scientist to plan an experiment and immediately
obtain the relevant data from the available databases. This is an
area in which statistical scientists can make very important con-
tributions. Several biostatistics departments (mainly in the U.S.)
have already been renamed as “Biostatistics and Bioinformatics”
[32-33].
8.2. Spatial statistical methods in health studies
In numerous types of public health and epidemiological studies,
the investigation of the geographical distribution of illness inci-
dence and its link to possible risk factors plays an essential role.
Geographic epidemiology is the overall term for this field, and
there are four major statistical areas of interest: (a) Given "noisy"
observed data on illness rates, disease mapping tries to construct a
map of the genuine underlying geographical distribution of disease
incidence.
(b) Ecological studies look for correlations between sickness inci-
dence and potential risk factors in groups rather than individuals,
with groups frequently defined by geographic location. Such stud-
ies are helpful in discovering the cause of sickness and may con-
tribute in suggesting future research paths as well as prospective
preventative strategies. (c) Disease clustering research focuses on
finding geographical locations with a considerably higher risk of
disease, or evaluating the evidence of heightened risk near poten-
tial sources of hazard. The exploration of control measures when
the aetiology of observed clustering has been established, or the
targeting of follow-up studies to determine explanations for ob-
served clustering in disease incidence. (d) Environmental assess-
ment and monitoring is concerned with determining the geograph-
ical distribution of health-related environmental elements and
exposure to them in order to develop appropriate controls or take
preventative action. Given the scope and relevance of the issues
raised by spatial epidemiology, it's no surprise that there's been a
lot of interest in this field in recent years [34-36].
8.3. Neural networks in medicine
Many researchers have been drawn to neural networks (NN) tech-
niques in medicine, and these approaches have been used in a
variety of biomedical applications, including diagnostic systems,
biochemical analysis, image analysis, and drug discovery. Neural
networks, which mimic the behaviour of human neuron networks,
have the potential to be beneficial in a wide range of applications.
NNs, unlike humans, are not influenced by factors like as weari-
ness, working environment, or emotional state. NNs are frequently
employed in diagnostic systems, for the diagnosis of cancer and
heart issues, and for the analysis of many types of medical pic-
tures (such as tumour detection in ultrasonograms, classification
of chest x-rays, and tissue and vascular classification in magnet-
ic resonance imaging). Many researchers are interested in neural
networks (NN) approaches in medicine, and these NNs are being
used experimentally to model the human cardiovascular system:
diagnosis can be achieved by building a model of an individual's
cardiovascular system and comparing it to real-time physiological
measurements taken from that patient. NNs are also employed in
the research and development of cancer and AIDS medications.
In addition to classical and current statistical approaches, neural
networks are increasingly being viewed as an extension to generic
statistical methodology [37-39].
8.4. Functional data analysis and medicine
Because of technology advancements in recent years, many sci-
entific domains including applied statistics are increasingly mea-
suring and recording continuous (i.e., functional) data. Many cur-
rent devices, for example, allow biomedical researchers to obtain
functional data samples (mainly as curves, though also as images).
Because functional data is displayed as a curve, the curve is a good
starting point for functional data analysis. Functional data often in-
volves a large number of repeated measurements per subject, and
these measurements are typically captured at the same (generally
similarly spaced) time intervals and with the same high sampling
rate for all participants. The derivatives of these curves, as well
as the positions and values of extremes, are occasionally of in-
terest. In endocrinology, for example, investigations of hormone
levels after various pharmacological dosages; or in neuroscience,
for example, studies to estimate the firing rate of a population of
neurons, where the unit of research is each individual neuron's fir-
ing curve. Another example is the study of growth curves in which
many characteristics of growth, such as height and lung function,
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Volume 8 Issue 14 -2022 Mini Review
are studied [40]. The goals of functional data analysis are generally
exploratory in nature, with the goal of representing and display-
ing data in order to highlight noteworthy qualities that may then
be used as input for further research. Other goals might include
estimating individual curves from noisy data, characterisation of
homogeneity and patterns of variability across curves, and evalua-
tion of the correlations between curve forms and variables. Despite
substantial recent advances in functional data analysis, the statisti-
cal community has a huge problem in developing new tools to deal
with functional data. Aside from the books already mentioned, the
special issue on functional data, which is set to appear in the jour-
nal Computational Statistics and Data Analysis soon (2007), may
be an excellent place to start thinking about new areas of statistical
study and prospective applications.
