In reading the Holmes et al paper “Fulfilling the Promise of Personalized Medicine? Systematic Review and Field Synopsis of Pharmacogenetic Studies” I would like you to think about some questions:
- The paper discusses the “excitement” surrounding pharamacogenomics, but points out that a large volume of these papers are reviews, rather than primary research articles. Why is this a problem? Why do you think it is happening. What reasons do the authors give?
- What would make a clinical study “A primary pharmacogenetic” study?
- On page 12, the autors state “As more reliable information begins to emerge on alleles influencing drug response from larger, better designed whole genome and candidate gene studies, focus will need to shift to the critical evaluation of the predictive performance of genetic tests in clinical practice, including studies of cost-effectiveness.” What does this mean? What are the authors expecting to happen in the field? Why is “more reliable information” emerging?
- Pick any of the authors “Recommendations for Future Research in Pharmacogenetics” and explain what it means, using examples.
Gillespie Lab 
I believe that scientists write reviews on previous research because they deem the research topics relevant to modern medicine and are comfortable dealing with the central dogmas of their field; besides, it’s easier to write about something that been proven rather than attempting to start a new study on something both new and relevant. Valid and useful experiments that “figure out something new” are hard to come by, but if you don’t try then there will be no progress.
A clinical study is a primary pharmacogenetic study when it describes direct interactions between a gene or drug and its effects. The authors of this study want to see more studies evaluating and predicting the future usefulness and practicality of pharmacogenomics, as well as further testing on the ability to actually create personalized medicine on a large-scale that is accessible to multiple populations.
The authors specifically recommended conducting research using individuals from varied backgrounds and ethnicities. For example, in June 2007 there was research into a lung cancer drug that worked better in people of Japanese decent versus Caucasian individuals because of the genetic differences between the ethnic groups.
“Fulfilling the Promise of Personalized Medicine” is a scholarly journal that talks about the problems in the field of pharmacogenetic studies. This research study generated an analysis by filtering through various written materials, yet found many of them to be reviews rather than research articles. This poses an enormous problem because by writing reviews of what has been done, nothing new is discovered. Instead we are simply recycling the same material over and over. Often enough we become more acquainted with particular groups of genes over other. A possible explanation to this problem could be that researchers feel the need to analyze more in depth about a particular gene that causes a problem, such as cancer or cardiovascular disease and therefore choose to write about the results of a previously conducted research experiment. Or it could be that they are just lazy and despise the idea of conducting a research project of their own. One reason the authors give is that researchers have thousands of hypotheses but can’t always identify which are the ones that are worthy of being tested.
Clinical studies that are considered “primary pharmacogenetic studies” are the ones that explicitly state the purpose and aim of the study within the research or the abstract. In addition, the outcome of a research can also help to determine the type of study. If the actual outcome matches with the aim of the study, then it is primary. However, if the outcome of the research does not answer the aim of the research, then the study would be considered secondary. An example would be testing for side effects of a certain drug.
Although not every research study can be useful in explaining gene behavior toward a particular drug, as more of these studies are conducted, they will trigger more information to be released. However, there is a definite need to study genes that are less familiar to our knowledge. Perhaps in the near future we will acquire more information about these rare genes that cause problems. Ultimately, the result of these studies will ensure more reliable information to emerge because we will begin to see a broader scope of studies and discoveries.
I consider this article to be scholarly because it presents some of the key problems in pharmacogenetic studies and suggest possible solutions. One of the recommendations was that studies should “be appropriately powered.” In other words, studies need to incorporate gene samples of different race and genetic backgrounds and not only focus on testing the gene samples of European descent. Overall I feel that although the reading is tedious, the article has helped me tremendously in recognizing some of the current issues of pharmacogenetic study.
In this paper, the idea that there are problems with the research in the field of pharmacogenomics is discussed. Personally, I found this paper hard to read due to the nature that it is a review or secondary literature, rather than a primary piece of research. This field’s research is often discussed through review articles for a multitude of reasons. The first being that’s scientists may find it easier to use other people’s data and make their own analyses from it. The second reason would be that scientists may not want to publish their own work if they receive results that are not expected. In my opinion though, publishing results that show unexpected or adverse effects are just as important as receiving expected results. The last reason that scientists may rely more on review papers rather than a primary paper would be that they are going in circles. In the paper, it was mentioned that only certain categories such as cancer or cardiovascular related genes were being studied. Scientists may not know where to go outside of these gene groups that already have data published and instead would prefer to further analyze the results. I think that in order for the problems present currently in the field of pharmacogenics to be fixed, more primary research does need to occur. A clinical study could be made into a primary pharmacogentic study by doing actual research on a particular gene and presenting that data.
In the discussion section of the paper, the authors begin to get at the idea that changes do need to be made to the field, which are expressed in a list at the end of the paper. Some of the problems that I found within this paper were the selectivity of the participants, the sample size, the variety of categories of genes being studied and the concept of exceptions. As mentioned in the “Recommendations for Future Research in Pharmacokinetics” section, the authors make the point that participants have to have more of a mixed heritage other than European or American. The world that we live in today is not made up of just these races. With the different races come differences in genes also so it would be beneficial to study more than just this select group of individuals. Another problem would be that the sample size for each category of genes (somatic, kinetic, dynamic) were not around the same number. Although this is a review article, I almost wished that they had focused on one of these sets of groups rather than all three because it felt a little overwhelming. The last problem that I found while reading this paper was what made me realize that there are problems with the research in this field; exceptions. In the methodology section, they mention in various places a set of descriptions on how things were grouped but then at the end would have an exception. Although things aren’t always set in stone, having all these exceptions shined out to me as there being problems in the way the research was being conducted.
Even though the style of this paper was confusing at times, I did find the topic of exposing the field for its problems interesting and refreshing. Scientists normally don’t want to expose their faults, especially ten years worth. I also enjoyed how this paper exposed us to the clinical structure. I have done research in the past and have found paragraph structured abstracts hard to read and write. This structure definitely accomplished the goal of what an abstract should do; summarize the paper in layman’s terms.
Pharmacogenomics field of study is not able to thrive because of some drawbacks related to approach taken towards developing a research process.
Large volume of papers are springing up as reviews rather than the primary research which is creating a problem in the pharmacogenomics field of study because the original research has not been able to publish articles relevant to the field it comprises of. Inefficacies of the experiments performed are nurturing major concerns toward this particular field of pharmacogenomics and some of the intriguing factors include the sample size, collection of data from large population to reflect on adverse and intended effect of the particular drug intake.
Since article states that “pharmacogenetic research centres mainly in cancer, cardiovascular, neurological/psychiatric disease with most studies being set in Europe and North America, presumably mainly among subjects of European ancestry.” This statement sheds light on the area we might need to improve before proceeding to further the experiment. For research processes, large sample size over broad range of area should be included in order to receive a better outcome because some drugs/alleles may have preference over the others (varying in different populations).
A clinical study can be explicitly stated in terms of “A primary pharmacogenetic” study when the research is based on “varying responses to drugs and the determination of the genetic mutations underlying these variations.” This can only be fulfilled when the experiment is appropriately powered, reflects on the adverse as well as intended effects of drugs, examine clinically-relevant end-points, include studies of currently neglected drugs and disease areas and covers a large population for the determination of results and comparing people from different ethnicities based on the drug intake.
“As more reliable information begins to emerge on alleles influencing drug response from larger, better designed whole genome and candidate gene studies, focus will need to shift to the critical evaluation of the predictive performance of genetic tests in clinical practice, including studies of cost-effectiveness.” The statement implies the overpowering of “reliable information” on the pharmacogenomics field of study because of its inability to present with “decent research” in certain areas. Although some articles seem to explore information on cancer related diseases, still it does not cohere to the core task of pharmacogenomics. Due to some discrepancies, studies should include the drugs which are currently ignored and not given enough importance to. Furthermore, answers may lie in those drugs which are not even looked upon as efficacious. Applying different strategies while experimenting might be a beneficial method to approach a task such as this. Authors might be focusing and relying on “reliable information” and further ignoring the research in the field of pharmacogenomics. “More reliable information” is emerging due to evidence found on loci influencing both drug response and adverse effects that might form the basis of predictive testing for close adjustment or avoidance of toxic treatments. The repetitive use of particular genes to predict certain results may give rise to side effects which hinder this field of study. To better the clinical experiments, it is important to examine clinically-relevant end-points and adopt an explicit, systematic and comprehensive search strategy. It is very important to be able to know the key strategies in order to become successful in publishing a research article. Overall, I feel this scholarly journal was an eye-opening and led me further understand about the issues pertaining to pharmacogenomics.
