Identifying Conflicting Clinical Variant Essay
Identifying Conflicting Clinical Variant Essay
Genetic variation is a term that describes the variation in the DNA sequencing inour genomes. In genetic diagnosis, classification of the variant forms the basis for clinical perception. Variant classification is sequenced based testing of the germ-line DNA to determine whether an individual carries a variation in an allele that is likely to cause a problem in normal gene function. Identifying Conflicting Clinical Variant Essay. There are international guidelines and principles that are available for variant classification, but despite all these guideline interpretation, there is a significant difference in the classification of genetic variants which leads to inappropriate medical management. A wrong classification can misguide the clinical judgment which includes severe consequences in risk compartmentalization among the family members.
Variants that have clinical conflicting classification cause uncertaininterpretation whether the variant has an impact on the disease of a given patient. Thus, to overcome this specified problem we can implement machine learning to genomics through which we can predict whether the variant will have a conflicting clinical classification that could help the patient to take measures so as to prevent or cure a particular disease.
The dataset that is used for this analysis is collected from ClinVar and Kaggle. The dataset has a binary representation, i.e. 0 denotes consistent classification whereas 1 denotes conflicting classification.
To predict whether a variant will have conflicting clinical classification we can implement a supervised machine learning method i.e. classification technique. Classification technique is used to classify the data into various classes according to constraints. By applying classification technique we can categorize whether the variant is concordant variant or conflictingvariant. For this analysis we can use various tools such as Python, R or Weka in which we can run different classification algorithms like the k-nearest neighbor, Naive Bayes, SVM etc. to obtain the accurate result.
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Relationships between physicians and biomedical researchers on the one hand and pharmaceutical, medical device, and biotechnology companies on the other hand are widespread and have produced important benefits, particularly in the development of new tests and treatments. At the same time, these relationships have also created significant risks that the financial goals of industry may conflict with the professional goals of medicine. The goals of for-profit medical companies are to produce products that improve health and, at the same time, to ensure a financial return to shareholders. The primary goals of medicine include improving health by providing beneficial care to patients, conducting valid research, and offering excellent medical education. In pursuing those goals, individual professionals, health care institutions, and research organizations have obligations to put patient interests first, carry out unbiased research, critically appraise information, and serve as role models of professional behavior for students. The problem of conflict of interest arises because in some circumstances in modern medicine these goals and obligations are at risk of being compromised by the undue pursuit of financial gain or other secondary interests . Identifying Conflicting Clinical Variant Essay.
Medicine today faces many difficult challenges, including, among others, high costs of treatment and associated pressures to cut costs, lack of availability of health insurance, and persistent medical errors. In comparison, the problem of conflict of interest may seem less significant. However, none of the other challenges can be adequately met if conflicts of interest are not well managed. For example, patients and the public need to be able to trust that the high costs of health care and health insurance arise from the provision of services that are beneficial, necessary, appropriately priced, and not inappropriately driven by the financial interests of physicians, other health care providers, or medical product companies. Failure to deal with the problem of conflict of interest can undermine efforts to address the other serious challenges that medical professionals and researchers face today.
This chapter develops a conceptual framework for identifying and assessing conflicts of interests.1In addition to defining the concept of conflict of interest and clarifying some common misunderstandings about its applications, the chapter presents principles to guide the formulation and implementation of conflict of interest policies. The principles take the form of (1) statements of the purposes of conflict of interest policies, (2) criteria for assessing the content of these policies, and (3) criteria for evaluating the implementation of policies. The principles do not directly yield decisions in particular cases or even rules that could be directly enforced, nor do they determine in advance the relative importance of all the values involved in making decisions. In applying them to particular policies and individual cases, there is no substitute for judicious practical judgment sensitive to the institutional context. However, the principles provide an essential framework for formulating and implementing any conflict of interest policy. They focus attention on the most important factors that should be considered when professionals and institutions make decisions and policies regarding conflicts of interest, select the agents who should be responsible for implementing and enforcing those policies, and choose the methods that they will use to regulate conflicts of interest. Identifying Conflicting Clinical Variant Essay.
WHAT IS A CONFLICT OF INTEREST?
Although conflict of interest policies are now widespread in many areas of medicine, the meaning and purposes of these policies are not always clearly understood. The term “conflict of interest” is used in many different and often inconsistent ways. Nonetheless, institutional and public policies on conflicts of interest need to define what the policies cover and what they do not cover.
The definition that the committee adopted is consistent with the core meaning of the concept as it is used in many institutional policies. It is, however, formulated to clarify key elements that are sometimes obscured in discussions of those policies.
A conflict of interest is a set of circumstances that creates a risk that professional judgment or actions regarding a primary interest will be unduly influenced by a secondary interest.