9. New Statistical Methods which are Likely to Play a
Key Role in Biomedical Research Over Coming Years
The following new statistical methods are likely to play a key role
in biomedical research over coming years: (i) bootstrap (another
computer-intensive methods); (ii) Bayesian methods); (iii) gen-
eralized additive models;(iv) classification and regression trees
(CART); (v) models for longitudinal data (general estimating equa-
tions); and (vi) models for hierarchical data, (vii) big data analysis
[41]. Modern health research involves increasingly sophisticated
statistical tools and computerized systems for data management
and analysis. During the past few years’ tremendous amount of
software has been made available to support statistical computing
requirements for biomedical research. Bio-statisticians have to be
extremely familiar with various statistical software packages such
as STATA, SAS, SPSS,R etc.
The traditional component of biomedical courses will probably
focus on areas of mathematical statistics including probability
theory, inference, re-sampling methods (e.g. bootstrap), linear re-
gression, analysis of variance, generalized linear models, survival
analysis (including multi-state models), nonparametric methods,
and data analysis. In addition, new methodologies like spatial sta-
tistics, neural networks, smoothing regression methods (such as
generalized additive models) and operations research are strongly
recommended. The decision technologies, tools and theories of
operations research and management Sciences have long been ap-
plied to a wide range of issues and problems within health care.
10. Conclusion
Biostatistics is a fundamental scientific field in public health,
health services, and biomedical research. With the rise of medi-
cal sciences and public health-oriented research over the last few
decades, biostatistics has grown more quantitative, stochastic, and
evidence-based. Emerging fields including machine learning, clin-
ical epidemiology, molecular biology, genomics, and pharmaco-
kinetics have all led to a growing reliance on biostatistics in med-
ical and health sciences. Medicine is a science in which chance
is a significant factor. Statistics as a science may help quantify
the influence of chance, but statistics as an art can help individual
doctors make appropriate diagnostic, prognostic, and therapeutic
decisions. The use of Biostatistical methods to address issues in
clinical trials, survival analysis, Data modelling using General-
ized linear models, genetics, ecology and machine learning etc are
gaining much popularity in the present era of in epidemiological
biomedical research.
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Bio-Statistics newer advances, Scope & Challenges in Bio-Medical Research

  • 1. Annals of Clinical and Medical Case Reports Mini Review ISSN 2639-8109 Volume 8 Bio-Statistics Newer Advances, Scope & Challenges in Bio-Medical Research Murthy NS1 , Kunnavil R2 and Shivaraj NS3 1 Former Research Director, DRP and Professor and Research Coordinator, M.S. Ramaiah Medical College & Hospitals (MSRMC), Bangalore, India. 2 Lecturer in Biostatistics, National Institute of Unani Medicine, Bangalore, India 3 Assistant professor Statistics, Department of Community Medicine, M.S. Ramaiah Medical College & Hospitals (MSRMC), Banga- lore, India * Corresponding author: Radhika Kunnavil. Lecturer in Biostatistics, National Institute of Unani Medicine, Bangalore- 560091, India, Tel: 7829606040, E-mail: radhik121@gmail.com Received: 25 Feb 2022 Accepted: 09 Mar 2022 Published: 14 Mar 2022 J Short Name: ACMCR Copyright: ©2022 Kunnavil R. This is an open access article dis- tributed under the terms of the Creative Commons Attri- bution License, which permits unrestricted use, distribu- tion, and build upon your work non-commercially. Citation: Kunnavil R, Bio-Statistics Newer Advances, Scope & Challenges in Bio-Medical Research. Ann Clin Med Case Rep. 2022; V8(14): 1-7 Keywords: Biostatistics; Bio-medical research; Scope; Appli- cations; challenges http://www.acmcasereport.com/ 1 1. Abstract Biostatistics also known as biometry which means ‘measurement of life’is a branch of applied statistics which deals with collection, compilation, analysis and interpretation of data related to biomed- ical sciences. It provides a key to better understanding of the med- ical discipline. Biological data are always subjected to variation and are affected by various environmental, social and genetic fac- tors etc. Biostatistics proves a tool for analysing the data taking into account the variability and to elicit meaningful conclusion in research. In this era of evidence-based medicine. Nowadays, the discipline of biostatistics acts as a basic scientific entity of public health, health services and biomedical research. Biostatistics has evolved as a branch of science in biomedical research that uses a combination of statistics, probability, mathematics and computing to resolve perplexing questions mathematically. Because research questions in biology and medicine are diverse, biostatistics has expanded its domain to include any complex quantitative model to answer research questions. Biostatistics has reach in wide spec- trum of biomedical domains. From drug development in a labo- ratory to development of various disease control and prevention measures at community level and a lot more. The important aspect for biostatistics is that it helps in valid clinical decision making by elucidating and quantifying the contribution of chance. Overtime this field has expanded its wings and now it is widely used across many systems of medicine including Ayurveda, Unani etc. The computer programmes and advent of newer methods has increased its scope and applications. This paper aims to through light on the newer advances in biostatistics. This paper explores the newer methods, scope & few challenges in Bio-Medical Research. 