A Review of a scientific study is necessary for verification and critique purposes however too many of these “meta” analyses are really not productive. Academic time is being wasted on an excess of these reviews. I believe this is happening because this field is very interesting and perhaps authors feel they can ride this wave of popularity. To truly complete a primary clinical study would require original research and findings. The statement on page 12 is in agreence with the above discussed topics. It is basically stating that more time needs to be spent on primary research of MORE genes and drugs. The article and graphs indicated that only a very small portion of the genes had received attention from research teams. To truly achieve and meet the ideal of “personalized medicine it is necessary to have more information on ALL of the genes. Having more information about pharmogenoic studies will increase cost effectiveness for health care overall because doctors and scientists will have a better idea about pathology and will not ‘waste’ money on unnesarry treatments. That is what the phrase “more reliable information” is in reference to, primary and broader research techniques.
The section entitled “Recommendations for Future Research in Pharmacogenetics” overviews some potential betterments for research. They tend to focus on broadening research, for example, “be conducted among individuals of non-European as well as European ancestry include studies of currently neglected drugs and disease areas”. The first of these deals with race and ethnicity. Previous medical studies have indicated there are significant differences in how different races and ethnicities bodies respond to various things. For example, the Native American population is currently plagued by diabetes in a much higher than average instances that regular America. Their diets until the past 65 years was very low sugar and lean, the introduction of processes foods into their diets has sent their liver, pancreas, and kidneys into shock. They do not naturally produce enough insulin to process the high fructose corn sugar so common in processed foods. Researching things like this Pharmocogenitically for various races can give science and healthcare a deeper insight into more health issues and in turn arm the medical community to properly deal with these diseases for many races. America and Europe have seen huge influxes of Asian and south American immigrants all in need of treatment. Conversely studies on other races could turn up with something positive that could be applied to the population at large. The same is true with researching a broader variety of diseases.
The fact that a larger amount of the papers surrounding pharmacogenomics are reviews and not primary research articles is a problem. It is a problem because review articles evaluate and write about the specific topic or problem that has already been studied. Primary research articles are better because they give you first hand information and more precise and original results. I think this is happening because the reviews are written based on already proven experiments and show us the results that were intended, meanwhile the primary research articles can show us different outcomes such as the adverse or undesired outcomes. The article states that out of 102,264 articles only 1,668 (1.6%) of the articles where shown as original research. The reasons the authors give for this is that the FDA has limited the amount or specific tests that can be done on drugs so it is hard to come about new primary research articles. People have high expectations of this field and its research in medicine, but have little realization that the goal of being able to distribute personal medicines will need much more researching to be achieved.
A clinical study is one where once a drug is determined safe by the FDA; it can begin testing on humans to determine the effects and safety of the drug. A primary pharmocogenetic study is a study on a drugs effect on genetic variation. For a clinical study to become a primary pharmocogenetic study the research and experiments done must be more detailed. Pharmacogenetic studies deal more with the vulnerability of certain loci to diseases to help achieve personalized medicine.
With more reliable information on alleles and drug response, there are going to be more specific and detailed tests conducted on the alleles to see the side effects of drugs. With the FDA only approving 4 tests on drugs, pharmacogenetic tests need to expand on not just conducting tests on the common loci and genes, but on many others to see all the side effects of the drug. Authors expect these tests to provide more results and help to achieve their goal of personalized medicine. More reliable information is emerging because they will now have more results and effects to study and they will also have to take into account the cost of the drug and research being done against the number of patients being helped by the study.
One of the authors “recommendations for Future Research in Pharmacogenetics” is to give due emphasis both to adverse as well as intended effects of drugs. The intended effects of a drug are the desired results and unfavorable results of a drug are known as the adverse effects. The authors’ recommendation means that the undesirable results should not be left out of articles or reviews as they usually are. Companies figure if they only show the good side effects of drugs and leave out or don’t fully test the harmful side effects of the drugs, they will be able to sell them and are putting people’s lives at risk. For example in the article it states that most of the pharmacogenetics studies done for cancer, neurology, and cardiovascular disease had 1190 studies (71.6%) evaluate the intended effects and only 210 studies (12.6%) which is about 1/8th examined the adverse effects of the drugs.
It is a problem that there are more review papers written than primary research articles. There is only a certain amount of review papers that can be done on a research experiment. Scientists must begin to do new primary research experiments with new genes that haven’t been studied as much. There can continue to be review papers as these are necessary but you need new experiments to write these papers on. I think that there may be a couple of reasons that this is happening. The first is that people don’t want to do research on genes that they don’t know everything about so they continue to do research on the same genes. The second reason is because while there may have been more research studies done than are actually published scientists don’t want to publish them if they had negative results. A final reason is because there are some scientists who know that it is easier to just comment and write on another scientists research than to actually do an experiment themselves.
As defined in the paper, “A primary pharmacogenetic study was defined as one in which the title of the study or the stated aims or purpose within the text of the abstract indicated that the primary intention of the study was to investigate the effect of genetic variation in drug response.” In other words a primary study is one in which, for example, a certain drug is given and a certain gene is then looked at to see if there was a reaction. What this paper calls to do is to increase the number of secondary studies in which a drug is given and many genes are looked at to see if they are affected or not. A problem that the paper discusses though is that negative results are almost looked down upon and would not be as likely to receive publication. The scientific community needs to realize that negative results are just as important as positive ones. That we are now one step closer to fully understanding a certain drug because we know what genes it doesn’t effect. The publication of these negative results might also stop other researchers from testing the same gene when they could have been spending their time and money on a gene that they do not know if the drug effects or not. Also the paper states that there are many studies done on only a small number of genes. This is because we already know these genes’ biological mechanisms but we also need to start researching other genes as well and if they don’t want to test drugs on them because they aren’t sure how they work then more effort needs to go into researching these genes so that we can get a better understanding of them and progress forward with new drug research on different genes.
On page 12 the authors state, “As more reliable information begins to emerge on alleles influencing drug response from larger, better designed whole genome and candidate gene studies, focus will need to shift to the critical evaluation of the predictive performance of genetic tests in clinical practice including, cost effectiveness.” This means that sometime in the future we are going to get to the point where we can map out a whole genome and tell a person whether or not they should take a certain drug because of the effects that it might have on their genes.
One of the recommendations for future research in pharmacogenetics that they give is to increase the sample size. By researchers doing this they would actually be accomplishing a other recommendation on the list as well. One is testing among not just Europeans but also people of non-European ancestry. This could happen because the more people that you pull into a study the greater variance you are going to have in their nationality and will most likely pull in people of non-European heritages. However there should also be tests specifically done on this group of people as well. When a drug is released it is only tested on a small group of people (figure 5 shows an average of 100 people were used in pharmacogenetic studies). This amount of people it is being tested on is obviously very small compared to the number of people who will be taking it when it goes onto the market. By only having a small number of people you are decreasing the amount of different effects that you will get.
1. According to the figure 8, of the 136 studies (n=136), 37% were original research, with 30% being reviews. Also stated, the ratio of reviews to primary research was approximately 25:1. Of 4,674 articles (including reviews and editorials) only 183 were original articles. This is clearly a problem since a lot of attention is given to what is already done, rather than trying on a different field. There are some common genes that are being studied over and over because researchers predict that they have association with the drug so others continue on this same matter. But if they were to expand on their research by conducting experiment on other genes, it might’ve been more productive. The authors give the reasoning behind meta-analysis that meta-analysis have been used as a way to strengthen the results of genetic effects on disease outcomes
2. Primary pharmacogenetic studies are considered to be those whose main intention is “to investigate the effect of genetic variation on drug response.” Any article that had this aim stated in title or in the abstract was considered to be a primary pharmacogenetic study in this research.