To avoid common misunderstandings of the concept that can lead to misplaced and ultimately ineffective or counterproductive policies, the committee stresses the importance of each of the three main elements of a conflict of interest: the primary interest, the secondary interest, and the conflict itself.
The primary interest that conflict of interest policies seek to protect varies according to the purpose of a professional activity. Primary interests include promoting and protecting the integrity of research, the welfare of patients, and the quality of medical education. Physicians and medical researchers accept the primacy of these interests when they act in their professional roles. Physicians and researchers exercise judgment and discretion in their work. Patients, the public, research participants, medical students, residents, and fellows need to trust physicians and researchers to act and make judgments in ways that are consistent with these primary interests.Identifying Conflicting Clinical Variant Essay. These primary interests are sometimes stated as ends or goals (e.g., promoting patient welfare), as obligations (e.g., the physician’s obligation to promote patient welfare), or as rights (e.g., the patient’s right to have the doctor promote his or her welfare). The committee uses the term primary “interests” to encompass all of these values, however they are stated. Whatever the primary interests are, the point of regulating conflicts of interest is to try to ensure that secondary interests do not subvert physicians’ and researchers’ decisions and actions regarding those primary interests and do not undermine trust in their clinical or scientific judgment. Furthermore, medical institutions—including medical schools, research institutes, professional societies, scientific journals, patient advocacy organizations, or government health agencies—should also keep these primary interests paramount, as discussed further in Chapter 8.
To be sure, identification of the exact primary interest in specific situations may sometimes be challenging, and primary interests sometimes conflict with each other. For example, in public health emergencies or under conditions of dire resource scarcity, physicians may have fundamental obligations to the population as a whole that may compete with their obligations to individual patients. In clinical research, the welfare of the participants in a study and the study’s successful completion may be in conflict. Nonetheless, it is almost always clear that a primary interest should take precedence over a secondary interest.
The second main element of a conflict of interest is the secondary interest. Secondary interests may include not only financial gain but also the desire for professional advancement, recognition for personal achievement, and favors to friends and family or to students and colleagues. Conflict of interest policies typically and reasonably focus on financial gain and financial relationships. The reason is not that financial gains are necessarily more corrupting than the other interests but that they are relatively more objective, fungible, and quantifiable. A financial interest therefore tends to be more effectively and fairly regulated than other secondary interests. Furthermore, for-profit companies exert influence primarily through their financial relationships with physicians and researchers. They cannot bestow professional rewards such as prestigious scientific prizes that may also lead to conflicts of interest.
Most secondary interests, including financial interests, are—within limits—legitimate and even desirable goals. The secondary interests are objectionable only when they have greater weight than the primary interest in professional decision making. For example, for a researcher or a teacher, financial interests should be subordinate to presenting scientific evidence in an unbiased manner in publications and presentations. Identifying Conflicting Clinical Variant Essay.
A financial interest does not have to be great for the influence to be undue. Indeed, social science research suggests that gifts of small value may influence decisions (see Appendix D). It also suggests that influence may operate without an individual being conscious of it. When a secondary interest has inappropriate weight in a decision and distorts the pursuit of a primary interest, it is exerting undue influence.
The third key element of the definition is the conflict itself. It is not an occurrence in which primary interests are necessarily compromised but, rather, a set of circumstances or relationships that create or increase the risk that the primary interests will be neglected as a result of the pursuit of secondary interests. A conflict of interest exists whether or not a particular individual or institution is actually influenced by the secondary interest. The claim that a conflict of interest exists is based on common experience and social science research. Both experience and research indicate that under certain conditions there is a risk that professional judgment may be influenced more by secondary interests than by primary interests.
Some of these elements of a conflict of interest refer to degrees or quantities (e.g., more or less influence), but they are not directly quantifiable. What counts as undue is a matter of judgment and depends on the context. It is not a numerical probability but a judgment in a particular situation about whether a risk is undue or inappropriate. The standards for making such a judgment should be transparent and clearly specified in actual policies rather than in vague statements that professionals should avoid “undue influence.” Subsequent chapters examine what situations or relationships may be considered inappropriate in research, patient care, medical education, and practice guideline development. Appendix C offers perspectives on conflicts of interest in other professions.
Conflicts of interest should be distinguished from other closely related conflicts. Not all conflicts in medicine are conflicts between a primary and a secondary interest. A conflict of obligation arises when an individual or institution has duties that require different actions but only one of these actions can be taken in the given circumstance. Dilemmas in medical ethics often take this form, that is, the need to make hard choices between two values, neither one of which is clearly superior to the other. A common example is maintaining the confidentiality of a patient with a contagious disease, which may conflict with preventing that patient from harming someone else. Identifying Conflicting Clinical Variant Essay. There is no conflict of interest in this example because both interests have plausible claims to be considered primary. Conflicts of obligation are essentially conflicts among different primary interests. Both obligations or interests are legitimate, often equally so, and it cannot be said in advance which one should take priority.