2. Introduction Bio-statistics has pivotal role in the development of medical and biological sciences as well as in the development of various dis- ease control and prevention measures. Nowadays, the discipline of biostatistics acts as a basic scientific entity of public health, health services and biomedical research. Over the last few de- cades, bio-statistics have become more quantitative, stochastic, evidenced based with the growth of medical sciences and public health-oriented research. Emerging disciplines such as Machine learning, Clinical Epidemiology, Molecular Biology, Genomics and Pharmacokinetics have all contributed to making medical and health sciences depend more and more on Biostatistics. The present write-up focusses on role and use of bio-statistics in the epidemiology, bio-medical research as well as some to touch upon newer methods, scope & few challenges in Bio-Medical Research. 3. Bio-Statistics as a Stream Over the last few decades, the development of statistical methods has expanded. Statistics applied to medical research – biostatis- tics – may now be regarded a subject in its own right, research in medicine and public health has been both a benefactor and a
  • 2. http://www.acmcasereport.com/ 2 Volume 8 Issue 14 -2022 Mini Review source of new difficulties as a result of this new technique. In re- ality, biostatistics has evolved into a distinct field of study that solves issues in the biological sciences by combining statistics, probability, mathematics, and computing. Biostatistics has broad- ened its area to encompass any quantitative, not just statistical, model that may be used to answer these issues, due to the diversity of research questions in biology and medicine. Biostatistics is a field that aims to provide information. Consequently, biostatistics draws quantitative methods from fields including statistics, oper- ations-research, economics, and mathematics in general; and it is applied to research questions in fields such as epidemiology, nutri- tion, environmental health, and health services research, genomics and population genetics, clinical medicine, and ecology. The significance of biostatistics and biostatisticians in medical re- search has long been acknowledged by the biomedical communi- ty, and statistics in medicine may now be regarded a successful paradigm for the incorporation of statistics into scientific practice. The relevance of biostatisticians in the biomedical profession may be seen in the fact that they are frequently asked to contribute as advisers on renowned committees and journals. Furthermore, spe- cific statistical publications such as Biostatistics, Biometrics, Bio- metrika, and many other biostatistics-related journals are held in high esteem [1-2]. 4. Types of Research Investigations in Bio-Medical Field Quality biomedical research is based on a foundation of careful study design. Over the last several decades, newer and innovative concepts and statistical methods for the design and analysis of data in biological studies have been established and are being used. De- sign of studies such as case-control studies, cohort studies, clinical trials, and survival studies has been the center of development. The application of epidemiologic ideas and techniques to the design, conduct, and analysis of clinical trials is a major development, with comprehensive applications described in the following para- graphs. Observational and experimental research studies are the two categories of scientific research studies in biomedical field. Selection of subjects on whom measurements are made is one of the most essential problems that occur during the formulation of statistical methods of research [3-5]. 5. Why is Statistics Necessary in Bio-Medical Field? Without appropriate inferences, empirical research in any field is incomplete, and biomedical research is no exception. Both the design of diverse biomedical research investigations and the eval- uation of outcomes need the use of proper statistical tools. Biosta- tistics has now become a crucial component in several research domains as a result of expansion of quantitative approaches with in biomedical sciences (bio-chemical, physiological, clinical pa- rameters, or evidence-based medicine). Medicine is a science in which chance plays an important role. Statistics as a science aid in quantifying the role of chance, whereas statistics as an art aids in- dividual clinicians in making accurate diagnostic, prognostic, and