3. The authors are expecting more improvements in the field of pharmacogenetic studies. Improvements should come from more usage of meta-analysis of the genes studied, with up to date online and datas resources, having larger sample size while doing primary studies, focusing more on genes that have adverse affect, along with studying the rare and structurally different genes that might have larger impact. More reliable information are emerging in the sense that studies are now being conducted on the whole genome of individials and figuring their association rather than doing a large-scale study and figuring out the few who face adverse effects. The authors belive that along with these improvements, more studies need to be done the genetic tests themselves and the cost-effectiveness.
4. “Give due emphasis both to adverse as well as intended effects of drugs”
Conduct studies that try to figure both the good and bad reactions of drugs. Instead of publishing just on how effective the drug is, also include where it went wrong or reacted differently.
Imagine taking medications that are personalized according to your genes. The effects of the drugs are never too strong or ever ineffective, but just right. You do not have to experience dramatic side effects. You do not have to go through and try hundreds of medicine, trying to find the one that works the best for you. I, for one, am excited about this idea. However, there is just too much problems that arise when studying pharmacogenomics, which is the leading reason why there are more reviews than primary research articles. It is easier to write about something that other people have studied and researched on than to do your own research. It takes a lot of time and effort, and in the end, sometimes the results are adverse effects. Researchers might not want to post their findings if their research does not contribute to the knowledge of pharmacogenomics. Reasons that the authors state to explain why it might be hard to conduct experiments in this field are “inadequate sample size, suboptimal capture of genetic variation, and significance chasing” (2). The sample sizes that the researchers have to work with are too small to come to any distinct conclusion. It is hard to get a huge number of people to participate in the studies. Some people may not want to participate in the studies that are controlled due to fear of adverse effects and lack of privacy. If the study is not done in a controlled environment, then there are too many variables to consider, such as the lifestyle and ethnicity of the people, and environment that the people live in. The author mentioned how most of those that were studied were of European ancestry. There should be more variations, especially genetically. It might be easier to observe the effects of unique gene sequences on drug responses than a trait that everyone has. Even after the studies are completed, researchers have to prove that their research held some significance. Moreover, some studies might not even be considered as pharmacogenetic studies or even included in this meta-analysis that the authors wrote. For example, in order for clinical studies to be considered a primary pharmacogenetic study, the purpose of the study is to examine how the effects of drugs vary based on the kinds of genes that the person has.
According what the authors stated on page 12, even after we do indeed get a better grasp of how the genes influence the effects of a particular drug on a specific person, we would then need to figure out a way to accurately predict the results in a clinical setting. Researchers would need to create a genetic test that could foresee how the drug would respond based on a person’s DNA. Then afterwards, we need to figure out a way to distribute the genetic test without costing too much money. The author is trying to imply that there is still more work that needs to be done. It is not going to be an easy task. It is a never-ending process. Once more research is done, eventually we will learn how another gene affects our intake of drugs. Pharmacogenomics is still a new field and it is a growing. More dependable information will be gained once people start to understand how to do their research in a way that there will be more information on genes that were not studied before. Also, when groups of researchers lay down a set of criterias and study similar variables, they would be able to correlate their findings with other groups performing the same experiments. It would be similar to performing repetition of the experiments but in different settings. The patterns would be easier to find and verifiable conclusions can be made if all the groups have the same results. The differences can then be further studied. The differences could be the result of a variation in gene sequences. Furthermore, once people understand this field and understand it’s importance, more people might flock to do more research. Also, more research might be done if people understand how to perform their experiments and what to do, such as some of the advices that the authors offer at the end for those who plan to do future research on pharmacogenomics.
Even though there are numerous advices that the authors recommended for those who plan to do further research in pharmacogenomics, the one I think that is most important is to perform studies on everyone, not just those that has a European background. According to the discussion section in this article, most studies were conducted on subjects of European ancestry, specifically those that resided in Europe and North America. It is bias to only study a small group of people. There is insufficient amount of research on other ethnicities, especially those who are more susceptible to a certain disease than others. Even if majority of everyone’s genes are the same, there are some differences in alleles or gene sequences. It might be easier to observe the effects that the drugs have on people of difference in background. It might be easier to identify the specific gene sequences that make one ethnicity more inclined to experience the dramatic effects of side effects than another since the differences could be more obvious.
Pharmacogenomics measures an individuals response to internal drug activity. While reveiwing the field synopsis of pharmacogenomics, critics were able to identify issues that may affect the way we run our health care system today. With our technology advancing, we hold high expectations from the people we see treating us on our health problems. It seems as if every other day there is some new vaccine for some new virus that doctors everywhere are recommended. The real issue at hand is the fact that these are all new viruses, and all new vaccines; can we really know how they will affect us? Are the sufficient? Or is this all just one big risk were taking based off of a few mere testings. Most critics you find today are basing their knowledge off of reveiws rather than primary research. The only way to better something to test and retest. This is a rising issue because we are all individuals, who although are made the same way, do in fact have different reactions. This could lead to an all time low failure to validify the relationship between each drug and each illness with each human. The failure to properly assess the situation is due the lack of reaching out. An easy soultion would be to broaden the horizons of the sample group. Perhaps widen the ethnicity range, age difference, weight and body build, sex, blood type, and a best attempt to narrow groups down based on similar genetic information. In order for a clinical study to become a primary pharmacogenetic study, there must be a intricate examination of drug responses in relation to a wide range of genetic variation. As we move through time, more reliable information is being demanded by the people. People want the best healthcare for the cheapest amount they can recieve it. Hence why it is vital to keep studies and aid cost-effective. With so many diseases, terminal, and common, people are easily scared. They seek more reliable information to confirm that what they are paying for, and receiving in the health care field is actually going to help, that it is helping correctly, and to be assured they are not putting their bodies at any risk. Some authors have dished out advice for the future pharmacogenomists; such as including and spread sheet of how certian drugs have reacted with specific diseases on certian races, ages, sexes, body types, etc. Giving people the oppertunity to evaluate the risks they are taking might take some of the pressure off of the system when they are taking chances on newly arrived vaccines. It will allow people to feel safer and less at risk.
Fatima Taylor
01/28
“Pharmacogenetic Studies”
This article discusses concerns and the issues involving pharmacogentic studies. Pharmacogenomics is a new and improving field of science, therefore several studies and research that has been done in this field is not conclusive. A lot of information in pharmacogenomics is still in the research and theory phase. This article critiques pharmacogenetic studies that have been done and lists improvements that scientists need to factor in when conducting research in order to further develop this field.
1. Pharmacogenomics is receiving a lot of buzz because if proper evidence is found, in the bear future we could have personalized medicine in almost every aspect of healthcare. Because it is such a new field and not largely understood, research is limited and scientists are still unsure of how to go about conducting proper studies. The reason why there are so many reviews rather than primary research studies is because scientists do not have all the facts. A lot of pharmacologic testing relies on what we know as a scientific community- which is a certain number of genes and a certain number of drugs, rather than all that apply to pharmacogenomics. A lot of information in pharmacogenomics is still largely theory in part, so it is difficult to conduct studies without proper amount of research. The fact that there is more reviews than actual studies poses a great problem because it discredits the field. Properly conducted research is what backs the claims of personalized medicine and provides more factual evidence than scientific opinion. The authors explain that this issue is cause by scientific studies only being performed on known genes that are affiliated with certain drugs, rather than new ones. They also explain that several studies have been performed but not published, or could have been published but under a name different than pharmacogenomics. This makes it difficult to locate studies. Also, a lot of genetic medicine is still theory, so more reviews on the study are out their than actual studies.
