Practice Of Off-label Prescribing Research Articles

The Law and Practice of Off-Label Prescribing and Physician Promotion.

Prescription of medications for off-label indications is an increasingly common practice; recent events highlight such prescribing as one of the cornerstones of evolving clinical treatment. Clinicians are afforded substantial deference in prescribing practices and other treatments falling within the realm of the actual practice of medicine, including prescribing for off-label indications. Yet clinicians are not necessarily free to promote a medication for the same off-label indication they may have just prescribed for a patient. While trends in jurisprudence appear to be favoring clinicians' freedom to promote prescription medication for any use, in a majority of jurisdictions, the U.S. government can still bring considerable weight to bear on clinicians promoting off-label uses of prescription medications. We review the relevant laws and regulations pertaining to off-label prescription and promotion, as well as the possible legal consequences. The regulations pertaining to physician and pharmaceutical manufacturers regarding off-label drug use are complex. Suggestions are provided to help physicians better navigate the medical-legal landscape when prescribing or promoting medications for off-label use. Physician mindfulness to pertinent legal precedents will allow them to prescribe and promote medications with a higher level of critical reasoning to optimize care and reduce risk.

The practice of off label prescribing and associated adverse drug reactions in pediatric inpatients in a tertiary care hospital in India

Abstract Objectives To assess the extent of use, patterns, variables and Adverse Drug Reactions associated with off label prescribing in Pediatrics. Methods A prospective observational study was conducted for a period of 6 months for children of the age group 0-17 years in a tertiary care Hospital in Maharashtra, India. Off label drug use was assessed using Micromedex and British National Formulary for Children (BNFC 2016–2017). Adverse Drug Reactions (ADRs) were assessed according to the physicians' notes, recorded during the patient's hospital stay. Pearson correlation coefficient was computed to assess the relationship between age and the number of off-label drugs. Odds ratio was calculated for the occurrence of ADRs in on-label prescriptions Vs off label-prescriptions. A P value of <0.05 was considered as significant. Key findings A total of 1514 prescriptions were evaluated in 300 patients. Out of which 542 (35.79%) and 423 (27.9%) were off label according to Micromedex and BNFC respectively. The number of patients who received at least one off label was found to be 225 (75%) – Micromedex and 223 (74.3%) – BNFC Unspecified indication and use of drugs outside the specified age limit were identified as the main variables associated with off label prescribing. Highest proportion of off-label drugs was found in Alimentary system. A total of 35 ADRs (OR 6.92 CI 95%(OR 6.92, 95% CI, 3.13-15.27)) were identified in 31 patients. Conclusions Off-label drug use is prevalent in the pediatric population and warrants an evidence-based approach to improve prescribing practices in pediatrics.

Hospital pharmacists' perceived beliefs and responsibilities in indication-based off-label prescribing.

Background Off-label prescribing is prevalent in healthcare. There is a lack of understanding of pharmacists' attitudes toward the practice of off-label prescribing, especially those that are prescribed for other indications than approved ones (termed as indication-based off-label prescribing). Objective Explore hospital pharmacists' attitudes toward and perceived responsibility in off-label and indication-based off-label prescribing in hospital pharmacy practice. Setting Pharmacists practicing in hospitals in the United States were investigated. Method Pharmacists were contacted via email through State affiliates of the American Society of Health-System Pharmacist. The survey described an indication-based off-label medication order for a hospitalized patient and the prescribing physician. Data were collected via Qualtrics. Main outcome measure Questions focused on awareness, beliefs, and responsibility-including, risk assessment and monitoring outcomes-related to off-label and indication-based offlabel prescribing. Results Of 107 pharmacist respondents, about 79% and 98% reported being familiar with offlabel and indication-based off-label prescribing, respectively. While 77.6% pharmacists believed that patients should be informed, only 37.4% agreed that they had responsibility of informing physicians; presence of policy was associated (p<0.02) with pharmacist agreeing to inform physicians. Over 70% agreed that patients should be closely monitored for outcomes and 43.1% believed physicians had predominant responsibility of monitoring outcomes. Conclusion Pharmacists' perceived responsibility and beliefs regarding off-label prescribing are insightful that can be utilized for improving patient care.

The Pharmacokinetics of Second-Generation Long-Acting Injectable Antipsychotics: Limitations of Monograph Values.