therapeutic judgments. It also aids health programme administra- tors and policymakers in the planning, monitoring, and evaluation of public health efforts. A health indicator can be used to describe one or more aspects of an individual's or population's wellbeing (quality, quantity, and time), and also to define public health prob- lems at a specific moment in time, to indicate changes in levels of a population's or individual's health over time, to define distinctions in population health, and to assess the extent to which a program's objectives are being met. Similarly, validity metrics including sen- sitivity, specificity, positive and negative predictive value are used to evaluate the quality and usefulness of a diagnostic test or to determine the efficiency of a marker in disease diagnosis [3]. 5.1. Epidemiology and Biostatistics Epidemiology is the branch that studies diseases occurrence and its reasons in different groups of people. Epidemiological data is used to design and evaluate disease prevention initiatives, as well as to guide the treatment of patients who already developed disease. Biostatistics and epidemiology have historically had such a signif- icant link. The early public health experts were doctors basically keen to understand the path wherein ailments eventuate in popula- tions, their causes, as well as their interrelations with various med- ical and non-medical aspects. These innovators' challenges includ- ed not just the study of epidemics and non-communicable diseases such as the connection between smoking and lung cancer, but also the evaluation of therapies. Many had strong analytical reasoning abilities and were well-versed in statistical methods. Then, begin- ning in the 1930s, epidemiology began focusing upon that study of chronic diseases. The same prospective research strategies that had been so clearly appropriate in the study of infectious diseases became untenable. And it was statisticians, particularly Cornfield and Mantel, who provided a rationale for clarify case-control in- ference. With concerns about bias related to possible confounding factors, biostatisticians have become more interested in growing on the prerequisites for valid inference. They also began searching at other areas of epidemiological research, including models for eval- uating the effects of potential disease risk factors, such as dose re- sponse models. These effects are quantified employing probabilis- tic notions such as the odds ratio or relative risk, which can be es- timated appropriately based on the type of study (case-con- trol, cross sectional, or cohort) used for each research proj- ect. The large number of statistical methods required in epidemi- ology has led to the publication of numerous books on statisti- cal applications in epidemiological contexts [6-9]. 5.2. Clinical trials and biostatistics Clinical studies are a crucial component of medical research. Sci- entific advance can lead to better ways of diagnosing, detecting, and treating diseases and medical conditions as a consequence of these clinical studies. Clinical trials are research studies which use
  • 3. http://www.acmcasereport.com/ 3 Volume 8 Issue 14 -2022 Mini Review human subjects to evaluate novel therapies or drug combinations, modern surgical or radiotherapy approaches, or new procedures in order to improve illness diagnosis or quality of life for patients. Most hospitals now participate in drug testing, which are only started once laboratory investigations show that a new treatment or technique is safe and also has the potential to be more efficient than existing options. Statistics have become increasingly import- ant in the field of pharmaceutical development in recent years. From planning through conduct and interim analysis to final anal- ysis and reporting, statistics is essential at each and every stage of a clinical trial [10-11]. The statistician is typically in responsi- ble for formulating randomization schedules, advising on sample size, establishing framework for deciding treatment differences, and evaluating response rates. In most instances, the statisticians will also act as a liaison with the Independent Data Monitoring Committee. Several novel and recurring challenges in the drug development process require special attention. Ongoing develop- ment of statistical methods for handling subgroups in the design and analysis of clinical trials; alternatives to "intention-to-treat" analysis in the presence of noncompliance in randomized clinical trials; methodologies to address the multiplicities resulting from a variety of sources, methods to assure data integrity etc all of which are inherent in the drug development process. These con- cerns continue to be a source of contention for statisticians work- ing in the pharmaceutical industry across the world. Furthermore, the engagement of statisticians from all backgrounds continues to enrich the profession and contribute to social health improve- ments. Biostatisticians' significant methodological contributions to clinical trials research has led to the development of a new journal, Pharmaceutical Statistics, which was just published in 2002 and is already placed in the JCR ranking for Statistics and Probability. 