2. A clinical study is primary because it involves valid, well planned and discussed case studies. Clinical studies can in pharmacogenetics can be described as primary because they will attempt to find answers to specific drugs that are related certain diseases (whether genetic or not.) These studies will examine all aspects if the drugs effectiveness on the patient (how does it make them feel? Is it working biologically? Is it compatible with the individual’s genotype? Etc.) Clinical research in personalized medicine will encourage treatment and diagnoses of illnesses years before the person even begins to show symptoms by studying all aspects of one’s genetic makeup. These clinical studies will make personalized medicine even more possible. They will be primary because they will include a wide range of individuals with different genetic makeups and determine how to treat ailments ranging from allergies to Alzheimer’s disease.
3. What the authors’ are explaining is that in order to expand in pharmacogenomic testing, we must move out of the theory phases as new research is emerging. We must begin to perform actual clinical studies in order to expand the field of personalized medicine. Individuals will need to be carefully tested and examined based on their genotypes of a period of time in order to observe the results. Researches have to begin to specialize as well as expand their study methods in order to be able to predict an individual’s biological affinity for a drug. The authors’ are expecting the field is expand as more and more people want treatments for terminal illnesses (such as Alzheimer’s, Parkinson’s, respiratory diseases, genetic diseases and cancers.) As technology is improving, so should our knowledge on personalized genetic medicine. More research and studies will need to be conducted involving alleles, DNA and one’s genotype. These studies will be expensive to perform so costs and funding are a major issue. Therefore, limiting the costs on studies will be very important and well ask stressing the importance of well planned experiments before millions of dollars are spent on useless outcomes. More reliable information is emerging because people wish to find cures and treatments for diseases because they are aware of the possibilties.
4. One of the author’s recommendations for further research that will prove to be conductive is to expand the study subjects’ gene pool. To conduct studies on individuals of European as well as non-European decent, will open up new possibilities in pharmacogenetic testing. If scientists were to conduct studies on individuals of all genetic backgrounds and ethnicities, they would greater expand the knowledge pool of different genotypes and genetic diseases. Examples of this would include- performing studies on people of Asian decent and American Indian decent. These people have different genetic makeups and inherited different genes based on their genetic backgrounds. It would also be good to test people of African decent because they have several different genetic dispositions than do Caucasians (such as sickle cell anemia, and large lactose allergy populations.)
This week’s article discusses the field of pharmacogenomics and how this field produces an abundance of secondary or review articles but lacks substantial primary research articles. This is a problem because in order for a field of science to expand, extensive primary research must be conducted, published, and distributed. Reviews and analyses simply provide repetitive information. Primary research provides new information and advances. There are several reasons that this could be happening. One of them is that it is easier for scientists to write based off someone else’s hard work. Another reason is that scientists in this field may be lacking adequate funding and support. A third possibility is that research in pharmacogenomics must be tedious since there are so many genes, diseases, and drugs available today. It is an overwhelming amount of topics and genes to study. Lastly, in the realm of time, genetics (and pharmacogenomics) is a fairly new field of science that to this day is still being researched and studied. The authors suggest that there are so few primary research articles in pharmacogenomics because the studies are focused mainly on cancer, cardiovascular and neurological/psychiatric disease and are mainly conducted in North America and Europe. This limitation in disease and subjects limits the research that will be produced.
A clinical study is a study in which a drug’s efficacy and safety are tested. In order for a clinical study to become a primary pharmacogenetic study the drug’s efficacy and safety must be directly correlated to the subjects’ genetics. Specific genetic loci would have to be tested and observed. The researchers would have to study how a person’s genetics affect how the drug works and how they react to it. The clinical study would have to look deeper than what type of side effects occur or if it cures the ailment it was created for. The researchers would have to tie genetics into their reasoning.
The quote from page 12 means that as more reliable information emerges, researchers of pharmacogenomics must determine if genetic testing for drug response will be effective and reliable. The authors also suggest that researchers determine if genetic testing will be cost-effective, meaning they will have to determine if the cost of genetic testing will be beneficial and profitable in the end. As I mentioned earlier, genetics is a relatively new field in science. Since the human genome is so large, it is continually being studied which is why new information is always emerging. Science is a field that consistently builds upon the results of yesterday.
One of the recommendations for future research in pharmacogenetics is that it should be “conducted among individuals of non-European as well as European ancestry.” The authors mentioned earlier in the article that one of the reasons that pharmacogenomics lacks primary research articles is because research is mainly conducted on people of European ancestry. People of all different races use medicine. In order to conduct relevant research in order to one day be able to deliver “personalized medicine,” the results cannot pertain to only one race. For a study to be relevant and accepted it must be conducted on a variety of subjects, not just Europeans. A primary pharmacogenomic study should involve White, African-American, Hispanic, and Asian people. If limited to one race, the results will only be relevant for that group of people and ultimately will not be the breakthrough that scientists working in the field of pharmacogenomics are hoping for.
The scientific journal brings up interesting aspects of pharmacogenomics and its state of development. The use of secondary sources in the research gave me the impression that more time was put into established research than new and upcoming experiments, even though the focus was on the pharmacogenetic studies. The overwhelming amounts of secondary sources used in the article made me wonder if the statistics were accurate or not since there was no review of how the experiments could have been improved.
The study of different genomes and their links to diseases play significant roles in the research of the roles of genes. The wide variety of usable results seems limited by the desired results the researchers seem to want. The limited amount of primary research used in the article was said to be due to the different names used to title different research articles that are basically phamacogenetics related. The use of reviews eliminates some of the effectiveness of the study since many reviews would not have the detailed results and methods explained in complete depth, including results found that are not tied to the original hypothesis. The discovery of such ‘accidental’ results would be beneficial since there are a wide variety of proteins that a gene can code for. Primary studies, however, play very important roles in identifying genomes and their functions/defects. If the hypothesis of an experiment is proved to be correct, the results would be very reliable primary sources.
The sample sizes used in prior studies were said to be too small and unreliable. The article said that new studies have more reliable sources since such factors like genes from different cultures will be taken into consideration and also larger sample sizes will be used. The studies of different genotypes would help take a step forward towards personalized medicine.
A few recommendations for future research in pharmacogenomics were mentioned in the article. The utilization of whole genome analysis where mechanisms are uncertain would help identify the functions of genes and the proteins they encode for. The expanded knowledge of certain genes would help bring up future studies and more focused studies for specific diseases such as the mechanics of a gene that encodes for metabolism regulation. The knowledge of the genes mechanics may help improve the lives of those who have irregular metabolism.
The paper discusses the fact that pharmacogenomics often relies on reviews on other scientists’ research isn’t helpful in progressing in the field because there isn’t any new information presented. The human genome is so complex that in order to study it and its behaviors in relation to a drug is tedious work. Scientists may be intimidated by the amount of work they have to do in order to accurately collect the data so they would rather report on the findings of other people to save themselves the hassle. The author’s reason that there are so many different ideas about gene function in relation to drug effects, it’s hard to choose from which approach should be taken. This frustrates many scientists who resolve to writing about data already published.
A clinical study would be eligible to be primary if its’ stated purpose is to “test genetic variation in drug response”.
When the author states that there are more reliable information emerging means that the studies being done are beginning to narrow down the list about drug response in relation to the human genome. This new information enables people to begin cutting out the genes that obviously do not play any role. More reliable information is emerging because of a “better designed whole genome and candidate studies”.
One of the author’s recommendations is for studies “to be conducted among individuals of non-European as well as European ancestry”. This would open up studies to be done with a more culturally diverse population. The human genome is vast and the author’s suggestion of taking this fact into consideration is a valid one, especially since people of non-European ancestry will also be taking the pharmaceutical drugs.