Product monographs (also known by terms such as Summary of Product Characteristics and Highlights of Prescribing Information, depending on the jurisdiction) provide essential information to ensure the safe and effective use of a drug. Medical practitioners often rely on these monographs for guidance on matters related to pharmacokinetics as well as indications, contraindications, clinical pharmacology, and adverse reactions. The clinical and scientific information found within these documents, forming the basis for decision making, are presumed to be derived from well-designed studies. The objective of this review is to examine the source and validity of the pharmacokinetic data used in establishing the half-lives and times to steady-state reported in the product monographs of second-generation long-acting injectable antipsychotics. Thus, we have critically evaluated the clinical trials from which the pharmacokinetic parameters listed in the product monographs were determined. In many cases, the pharmacokinetic information presented in product monographs is of limited use to clinicians wishing to optimize the effectiveness and tolerability of second-generation long-acting injectable antipsychotics. Under such circumstances, off-label prescribing practices may actually produce better clinical outcomes than if decisions were made based on the product monographs alone.

New users of antipsychotic medication: A population-based cohort study of occupational outcome measures in relation to antipsychotic on-label and off-label prescribing practices

BackgroundTreatment with antipsychotic medication is thoroughly investigated in schizophrenia and bipolar disorder but is also widely applied for a diversity of off-label conditions, despite an uncertain risk-benefit ratio. This study examined the relationship between antipsychotic prescribing patterns and labor market affiliation, considering both authority approved and off-label prescriptions and the relation to polypharmacy. MethodsRegister-based cohort study using a dataset of 71,254 new antipsychotic users with a psychiatric diagnosis. Labor market affiliation and duration of welfare payments were analyzed using linear regression models and duration analysis. The analyses were adjusted for the following confounding variables: age, gender, diagnosis, marital status, length of education, and utilization of mental health care services. ResultsThe majority of new antipsychotic users received welfare payments for prolonged periods of time during the observation period, even more so for individuals treated with antipsychotic polypharmacy or other antipsychotic combination regimens. The risk of permanently leaving the labor market was also associated with antipsychotic combination regimen. ConclusionsAntipsychotic treatment, especially in combination with other antipsychotics or other psychotropic drugs, could serve as a marker of subjects with increased need for support to maintain the labor market affiliation. However, causality cannot be inferred from an observational study because of residual confounding that could not be adjusted for in this study.

Prescribing patterns of target-specific oral anticoagulants: an academic hospital perspective.

Target-specific oral anticoagulants have been rapidly adopted into clinical practice for stroke prophylaxis and venous thromboembolism treatment, raising concerns about off-label prescribing practices. We conducted a retrospective review of consecutive patients prescribed dabigatran, rivaroxaban or apixaban prior to inpatient hospitalization over an 18-month period to examine the off-label prescribing frequency, contraindications and related complications. Chart review included baseline demographics, hospital admitting service, outpatient prescribing service, renal function, therapeutic indication, echocardiographic findings, contraindications, major bleeding events and vital status. We identified 160 patients who received a target-specific oral anticoagulant prior to hospitalization. Over half (53.1%) of the patients received rivaroxaban, 43.7% received dabigatran and 3.1% received apixaban. Atrial fibrillation (68.1%) and venous thromboembolism treatment (25.6%) were the most common indications. Ninety percent of patients had a U.S. Foods and Drugs Administration (FDA)-approved indication for therapy. Major bleeding events occurred in 4.4% of patients. Cardiology was the most common prescribing and admitting service (43.8 and 31.3%), and more frequently adhered to FDA-approved indications (97 vs. 84%, P = 0.01). There were no significant differences between prescribing services regarding major contraindications (P = 0.14) and major bleeding events (P = 0.77). Off-label prescription rates for target-specific oral anticoagulants were infrequent and not associated with increased adverse events.

Enhancing postmarketing surveillance: continuing challenges.

In this issue, Zeitoun and colleagues 1 examined whether any relationship existed between the speed of European Medicines Agency (EMA) regulatory review of 161 medicines between 2001 and 2010 and reported postmarket safety events; they found no relevant correlation. Neither rapid EMA regulatory review nor approval near the deadline was associated with more reports of adverse events. The findings are reassuring, given the pressure that regulatory agencies face to achieve timely reviews and ensure public safety. There is evidence, however, that the rush to approve new medicines may compromise safety, at least in the United States. Since the approval process at the Food and Drug Administration (FDA) was accelerated through a legislative cost-shifting strategy known as the Prescription Drug User Fee Act in 1992, the numbers of both postmarketing black-box warning and market withdrawals have significantly increased 2. But the tensions affecting one regulatory system may not be applicable to another. The process of premarket approval should also be viewed as just one facet of pharmaceutical safety. While the findings of Zeitoun et al. 1 are encouraging, neither regulatory agencies nor the public should become complacent. Belated discovery of serious adverse drug events is not always the result of poorly conducted clinical trials, nefarious drug companies or weak regulatory oversight; some drug-related complications reflect the complexities of human biology. The most meticulous regulatory review will never guarantee the detection of all adverse drug effects. Maintaining a robust system of postmarketing surveillance must complement a thorough drug approval process. However, these processes too are often thwarted by limitations of health record data and corresponding decision support tools (e.g. dashboards, data cubes, etc.), and the practice of off-label prescribing.