6. Advanced Statistical Areas of interest in Bio-Medical Field In addition to routine descriptive and inferential statistics, gen- eralised linear models, survival analysis, and Bayesian methods etc have already had a significant impact on the medical statistics in recent years (in diagnostic, epidemiological and clinical trials contexts). Regression analysis or linear discriminant analysis are statistical approaches used in the biomedical profession to predict a dependent variable using additional independent variables/ fea- tures or to divide persons into two or more classes of objects or events based on illness status. The approaches outlined above have aided in the reduction of dimensionality as well as the classifying of people as sick or non-diseased [7-13]. 7. Modeling-Approach in Epidemiological Research/ Bio-Medical Filed - Generalized Linear Models Modeling of health and disease process has been a complex phe- nomenon. Several models have been employed for the analysis and interpretation of data in the biological field. In the forgoing sections, it is proposed to describe three different types of general linear models which have been extensively employed as multi- variate procedures in bio-medical field viz. (i) Age-period cohort models, (ii) Logistic regression model and (iii) Survival analysis. 7.1. Importance of time-related analysis Cancer incidence/mortality rates from population-based registries (which gather data on all cancer cases in specified areas) give in- formation on regional and temporal variation in cancer risk by personal variables including age, sex, and racial or ethnic group- ings. "Time," the third element of an epidemiological description, provides information on geographic areas and serves as the foun- dation for determining how effective cancer-prevention methods are. Changes in cancer pattern over time are of critical importance in cancer control efforts. Age at risk, calendar year, and birth co- hort impact are the most often evaluated time-related confounders. The trend analysis helps to understand the question such as how cancer risk has been changing, why and what is likely to happen in future. Cancer trend analysis is important information for the public health and health care planning. Trend analysis reveals in- formation on the disease's aetiology and the significant variance in its prevalence across different geographic areas. Cancer incidence/ mortality trends can also be used to forecast future cancer patterns, which can help shape future public health policy. The suitable tools for assessing trends in cancer incidence/mortality data include data modelling by age, birth cohort, and calendar time period. "Age-pe- riod-cohort (ACP) models" are the name for these models. These models are based on regression models with a Poisson distribu- tion [14].Using the data from the Indian Population Based Cancer Registries for the past twenty-five years, the aforesaid modelling approach was used to predict the changes in the incidence of com- mon malignancies. Some malignancies, such as breast, ovarian, corpus, and uterus, were found to be rising at a rate of around 1-2 percent every year, according to the research, and the similar trend was seen in women of a younger age range [15-18]. 7.2. Modelling of the data in case of binary outcome event When the dependent variable (outcome variable) is binary in na- ture, such as whether an event occurs or not, taking values of unity or zero, the assumption required for fitting a multiple linear re- gression model of the type Y= α +Σk i=1 βXi is violated because it is unreasonable to assume that error distribution is normal. Mul- tiple logistic regression analysis (LR) is used as a multivariate approach to discover the independent predictors of the outcome variable instead of multiple linear regression analysis. The key difference between LR and multiple linear regression models is that instead of utilising the dependent variable as is, we utilise a model based on the dependent variable's logit transformation to meet the required assumptions. As a result, in the LR model, we forecast the proportion of subjects (P) who have a specific charac- teristic, or, alternatively, the probability of having characteristics for any combination of explanatory factors [8,19,20]. A dichoto- mous outcome variable is linked to a set of "k" known or suspected
  • 4. http://www.acmcasereport.com/ 4 Volume 8 Issue 14 -2022 Mini Review causes (regression variables), as well as probable confounding and effect modification variables, in this model. Covariates or explan- atory variables are a collection of k regression variables or risk factors. The approach of maximum likelihood estimation is used to estimate the unknown parameters in the model, α, and βi . In most cases, the likelihood inference is preceded by the fitting of a hierarchy of models, each of which contains the last variable. The likelihood ratio test or a test based on Wald statistics are used to test the hypothesis. This modelling approach was used to find independent risk variables linked to illness or a negative outcome event. The logistic regression approach was used in research to look at the impact of maternal and perinatal outcomes in different degrees of anaemia. Mild anaemia had the best maternal and peri- natal outcomes, according to the research. Low birth weight kids, induction rates, surgical deliveries, and protracted labour have all been linked to severe anaemia [21]. 