While reading the comprehensive scientific journal “Fulfilling the Promise of Personalized Medicine?” the writers want us readers to grasp one main concept and this is how the study is being conducted. This paper is a wide collection of research put together, intended to investigate a particular problem and also present some solutions to these problems. These writers are taking other individuals data and are using this data to address the experimental data that is encountered, this is also referred to as a meta-analyses. It is seen that a lot of these research articles are reviews rather than primary research articles. This is beginning to be a big problem because if we constantly have scientists just commenting on a few primary research articles we will never get any further in pharamacogenomics. They are simply just circling back missing the big picture which is to discover new research on other genes that may potentially be clinical markers but instead they choose to focus on particular genes that they already have a vast amount of information on. These scientists probably are not committed to the amount of work and difficulty in conducting a primary research. The author also mentions that many scientists are afraid of not achieving the expected results.
In order for one to have successfully conducted an “A primary pharmacogenetic” study there must be direct interaction with the topic at hand. Being that a clinical study is well structured it must clearly state the problem and propose and list the conclusions of the experiments. Also it may list possible solutions to these problems. If the results match the primary purpose of the experiment, then it was successful.
As more information emerges on the pharmacogenetic field it needs to focus more on the genes that were not being looked at. There is a wide variety of information on the genes that they chose to focus closely on such as for cancer and cardiovascular but with the exploration of other genes we may further progress or find answers to certain questions posed.
A wide list of “Recommendations for Future Research in Pharmacogenetics” has been proposed. One that they suggest is to increase the number of people in the experiment. Also include studies of currently neglected drugs and diseases areas. This will help in various ways such as these neglected drugs just may be the answer to the problem and or maybe the potential clinical marker. Going back and forth in a circle won’t further progress our knowledge in this field. Therefore following through with these recommendations will help develop the field of Pharmacogenetics.
Yamine Richard
Tox 1401
Professor Gillespie
Jan. 28, 2009
Why Aren’t We Fulfilling the Promise of Personalized Medicine?
In this article, it is considered a problem for pharmacogenomics to constantly make reviews rather than primary research articles because it limits the progression of studying complex disease genetics. The primary research of a pharmacogenomic that contributes to the recent success in the identification of genes for common disease is regarded more valuable than the recurring genome-wide analysis. The reason behind this reoccurrence directly results from the high expectation pharmacogenomics encounter while attempting to extract the newest knowledge for the benefit of the patients. However, these benefits become inadequate advances in medicine when research reviews are positioned above studying how the variations in the human genome affect the response to medications primarily. The authors also believe that non-efficient research blocks the development of personalized medicines and establishes failed replication and validated genetic associations.
Within the article, a primary pharmacogenetic study was defined as one in which the title of the study or stated aims or purpose within the text of the abstract indicated that the primary intention of the study was to investigate the effect of genetic variation on drug response. It is a study in which pharmacogenomics are looking for a direct interaction.
The statement on page 12 addresses the necessary evaluation of the effectiveness of genetic tests that needs to occur. This evaluation will utilize different metrics rather than the conventionally reported odds to ratios or proportion of variance explained. Through this evaluation, the authors are expecting significant improvements of personalized medicines in healthcare. When regarding “more reliable information” that is emerging, the authors are referring to the methods in which genes were discovered. In the 1940s, we knew about their biological mechanisms. However, it is insufficient to think that these genes can synthesize protein products when in actuality they might not be good markers.
One of the “Recommendations for Future Research in Pharmacogenetics” is to give emphasis both to adverse as well as intended effects of drugs. It has been observed by the authors that the intended effects of drugs are commonly explained by researchers whereas the adverse effects are often ignored. The authors of this article believe that documenting the adverse effects will assist pharmacogenetics in the development of personalized mediciations. For instance, the medication known as Thalidomide was commonly used during the late 1950s as a successful inhibitory effect on morning sickness in pregnant women. However, it was soon discovered that the adverse effects were horrific because it caused severe birth defects. When the adverse effect of a drug is provided, researchers can have a better understanding of how to improve a medication, as well as whether the treatment of a disease by a drug is worth the long-term risks that are involved.
Many people simply avoid the tedious work of writing a research paper. Reviews are just more simple and quick. Ultimately, this is a problem because it hurts the pharmacogenomics research field and the development of personalized medicines. It also sets an example of a poor research format and the paper helps to design a better research approach. According to the paper, primary research articles in the field of pharmacogenomics is due to a lack of factors such as small sample size and a candidate gene approach opposed to a genome-wide analysis have restricted and prevented the study of pharmacogenomics to go beyond just reviews and develop into primary research articles. A primary pharmacogenetic study is a clinical study in which the drug response is studied in relation to the person’s genome. The study had to have met the screening requirements by MH. The quote on page 12 states that research on alleles influencing drug response from whole genomes is needed and is essential. If it can be done, it will allow us to make this shift to personalized medicine, which would be more reliable information because it will be more specific according to the human’s genetic variation and thus more effective. This in turn will be more cost-effective because in the long run this method will be more affordable and more beneficial financially and medically. The author states that including “studies of currently neglected drugs and disease areas” in future research studies will help the pharmacogenetics field. This means that drugs or genes that have been avoided should be investigated because it may hold new prospects and advantages. People tend to repeatedly work with the same genes because the information already known about them allows us to do research with an expected outcome in mind as in a prospective study. If we work with those genes that are left out, we may discover new findings that will help in the development of personalized medicine.
In this paper “Fulfilling the promise of personalized medicine?” it mainly introduces the problems that pharmacogenetic researches are facing in this century. The paper first defines the important terminologies that are essential in the field of research, such as disease category, gene nomenclature, and primary/secondary pharmacogenetic study etc. pharmacogenomic research is a type of scientific research base on the effect of a particular drug on certain type of the human genes. The main idea of this research paper is to distinguish the pros and the cons that the scientific world is facing when scientists are mostly using meta-analysis to publish their research. When a scientist does a pharmacogenetic primary research, they are directly stating the purpose of the experiment and expect some kind of result at the end. If no specific goal states at the abstract, then is it a secondary pharmacogenetic research. The author points out problems base on the methods people did research in the past. One of the major problems is that people are not doing their own research and investigation, they just simply taking other people’s old data to use as proofs and get similar results as previous experiments. Another problem the author purposes is the absence of constructing clinical studies on minor genes that we do not have any information on, instead we are constantly conducting experiments on the genes that we have many prior knowledge to. The positive side to this practice is that people can get improvements on the results when they repeatedly do the work, and the results may each time come to be slightly different due to the precision of each laboratory. The negative effect of this era’s pharmacogenomic research mainly argues about whether or not the idea of only conducting experiments upon “popular” genes is the right way to help the science world to continue progress. The author did not recognize any progress base on the research methods, because all they are doing is standing in a circle without any steps moving forward. The scientific world will only improve as they conducting new researches in the pharmacogenetic field.
The author stated at the last page of the paper “as more reliable information begins to emerge on alleles influencing drug response from larger, better designed whole genome and candidate gene studies, focus will need to shift to the critical evaluation of the predictive performance of genetic tests in clinical practice.” In this particular statement, the author is commenting on the present day genetic tests. The good news is that the population of the gene tests are increasing and creating more accurate test results. As the scientists analyze the results, they usually compare and contrast individual’s health conditions base on the groups they are put in: one group had the pharmacogenetic test and the other group had none. As more high-tech laboratory instruments are being produce in our society, the cost of getting a proper treatment is also increasing. The author suggests that we should have proper judgment on deciding the importance of have a particular treatment. One of the recommendations the author gives is “to conduct among individuals of non-European as well as European ancestry. I think this suggestion is very significant because it can reduce bias. When we conduct an experiment we should consider all the race and gender differences, maybe a particular race might create a special effect toward the drugs they take and this small effect can be very useful when gathering data and getting the results at the end.