Conflicts of commitment are closer to conflicts of interest. They often involve a conflict between what institutions view as employees’ primary responsibilities to the institution and the employees’ outside commitments, such as voluntary community service, participation in a political campaign, or teaching or conducting research for another institution. Like conflicts between primary interests, conflicts of commitment involve two perfectly respectable activities (indeed, in some cases, identical activities, except that they are conducted at different institutions). Also, like conflicts of interest, the institution can legitimately claim in advance that one activity takes priority over the other if they come into conflict in any way. The concern is not usually about the risk of undue influence over specific decisions (e.g., the prescribing of a particular medication or the reporting of research findings). Rather, the concern is about time and effort, for example, whether individuals are devoting sufficient attention to their responsibilities within their own primary institution. Conflicts of interest and conflicts of commitment are sometimes covered in the same institutional policy; but the circumstances, risks, and evaluative frameworks are sufficiently different that they warrant separate consideration. Nevertheless, it makes sense for the policies to be covered in the same documents and information resources and to be administered by the same officials and committees.
WHAT ARE THE PURPOSES OF CONFLICT OF INTEREST POLICIES?
Institutions, professional organizations, and governments establish policies to address the problem of conflict of interest on behalf of the public. Conflict of interest policies are attempts to ensure that professional decisions are made on the basis of primary interests and not secondary interests. (See the discussion of the policies of other professions in Appendix C.) As discussed further in Chapter 9, such policies work best when they are preventive and corrective rather than punitive. To the extent that they are effective, they serve two overarching purposes: maintaining the integrity of professional judgment and sustaining public confidence in that judgment. That professionals should promote these purposes constitutes the fundamental principle underlying any respectable conflict of interest policy.
First, the most obvious way in which the integrity of professional judgment can be compromised is through bias. Other practices can also undermine that integrity when they violate standards of professional conduct, such as the failure to publish research findings in a timely manner, the failure to treat students and postdoctoral fellows fairly, and a lack of openness with patients. Conflict of interest policies seek to minimize the influence of secondary interests in all these practices. They most significantly guard against the risk that financial interests will have excessive weight in decisions about the conduct of research, teaching, the provision of patient care, and the development of practice guidelines.
Such policies do not assume that any particular professional will necessarily let financial gain influence his or her judgment, nor do they imply that the individual researcher or physician is an unethical person.Identifying Conflicting Clinical Variant Essay. They assume only that under some conditions a risk exists that the decisions may be unduly influenced by considerations that should be irrelevant. Nonetheless, physicians and researchers are sometimes offended by assertions that they have conflicts of interest, believing that such assertions impugn their ethical integrity.
To avoid what they believe to be the negative connotations of “conflict of interest,” some institutions use such phrases as “relationships with industry” or “financial relationships” to describe not only relationships that may be evaluated for the presence of potential conflicts but also relationships that are judged to be conflicts of interest. This less direct language has the effect of obscuring the serious risks that conflicts pose. Such language is not necessary if it is recognized that the determination that an individual or institution has a conflict of interest is a judgment about the situation and not about the professional who happens to be in that situation.
The second purpose of conflict of interest policies—to help sustain public confidence in professional judgment—is less appreciated but no less important. Here the goal is to minimize conditions that would cause reasonable individuals to suspect that professional judgment has been improperly influenced by secondary interests, whether or not it has. The public includes not only patients and research subjects but also editorial writers and journalists, officials at nonprofit foundations, public officials, and other opinion leaders. When or if the public and public officials distrust physicians, researchers, or educators, they are likely to seek greater government regulation, withhold funding, and take other steps that could jeopardize future programs of patient care, research, or education.
When a physician, researcher, or educator acts in ways that lead to distrust, the consequences may affect colleagues, patients, students, and the institution or profession as a whole. Similarly, institutional practices can be the source of distrust, and the effects of such distrust may be even more widespread and damaging than distrust of an individual. Physicians retain a high standing with the public compared with the standing of many other professional groups; but physicians should be vigilant, because once public confidence is undermined, it may be difficult to restore.
As discussed in Appendix C, other professions—law, accounting, engineering, and architecture—have also recognized the importance of conflict of interest policies and ethical codes to promote objectivity in decision making and sustain public confidence. In some recent cases, most notably, accounting, failure to adhere to these codes has led to increased government regulation. Identifying Conflicting Clinical Variant Essay.
WHY NOT EXAMINE THE MOTIVES OF THE DECISION MAKER OR THE VALIDITY OF THE DECISION?