7.3. Studies on survival analysis Understanding the link between time and the occurrence of vital and health-related events requires the study of lifetime data. In the biomedical area, time-to-event data is regularly encountered for study. This type of study is known as "survival analysis." The time passed between a subject's enrollment into the research and the occurrence of an event that is related to treatment is the outcome variable in follow-up/survival studies. The outcome variable has been dubbed survival time, and the event of interest (the onset of a disease) has been dubbed failure. In oncology, for example, the focus is usually on the patient's chance of survival after a surgical procedure. Issues of censoring and truncation hamper the analysis of this sort of survival trial. The analysis of lifetime data is important in understanding the re- lationship between time and occurrence of vital and health related events. Time-to-event data is frequently encountered for analysis in bio-medical field. Such analysis is called as "survival analysis". In follow-up/ survival studies, the outcome variable is the time elapsed between the entry of a subject into the study and the oc- currence of an event is related to treatment. The event of interest (development of a disease, death) has been referred to failure and the outcome variable as the survival time. In oncology, for exam- ple, interest typically centers on the patient’s time of survival fol- lowing a surgical intervention. The analysis of this type of survival experiment is complicated by issues of censoring and truncation. Censoring occurs when we do not fully observe the patient’s sur- vival, due to death unrelated to the cancer under study, or dis- appearance from the study for some reason. The other factor is truncation, which basically occurs when some patients can’t be observed for some reasons related to the survival itself. A common example of this is in HIV/AIDS studies of the incubation period (i.e., time from infection to disease). The follow-up starts when the HIV virus is detected and the moment of infection is retro- spectively ascertained. Several survival parametric models such as Exponential and Weibull distributions were introduced to model the survival experience/follow-up data analysis of homogeneous populations incorporating the censoring schemes. The distribution of survival times must be known to apply these models. However, when the distribution of survival is not known, the non-parametric method of Kaplan-Meier curve developed in 1959 has been a well- known estimator of the survival function, and it is extensively used in epidemiological and clinical research [20-24]. In order to take into account diversity of situations, which were encountered in practice, Cox in 1972 developed a modelling pro- cedure termed as Cox-proportional hazards model under a very rigorous theoretical backup. The classical proportional hazards model of Cox (1972) is also widely used whenever the goal is to study how covariates affect survival. This model is an important tool in the follow-up/survival studies for modelling the effect of risk factors/prognostic factors when the outcome of interest occurs with time. In the model, the hazard for an individual is a part of the product of a common baseline hazard and a function of set of risk factors. By applying the above modelling procedure, the in- dependent risk factors associated with the development of precan- cerous lesions of cancer of cervix was evaluated [25]. Similarly, in another study the treatment effectiveness for curing of a gastro intestinal bleeding was evaluated which employed an experimen- tal design [26]. However, when the assumption of proportionality does not satisfy, then a classical approach for the analysis of data of this type is the time-dependent Cox regression model (TDCM). Advantages of Cox’s regression model include its easy interpret- ability and its availability in the majority of statistical packages. 7.4. New issues in survival analysis When survival is the ultimate result yet intermediate phases are discovered, a generalisation of the survival process occurs. In this case, a series of occurrences is witnessed, resulting in many observations per person. Intermediate stages might be based on categorical time-dependent factors like transplantation, clinical symptoms (e.g., bleeding episodes), or a complication during the disease (e.g., metastases), or biological markers (like CD4T-lym- phocyte levels). Multi-state models (MSMs) were accessible in the 1990s, allowing for a better grasp of the disease process and a bet- ter comprehension of how the time dependent covariate impacts the illness's evolution. Compared to Cox's regression model, these contemporary models offer significant advantages. They provide a better understanding of the illness process by indicating the risk of moving from one condition to another (transition intensities), as well as a variety of additional data, such as the average time spent in each state and survival rates for each stage. Differences in the course of sickness among subjects in the population can also be explained by covariates on transition intensities. MSMs, in partic- ular, can show how various variables effect different transitions, which is impossible to do with other models like the TDCM. In reality, the risk of mortality in individuals who have undergone