There are various factors that influence the problem of why the field of pharmacogenomics has not yet fulfilled the promise of ‘personalized medicine’. Everyone in this world has their own genetic differences which lead to the different drug responses. If more research is done on ‘genotype based predictive tests’ or ‘genetics’ rather than the use of drug efficacy, there would be fewer difficulties in disease genetics. There are many people doing research on how to improve the components of personalized medicine that expect to find reliable sources. However, how can a researcher make his or her own reliable research article if the majority of the research available consists of reviews and commentaries rather than primary or direct interaction of investigated effect of genetic variation on drug response? It is a major problem because according to this article, 94% of the research is made of review articles and out of the remaining articles only 1.6% fulfilled the criteria of being primary research articles! (Figure 1)
Researchers should have a wider variety of information available to them that fit the criteria of a great article. If there is a greater amount of reviews over primary research articles, then the researcher is getting information that continues to be an analysis of an excess amount of analyses that may have been wrong or not particularly wrong but on “candidate genes rather than genome-wide analysis”. In other words, our population is becoming more diverse everyday and studies are done on the “typical things” instead of taking consideration of bigger sample sizes, non-European/American regions, and focusing on certain conditions instead of a wider range of disease. According to the authors, there is a larger volume of reviews and commentaries over primary articles because of the closed evaluation of ‘common variants’ that should utilize large sample sizes.
A clinical study that is considered a “primary pharmacogenetic study” is one that addresses the ‘purpose or aim of the article within the test of the abstract’ to be about the “investigation of the effect of genetic variation in drug response.” In a primary pharmacogenetic study there is a direct interaction to do the goal of the article and it has genuine information to support the aim of the article.
“As more reliable information begins to emerge on alleles influencing drug response from larger, better designed whole genome and candidate gene studies, focus will need to shift to the critical evaluation of the predictive performance of genetic tests in clinical practice, including studies of cost-effectiveness.” Once studies begin to improve and researchers utilize better tactics for the investigation of drug responses due to genetic variation, such as using larger genomes and candidate gene studies, there will be more ‘secure evidence available on loci that influence the drug responses and adverse effects’. This will create the predictive testing for dose adjustment and prevent any toxic treatments. There is more reliable information because they are using a larger and better designed whole genome and candidate gene study instead of using the same type of gene for the diseases.
Out of the many recommendations that are offered for future research in pharmacogenomics, I believe that one of the most vital recommendations should be to “enhance the likelihood of large effect sizes necessary for the generation of usefully predictive tests through the study of rare or structural genetic variants, and/or more extreme phenotypic differences in response or toxicity ”. Large genetic effect sizes are used to identify genetic loci that have uncommon and adverse effects of a drug is utilized for the study of genetic variants. They have larger effects because these variations will differ by ethnicity mainly due to the high variation in the allele frequency. A surrogate for genetic variation, phenotype, was excluded from the search for the pharmacogenomic study and it should be included to an extreme level for toxicity or efficacy for the improvements of pharmacogenetics in the future. Personalized medicine has not been initiated because of our lack of expanding in research through studies with a spectrum of the genotypic backgrounds.
The article “Fulfilling the Promise of Personalized Medicine” tells me the field, “Pharamacogenomics,” is a fully challengeable and worthy to investigate part for the bettering of human health. However, at the same time, the paper points out the problem that not many scientists participate in research as a primary study, but rather review or comment upon others’ work. Rather, I thought scientists always kept up to date on their knowledge of their field of study. But, reviewing and commenting upon co-workers’ research may be another way to study their interesting field. Oppositely, those exercises are not contributing development of the pharamacogenomic science because it does not increase number of sample data and different cases of outcomes. I think this phenomenon comes from time spending with patience, difficulty of finding test participants, and collecting various genomes. The authors in this paper tell me small sample data will give imbalance of the information for different conditions of cases. Also, studying a subject that already studied by someone else gives limited possibility of developing predictive tests for disease.
A clinical study is “A primary pharmacogenetic” study, which sets up or designs the research having a purpose, the effect of genetic variation on drug response. As a result, it provides large sample, different popularity, and various cases of drug responses and adverse effect. Moreover, the study needs to follow the three steps: how do you study, what you focus about, and how do you report it.
The authors say, “As more reliable information…including studies of cost-effectiveness.” It means by participating and focusing more about primary study, scientists will approach diseases attack more precisely and effectively. On top of that, large amount of reliable information can make predict of drug response and adverse effect. The authors expecting no more reviewing and commenting previous researches, but wants to emerge various sequences of a primary study from rare case. Also, authors talk the result sometimes not come out easily by following well designed research; sometimes we need to take a time to try different trials or different thought to approach the research because sometimes we can find the result from unexpected place. By doing those tries, finally the scientist would have more reliable information.
“Primary research in pharmacogenetics should enhance the likelihood of identification of large effect sizes necessary for the generation of usefully predictive tests through the study of rare or structural genetic variants, and/or more extreme phenotypic differences in response or toxicity.” Pharmacogenetic study is necessary to predict the effect of a certain drug and prevent binary outcome. Human beings are not same factory product s that they contain different genes. So, some people have different response for a certain drug than common people have. For insistence, the paper gives example of rare case research,“ heparin-induced thrombocytopaenia (frequency 0.5-2%).”
This paper, reviews the problems that pharmacogenomics research has and how these problems are preventing “the promise of personalized medicine”. The major problem in all of the research done is that it is not primary research, meaning that many of the analysis done come from preexisting data. The authors give a couple of reasons for why scientists use already existing data instead of conducting their own research and producing their own, mainly it is due to the fact that they do not always get the expected result. I have come up with another reason. Since a lot of the research that’s already been done focuses on a certain group of genes, some scientist may find it wasteful to conduct research on a gene that has some preexisting data. So they examine the data they need and write reviews about it. This creates a problem because more and more scientist would get use to just reviewing data and primary research would be slowed. Furthermore, the papers discussion is on ways that would make pharmacogenetics research better. For example, many of past researches have been conducted on small populations and on the same continents, given rise to results only reliable to those conditions. But once a drug is released into the open world, the many different climate conditions in different continents and the different races that inhabit them come into effect. Another example of how research can get better, stated in the paper, is by not only using the correct outcome but the opposite of it the mistakes. The mistake can lead to some new conclusion in another gene.
The authors almost at the end of the paper state that “As more reliable information begins to emerge on alleles influencing drug response from larger, better designed whole genome and candidate gene studies, focus will need to shift to the critical evaluation of the predictive performance of genetic tests in clinical practice, including studies of cost-effectiveness.” This means that they expect for more well conducted research to appear and that not only would the expected outcome be published but the adverse effects.
The article points out a primary issue surrounding the pharmacogenomics and the large volume of the papers are reviews instead of primary research articles. Why is this a problem? Because scientists are writing about what has already been done! They’re lazy! Instead of discovering something new or producing new primary research to write about on their own; they just write reviews over and over reiterating and criticizing the work of others. They are pretty much milking the system by being credited for reviewing someone else’s work. Scientists shouldn’t write reviews, they should be writing their own primary research articles, researching profound new discoveries and such instead of wasting time on what has already been done! One reason authors have concluded for this happening is that scientists have too many hypothesis and they are limited to experiment on certain drugs forcing them to write countless reviews.
What would make a clinical study into “A primary pharmacogentic” is the detailed study put into the typical clinical study. The article even includes a list of “Recommendations for Future Research in Pharmacogenetics: Primary research in pharmacogenetics should:” in the discussion. The difference between a clinical study and a primary pharmacogenetic study is that a clinical study is a FDA approved study on the effectiveness of a drug. A primary pharmacogenetic study is a study in which the aim and purpose for the experiment is shown in the abstract including the primary intention for the study of the drug and its effectiveness.
Expanding, expanding, expanding! The authors are looking foward to new improvements in clinical practice by expanding their studies with larger sample sizes! This will lead to new outcomes and more reliable information. In a nutshell, it’s all about expanding and improving expecting! Larger sample size leads to a wider expectation of results and information of a drug. Keeping in mind the cost of the new tests and experiments in comparison to those who are being medicated and helped because of the new improvements.