Individuals accused of having a conflict of interest often say that they would never let financial interests influence their decisions. This objection to conflict of interest policies misses the point. Because (as noted above) the conflict is a set of circumstances or conditions involving a risk rather than a specific individual decision, the existence of a conflict of interest does not imply that any individual is improperly motivated. Nevertheless, an individual professional might still object that it is not fair to generalize in this way. He or she may want to say: “Look at my actual decisions and consider my distinguished reputation.” However, conflict of interest policies are by their nature designed to avoid the need to investigate individual cases in this way. For at least two reasons, such policies do not focus on the motives in a particular case.
First, reliably ascertaining or inferring motives in this context is usually impossible for those assessing whether a relationship constitutes a conflict of interest. Generally, medical research, patient care, and education involve multiple considerations and many small judgments and decisions that are impractical to review; and even if they were reviewed, they would likely not yield a clear picture of the underlying motivation. Thus, readers of journal articles, medical students, patients, and conflict of interest committees are not in a good position to judge whether secondary interests motivated a decision. The motives behind institutional decisions are usually even more opaque.
Second, any thorough effort to determine motivation in a particular case would be improperly intrusive and highly time-consuming. Identifying Conflicting Clinical Variant Essay. Fair hearings could not be held and reliable conclusions could not be reached without risking violation of the rights of privacy of the many individuals who might be involved and without distracting many people from other important work.
Sometimes another, closely related objection to a claim that an individual has a conflict of interest is raised. This objection accepts that motives should not be considered but denies the relevance of the conditions under which decisions are made: “Judge my decision—the results of the research, the content of the lecture, the prescription of the drug—and not my financial interests.” Here again the problem is that many people affected by professional decisions are not in a position to judge the validity of those decisions. In addition, those who are competent to judge may not be able to do so until after the damage has occurred. Furthermore, the argument for judging outcomes ignores one of the two main purposes of conflict of interest policies: the maintenance of public confidence. Even valid decisions and research may not be widely accepted as such if they occur under conditions in which secondary interests are prominent. Moreover, many decisions in research and clinical care are close calls. Plausible reasons can be cited for each of several alternative choices. The decisive factor in whether a judgment or an action is accepted as valid may turn on whether a researcher or a clinician can be trusted to be acting for the sake of scientific truth and the best interests of patients.
Because it is both intrusive and usually impracticable to investigate motives and because the competent and timely appraisal of decisions is often difficult, it may be tempting to conclude that patients, the public, and researchers simply need to trust physicians. Trust is important, but generalized trust and reliance that medical professionals act in accord with primary professional interests may be difficult to maintain in the face of evidence that this trust is sometimes abused. Furthermore, creating trust in medical professionals who conduct research or develop practice guidelines is hard because they have little or no contact with many of the people who are affected by their decisions and who have only limited knowledge with which to evaluate the decisions. Trust is necessary and desirable, but it must be based on reasonable expectations. Those who rely on professionals must have good reason to trust their decisions. In short, they need assurance that the professionals are trustworthy. Policies designed to reduce conflicts of interest and mitigate their impact provide an important foundation for public confidence in medical professionals and institutions.Identifying Conflicting Clinical Variant Essay.
SHOULD POLICIES ALSO REQUIRE THAT PROFESSIONALS AVOID THE “APPEARANCE OF CONFLICT OF INTEREST”?
Some conflict of interest policies refer to actual or perceived conflicts of interest and state that professionals should avoid “even the appearance of a conflict of interest.” That requirement may lead to confusion. All conflicts of interest involve perceptions or appearances because they are specified from the perspective of people who do not have sufficient information with which to assess the actual motives of a decision maker and the effects of those motives on the decisions themselves.
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Policies that contrast actual and perceived conflicts of interest give rise to two problems. First, the contrast suggests that there is no conflict (only an appearance of a conflict) unless the decision maker actually favors secondary interests over primary interests. The implication, then, is that conflict of interest policies should treat a perceived conflict as less serious than an actual conflict. However, when a professional’s judgment is actually distorted by the acceptance of a gift or the prospect of influencing a stock in which the professional has an interest, the violation is no longer principally a conflict of interest but becomes a different kind of offense, one that may involve malpractice, scientific misconduct, or kickbacks.Identifying Conflicting Clinical Variant Essay. Those violations call for the use of procedures quite different from those on which conflict of interest policies should concentrate.
Second, the creation of a category of perceived conflicts, as distinct from actual conflicts, opens the door to overly broad and excessively subjective rules. If perceived conflicts are treated as different from the other (so-called actual) conflicts that the policy regulates, conduct that is perfectly proper can be unfairly called into question. With a loose notion of the perception or the appearance of a conflict of interest, circumstances that are suspicious only to uninformed people or predisposed reporters can be the basis of indiscriminate charges of conflicts of interest. Charges of conflicts of interest should be limited to circumstances specified by policies that are objectively grounded in past experience and reasonably interpreted on the basis of relevant and accessible information. Identifying Conflicting Clinical Variant Essay.