  • 5. http://www.acmcasereport.com/ 5 Volume 8 Issue 14 -2022 Mini Review different therapy is unlikely to be the same. Furthermore, prognos- tic markers linked to the risk of mortality may vary based on the treatment received, for example. There is currently a substantial amount of research accessible on the analysis of MSMs [27-31]. 8. Some Recurrent and Emerging Issues in Biostatistics In terms of both the continued improvement of traditional ap- proaches and the introduction of new techniques to meet new issues, modern biostatistics faces a variety of obstacles. We next turn our focus to a number of emergent topics that biostatisticians should investigate further, including bioinformatics, spatial statis- tics, neural networks, and functional data analysis, as well as big data analysis. 8.1. Statistical methods in bioinformatics A very rapidly emerging influence on biostatistics is the on-going revolution in molecular biology. Molecular biology is now evolv- ing towards information science, and is energizing as a dynamic new discipline of computational biology, sometimes referred to as bio-informatics. Bio-informatics merges recent advances in mo- lecular biology and genetics with advanced statistics and computer science. The goal is increased understanding of the complex web of interactions linking the individual components of a living cell to the integrated behaviour of the entire organism. The availability of large molecular databases and the decoding of the human ge- nome may allow a scientist to plan an experiment and immediately obtain the relevant data from the available databases. This is an area in which statistical scientists can make very important con- tributions. Several biostatistics departments (mainly in the U.S.) have already been renamed as “Biostatistics and Bioinformatics” [32-33]. 8.2. Spatial statistical methods in health studies In numerous types of public health and epidemiological studies, the investigation of the geographical distribution of illness inci- dence and its link to possible risk factors plays an essential role. Geographic epidemiology is the overall term for this field, and there are four major statistical areas of interest: (a) Given "noisy" observed data on illness rates, disease mapping tries to construct a map of the genuine underlying geographical distribution of disease incidence. (b) Ecological studies look for correlations between sickness inci- dence and potential risk factors in groups rather than individuals, with groups frequently defined by geographic location. Such stud- ies are helpful in discovering the cause of sickness and may con- tribute in suggesting future research paths as well as prospective preventative strategies. (c) Disease clustering research focuses on finding geographical locations with a considerably higher risk of disease, or evaluating the evidence of heightened risk near poten- tial sources of hazard. The exploration of control measures when the aetiology of observed clustering has been established, or the targeting of follow-up studies to determine explanations for ob- served clustering in disease incidence. (d) Environmental assess- ment and monitoring is concerned with determining the geograph- ical distribution of health-related environmental elements and exposure to them in order to develop appropriate controls or take preventative action. Given the scope and relevance of the issues raised by spatial epidemiology, it's no surprise that there's been a lot of interest in this field in recent years [34-36]. 8.3. Neural networks in medicine Many researchers have been drawn to neural networks (NN) tech- niques in medicine, and these approaches have been used in a variety of biomedical applications, including diagnostic systems, biochemical analysis, image analysis, and drug discovery. Neural networks, which mimic the behaviour of human neuron networks, have the potential to be beneficial in a wide range of applications. NNs, unlike humans, are not influenced by factors like as weari- ness, working environment, or emotional state. NNs are frequently employed in diagnostic systems, for the diagnosis of cancer and heart issues, and for the analysis of many types of medical pic- tures (such as tumour detection in ultrasonograms, classification of chest x-rays, and tissue and vascular classification in magnet- ic resonance imaging). Many researchers are interested in neural networks (NN) approaches in medicine, and these NNs are being used experimentally to model the human cardiovascular system: diagnosis can be achieved by building a model of an individual's cardiovascular system and comparing it to real-time physiological measurements taken from that patient. NNs are also employed in the research and development of cancer and AIDS medications. In addition to classical and current statistical approaches, neural networks are increasingly being viewed as an extension to generic statistical methodology [37-39]. 