“Exploit existing large randomised controlled trial datasets as a resource for pharmacogenetic evaluation (e.g. SLCO1B1 variants and statin-induced myopathy, based on the SEARCH trial involving 12,064 participants) [40]” This is a vital recommendations for research in pharmacogenetics because it indefinitely improves the system for research. I like the example you used in class about how there were 50 scientists all in a lab and in reality only two of these scientist actually and physically did the research and study as for the other 48? They just reviewed and critiqued off what the two scientists did! That’s absolutely ridiculous. In addition my clinical chemistry professor told us a story of how he worked in a research lab and he started working the same time as a man named Tim. They both started at the same time yet, my professor finished his training within a month, as for Tim, he trained for as long as my professor worked there. He trained and trained and my professor knew that this man was just milking money from the system, he did not challenge himself to be better, he was a vegetable in a lab just trying to make money. We need to evaluate the studies and the scientists who work in order to look foward to improvements for the future. Evaluate, exploit, and eliminate! That’s how I look at it!
Scientific experiments were always causes that needed a ‘’third’’ party to stimulate it financially because we all know how expensive running a experiment can be. From this we can see that to do a research is not that simple because running needs support, and there are not a lot of places who will support just anybody for their personal hunt for glory. Instead big companies, or whoever is supporting the research, are looking for people with promising ideas, they are looking for people who won’t waste their time or their finances. And usually there are only a few people who did probably years of studying to come up with an idea that is safe and has smaller chances of failing. And why other people keep publishing , well this is probably because that their projects didn’t get any support, or they think that they can describe the flaws of the research and help correct it Or maybe is just like everybody thinks that they are too lazy to conduct their own research but I don’t really believe so. My point in all this is that nobody wants to waste money or resources that don’t promise success more than promises failure, so scientist then write reviews to try to develop some new idea into the picture or they just want to protect their throne by writing things that eventually gets unnoticed.
A primary pharmacogenetic study is defined as a study where the title of the study or the stated aims or purpose within the text of the abstract indicated that the primary intention of the study was to investigate the effect of genetic variation on drug response.
By my opinion the quote implies that we need to change our research because it is a fact that some drugs do not give the same results in people with different geographical areas. The point is that researches are conduct mostly in countries that have the means to do them and those countries are in North America and Western Europe, so when there are drug trials the people tested are mostly from a European ancestry. And as we know are modern world of cultural diversity has brought people from different ancestry lines with slightly different genotypes in one place, and being that the drugs were mostly tested on people with different genotypes some drugs are not as effective with all people. The author means by more reliable information the mixing of people of different nationalities making the individuals who are tested more diverse and making it easier for scientist to make a drug that is suitable for everyone.
The list of improvement never ends, in life we always tend to get to that perfection that we either have taken as an idea from others or put it there for ourselves. The Improvement that I would like to happen in modern clinical studies are, like I previously said, conducting research among people who have diverse ancestry lines. I’m saying this for the reason that people who are different ancestry lines from the small portion of the people who were in the research , based on who the drug was build, have maybe some genes that react different than in other people and the drugs can be manifested more harmful then it can be.
Science is a field fueled by research and new discoveries, therefore having a large volume of scientific papers being reviews rather than primary research articles is a problem mainly because simply put there is not much actual progress being made. Having reviews of research is definitely sometimes necessary and beneficial in order to make the most out of the research findings but however too many reviews become unnecessary and repetitive. I personally believe this is happening because a number of scientists may be detracted from the true goal of science. To clarify, I believe that the case may be that some scientists just have the goal in mind of getting their works published and therefore go about the best method of doing so. By this I am not saying that scientists are corrupt I just believe that this may be a factor as to why there are large volumes of review papers instead of actual review papers. One reason the authors give is that a lot of useful research findings do not get published because the results are negative so although there may be a lot of research going on we aren’t making the most of the findings. Another reason that the author points out that may be contributing to this problem is that scientists are limiting themselves in the researching of certain genes perhaps because instead of testing.
As stated in the article a primary study must either have the title of the study or the aims or purpose stated inside the abstract claim that the primary aim of the study is to “investigate the effect of genetic variation on drug response”. Therefore in order for a clinical study to be termed a primary pharmacogenetic study it would have to fall under those conditions, otherwise it would be termed a secondary pharmacogenetic study.
On page 12 when the authors state state “As more reliable information begins to emerge on alleles influencing drug response from larger, better designed whole genome and candidate gene studies, focus will need to shift to the critical evaluation of the predictive performance of genetic tests in clinical practice, including studies of cost-effectiveness.” they mean that the authors expect change to come to the field of pharmacogenetics, change that will help us make progress more sufficiently and efficiently. In a nutshell the authors expect the field to become more structured and have more direction. The authors believe that a database should exist where scientists can input research that had negative results so that other scientists will either be able to use the negative results to create positive results or just not repeat the same negative experiment, basically that a negative result is just as useful as a positive result. The authors also expect that in the future sample sizes will be more genetically diverse and larger and also that genetic tests should will not be conducted with a specific outcome in mind instead they will be conducted, recorded and compared to a population with a different ancestry for a larger variation of findings. Most of all the authors expect there to be a structured criteria of how to study, what the study should look like and what should be reported in the study.
One of the authors’ best recommendations for further research in this field in my opinion is the creating of a database where “failed” or “negative” resulted experiments can be stored although I believe no results are truly negative nor an experiment failed because they can be used in one way or another to further science. If there is an experiment where a specific drug has a completely different effect than expected, that experiment should be treated just as useful as an experiment where the drug did what it was supposed to do; reason being this could help with further research projects down the line. Having a database for “failed” experiments could also potentially save a lot of funds and resources because scientists wouldn’t repeat similar experiments, instead the information would be there already where it could possibly be expanded upon in the future. Overall I believe this article raises many valid points as to why the system is not at its best right now and also offers many valid ideas that could serve as catalysts to getting us where we need to be in the field of pharamacogenomics, however bringing the solutions into does not seem as if it would be such an easy task.
The setbacks that keep occurring with research have prolonged the ability to make new discoveries in the modern day world. Many scientists instead of conducting their experiments and research, write reviews about what other people done. The use of meta analysis has just been reusing the name data for over 20 years now. Instead of researching different aspects of pharmacogenomics the same genes, drugs and effects have been studied and reviewed. The article states that only about 1.6% of the publications of pharmcogenomics research have been proved original. The rest are all reviews and meta analysis. This promotes a problem that has set us back in the development of technologies and information that we should of by now already discovered. The article tries to explain on page 12 that new research should be conducted on different genes, drugs and effects to ensure new discoveries and our better understanding of pharmacogenomics.
A study defined as “A primary pharmacogenetic” study” must contain valid points to “investigate the effect of genetic variation on drug response.” The study would contain a controlled group of a specific single or group of genes and their reaction when in contact with a certain drug. The ability for your body to metabolize that drug and what genes are effected would be a primary pharmcogenetic study.
There needs to be more studies implicated to research different types of genes. As the genome becomes studied better and its drug response becomes better known studies will shift on the focus of specific alleles rather than whole genes. This can tell us with better accuracy the cause and effect of a certain drug to the genome and what effect will it have. As research progresses scientists will develop affordable way for an average person to be able to have this test.
“Give due to emphasis both to adverse as well as intended effects of drugs” is a research topic recommended for future studies of pharmacogenetics. This topic would mainly discuss our ability to foresee the effects of drugs before they are administrated just by our genetic make up. Our genome has the ability to tell us what drugs will be suitable for that specific person and which will have negative effects. This technology is still in its early phases of development due to the lack of original research on the topic. The more we learn about the genome the quicker the science of pharmacogenetics could progress.
Using reviews rather than primary research articles doesn’t give us the benefit of collecting the exact data that we need. Due to the large volume of meta-analyses, it is important to cross reference the information that is collected and identify the missing information as well. All information has to satisfy the standards of a pharmacogenetic study. When the word “pharmacogenetics” is searched in a database, very few original articles are retrieved as opposed to reviews or editorials. It is often seen that more results or sources are found when searching for reviews which is why the authors refer to this information. More often it is difficult to find primary research articles because authors of these papers must pay to make them accessible to the public. Usually these research articles are a part of private online databases which very few people have access to. Those articles that are a part of a “large journal factor” are more likely to be read by the general public. Primary research articles serve a more important purpose in these studies because it is a direct interaction with the subject matter, while secondary research such as reviews may be more complex and may not include as much information.
A primary pharmacogenetic study is one where the response to drug therapy is examined in relation to genetic variation. This drug variation can occur amongst humans or in drugs. They often study diseases such as several cancers, neurology, and cardiovascular diseases. Most of the studies are focused on evaluating the intended results as opposed to the examined results. However the adverse effects of drugs are also recorded.
The authors discover that instead of evaluating and predicting the results of genetic tests, we must shift our focus to developing techniques perform more studies with more samples. The smaller pool of genes we focus on, the less we can conclude with the information that will fit to a larger scale. It is insufficient to take a gene that we “think” is going to be important. Instead, the authors suggest we should look at the all the genes we can to confirm our results, rather than take our chances. By looking at a larger scope of genes, results will vary and more data will emerge from one study, rather than conducting several studies that will show simply the same results. When the authors say “more reliable information”, they mean we should study more genes, or more information than we are at the time. In turn, making these changes should eventually help to realize the importance of personalized medicine.
“Avoid post-hoc subgroup analysis, except where justified and powered, and report the findings with due caution.” While one is analyzing a set of results, we often collect data that we were not initially intending or looking for. If this is the case for the most part, it might be that the set up has been disturbed or has been conducted in an incorrect manner. Post-hoc results are received when the results you see are not what you expected. The results should indicate whether you’re on the right track in your research.
The deliverance of personalized medicine is having a major setback. This is because not enough research is being put through in our advancements toward pharmacogenomics or pharmacogenetics. This is a problem because we are lacking the resources to analyze gene variants due to limited amounts of published articles. According to the Medline search system as well as the MeSH and FDA, not enough research is available because most of the results are commentaries or editorials. Out of the 102,264 articles retrieved from the key word “pharmacogenetics” or “pharmacogenomics” or other related key words, 97,339 articles were recognized as reviews, editorials or letters in Medline. The MeSH term yielded more or less a similar ratio of reviews to original research, of which 4674 articles were the majority and 183 (4%) were legitimate. The reasons for this cause may stem from a variety of sources. One, people are becoming lax towards scientific field work which restricts reliable testing. Two, not enough information is readily available on a specific gene which inhibits a more close examination of the subject at hand. Both are capable of producing such effects, but in order to take a closer look on this matter, I think we have to look at the problem in a global scale or in a wider spectrum. A likely reference might come from differences in studies done outside of a country relative of other continents doing the same type of investigation or analysis. The interests of unrelated minds play a part in producing results in pharmacogenetics. For example, observers obtain different values when conducting the same type of experiment, and this is the same for tests run by members of a different community. One person might favor some analysis over the other, which another person might think otherwise. Since people are profoundly different, I think it depends on the case being studied, whether it’s independent or dependent of another party. The fact that some gene studies are preferred over adverse or suggestive ones presents a gap between gene variants and meta-analyses because people like to work on subjects that they feel more comfortable with or depend on. The authors give explanations such as sample size in genetic studies which yield inaccurate results, studies associated with articles from a variety of countries, and paucity of insignificant genes compared to more valued investigations of genes and disease associated studies such as cancer.
A clinical study is considered “A primary pharmacogenetic” study when it meets appropriate standards. These include the following: results with intended and adverse effects are emphasized, covers relevant end-points, is conducted in a more diverse background other than European and non-European, pertains closer examinations to undisclosed drugs, dealt with larger effect sizes for better predictive tests and results, and etc. These are just some of the requirements but there are others that are just as crucial.
The quote on page 12 simply translates to having more techniques and identification methods for post analysis. This means that as larger samples are conducted for tests, the quality and performance of sample testing should be enhanced in order to control and facilitate information with evaluation and get high quality results. For these kinds of results, efficiency should be maximized at an optimal rate and cost minimized because research is costly and requires taking into consideration the details and precautions. The authors are expecting to see increased field capability towards new gene variants because new reliable information will lead to a spike in exploiting techniques for evaluation and analysis to perform experiments at a controlled manner for the best results. The emergence of “more reliable information” is anticipated for particular reasons. They are emerging because whole genome association studies has presented us with a larger systematic concern for gene variants which provide us with new insights into disease, and developing predictive tests for diseases.
One recommendation for future research in pharmacogenetics is “systematically and comprehensively collating, archiving and disseminating reports of pharmacogenetic research, to high-light continuning gaps in knowledge and promote successes.” This means that the database for research on pharmacogenetics should be constantly reviewed and updated in order to filter out unnecessary articles pertaining to irrelevant studies such as commentaries, editorials and letters. This is crucial for sorting out high quality analysis and work because it encourages appropriate reviews and meta-analyses for research in pharmacogenetics.
A review of scientific work is necessary for the critique and development but as much as there are reviews, there needs to be the actual research and work to better science. 25:1 ratio of reviews to primary research is too much or rather unnecessary especially if the ratio increases at this rate because there are valuable time wasted on repetitive reviews instead of actually figuring something out. From the scientists perspective I can see that many write reviews on previous research that are popular and are the central concern of the time. Cancer, cardiovascular disease and neurology/psychiatry are very crucial concerns that Pharmocogenetics wants to go in depth to but as they garner too deep into one type of gene they tend to ignore other genes. I think that doing original works are being ignored due to the difficulties of completing a primary clinical research. Many probably have tried but got an unexpected result which is why they felt it’s not fit to publish since science is “precise” especially in the lab field which like “expected results”. In my opinion unexpected results are worth publishing as well as expected results as they provide with something scientists can work from and learn from. Writing reviews seems to be the trend as it is easier for scientists to write analysis on proven data and research. They may feel that with proven research they are confident enough to work from it as compared to primary research they don’t have an exact starting point and must come up with something original. I think that scientists believe that being acquainted with the same researched genes amongst themselves can bring up a miraculous discovery or a solution because many professionals are working on it together. This actually seems to be a very sensible method of Pharmocogenetics but I for one would hate to think that scientists are lazy and feeding off each other as there needs to be “something new” for pharmocogenetics to develop and progress. Isn’t this “excitement” surrounding Pharmocogenetics all about trying to find something that works? Instead of repeating the same material isn’t it supposed to discover something new to make personalized medicine work?
A clinical study is considered a “primary Pharmocogenetic study” when it meets the standardizations and states the aims of the abstract that the intention of the study was to investigate the gene variation on drug response. If not stated in the abstract as the purpose then it would be considered a secondary pharmocogenetic study instead. A primary pharmocogenetic is also as it sounds like, “primary research” which requires results with conducted experiments other than European and non-European specimens and with intended and unintended effects.
Page 12 refers to bettering the pharmocogenetics field as stated above by spending more time on primary research on more various genes and drugs. It also refers to means of bettering analysis with different metrics and techniques for good results. These results need to be efficient for cost-effectiveness as research isn’t inexpensive. Having precise and good quality results will increase cost-effectiveness for scientists and researchers as they will have a more firm grasp on pathology and gene variations so that they won’t waste money on unnecessary research. More reliable information is emerging because with better research techniques and primary results, they provide with new insights into predictive tests for diseases.
The “Recommendations for Future Research in Pharmacogenetics” plots out potential methods of improving Pharmacogenetics research. They mention bettering techniques, increasing sample size and broader research. One recommendation by the author as to: “Encouraging reporting null findings from high-quality studies” means to publish unexpected results as well as expected results to give chance for future findings because they might be useful at some point of other research as all results are meant to be observed and learned from to better the procedure the next time around. For example it seems that “The most frequently investigated disease areas were cancer (456 studies; 27.3%), neurology/psychiatry (321 studies; 19.2%) and cardiovascular disease (287 studies; 17.2%)” and only one-eighth of studies (210, 12.6%) examined adverse drug effects. If scientists would report null findings on studies on adverse drug effects as well as they do on cancer and cardiovascular diseases there can be more effort and interest to examine ignored studies as well.