8.4. Functional data analysis and medicine Because of technology advancements in recent years, many sci- entific domains including applied statistics are increasingly mea- suring and recording continuous (i.e., functional) data. Many cur- rent devices, for example, allow biomedical researchers to obtain functional data samples (mainly as curves, though also as images). Because functional data is displayed as a curve, the curve is a good starting point for functional data analysis. Functional data often in- volves a large number of repeated measurements per subject, and these measurements are typically captured at the same (generally similarly spaced) time intervals and with the same high sampling rate for all participants. The derivatives of these curves, as well as the positions and values of extremes, are occasionally of in- terest. In endocrinology, for example, investigations of hormone levels after various pharmacological dosages; or in neuroscience, for example, studies to estimate the firing rate of a population of neurons, where the unit of research is each individual neuron's fir- ing curve. Another example is the study of growth curves in which many characteristics of growth, such as height and lung function,
  • 6. http://www.acmcasereport.com/ 6 Volume 8 Issue 14 -2022 Mini Review are studied [40]. The goals of functional data analysis are generally exploratory in nature, with the goal of representing and display- ing data in order to highlight noteworthy qualities that may then be used as input for further research. Other goals might include estimating individual curves from noisy data, characterisation of homogeneity and patterns of variability across curves, and evalua- tion of the correlations between curve forms and variables. Despite substantial recent advances in functional data analysis, the statisti- cal community has a huge problem in developing new tools to deal with functional data. Aside from the books already mentioned, the special issue on functional data, which is set to appear in the jour- nal Computational Statistics and Data Analysis soon (2007), may be an excellent place to start thinking about new areas of statistical study and prospective applications. 9. New Statistical Methods which are Likely to Play a Key Role in Biomedical Research Over Coming Years The following new statistical methods are likely to play a key role in biomedical research over coming years: (i) bootstrap (another computer-intensive methods); (ii) Bayesian methods); (iii) gen- eralized additive models;(iv) classification and regression trees (CART); (v) models for longitudinal data (general estimating equa- tions); and (vi) models for hierarchical data, (vii) big data analysis [41]. Modern health research involves increasingly sophisticated statistical tools and computerized systems for data management and analysis. During the past few years’ tremendous amount of software has been made available to support statistical computing requirements for biomedical research. Bio-statisticians have to be extremely familiar with various statistical software packages such as STATA, SAS, SPSS,R etc. The traditional component of biomedical courses will probably focus on areas of mathematical statistics including probability theory, inference, re-sampling methods (e.g. bootstrap), linear re- gression, analysis of variance, generalized linear models, survival analysis (including multi-state models), nonparametric methods, and data analysis. In addition, new methodologies like spatial sta- tistics, neural networks, smoothing regression methods (such as generalized additive models) and operations research are strongly recommended. The decision technologies, tools and theories of operations research and management Sciences have long been ap- plied to a wide range of issues and problems within health care. 10. Conclusion Biostatistics is a fundamental scientific field in public health, health services, and biomedical research. With the rise of medi- cal sciences and public health-oriented research over the last few decades, biostatistics has grown more quantitative, stochastic, and evidence-based. Emerging fields including machine learning, clin- ical epidemiology, molecular biology, genomics, and pharmaco- kinetics have all led to a growing reliance on biostatistics in med- ical and health sciences. Medicine is a science in which chance is a significant factor. Statistics as a science may help quantify the influence of chance, but statistics as an art can help individual doctors make appropriate diagnostic, prognostic, and therapeutic decisions. The use of Biostatistical methods to address issues in clinical trials, survival analysis, Data modelling using General- ized linear models, genetics, ecology and machine learning etc are gaining much popularity in the present era of in epidemiological biomedical research. References 1. Altman DG and Goodman S. 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