Off-label prescriptions in diabetic foot

Prescription of a drug outside of the indications for which it was originally approved by regulators is internationally known as "off-label" prescription. We describe off-label treatments for the diabetic foot reported in international scientific literature. This is a qualitative and descriptive bibliographical review based on the results of a search of the Medline international database. The criteria for review were publication between January 1985 and November 2013, and the MeSH (Medical Subject Heading) keywords "off-label use" OR "off-label" OR "off-label prescribing" plus "diabetic foot" were input on the search form. Nine studies were selected that contained information about off-label treatments for the diabetic foot. We conclude that the practice of off-label prescribing has potential benefits. In some situations an off-label prescription is the only treatment available for patients, either because a more targeted drug does not exist, or because other methods of treatment are ineffective or unavailable due to patient intolerance.

Off-label treatment in diabetic retinopathy

&lt;p class="MsoNormal" style="margin-bottom: 0.0001pt; text-align: justify;"&gt;&lt;strong&gt;&lt;em&gt;&lt;span style="font-size: 8.0pt; font-family: Calibri-BoldItalic; mso-bidi-font-family: Calibri-BoldItalic; mso-ansi-language: EN-US;" lang="EN-US"&gt;Introduction: &lt;/span&gt;&lt;/em&gt;&lt;/strong&gt;&lt;em&gt;&lt;span style="font-size: 8.0pt; font-family: Calibri-Italic; mso-hansi-font-family: Calibri-BoldItalic; mso-bidi-font-family: Calibri-Italic; mso-ansi-language: EN-US;" lang="EN-US"&gt;The prescribing a drug without the indications for which the drug was originally approved by regulators is internationally known as prescribing “off-label”. &lt;/span&gt;&lt;/em&gt;&lt;strong&gt;&lt;em&gt;&lt;span style="font-size: 8.0pt; font-family: Calibri-BoldItalic; mso-bidi-font-family: Calibri-BoldItalic; mso-ansi-language: EN-US;" lang="EN-US"&gt;Objective&lt;/span&gt;&lt;/em&gt;&lt;/strong&gt;&lt;em&gt;&lt;span style="font-size: 8.0pt; font-family: Calibri-Italic; mso-hansi-font-family: Calibri-BoldItalic; mso-bidi-font-family: Calibri-Italic; mso-ansi-language: EN-US;" lang="EN-US"&gt;: To describe the off-label therapy in diabetic retinopathy, reported international scientific literature, through an integrative bibliographical review. &lt;/span&gt;&lt;/em&gt;&lt;strong&gt;&lt;em&gt;&lt;span style="font-size: 8.0pt; font-family: Calibri-BoldItalic; mso-bidi-font-family: Calibri-BoldItalic; mso-ansi-language: EN-US;" lang="EN-US"&gt;Method&lt;/span&gt;&lt;/em&gt;&lt;/strong&gt;&lt;em&gt;&lt;span style="font-size: 8.0pt; font-family: Calibri-Italic; mso-hansi-font-family: Calibri-BoldItalic; mso-bidi-font-family: Calibri-Italic; mso-ansi-language: EN-US;" lang="EN-US"&gt;: Integrative review by searching the Medline international database for review of manuscripts. &lt;/span&gt;&lt;/em&gt;&lt;strong&gt;&lt;em&gt;&lt;span style="font-size: 8.0pt; font-family: Calibri-BoldItalic; mso-bidi-font-family: Calibri-BoldItalic; mso-ansi-language: EN-US;" lang="EN-US"&gt;Results&lt;/span&gt;&lt;/em&gt;&lt;/strong&gt;&lt;em&gt;&lt;span style="font-size: 8.0pt; font-family: Calibri-Italic; mso-hansi-font-family: Calibri-BoldItalic; mso-bidi-font-family: Calibri-Italic; mso-ansi-language: EN-US;" lang="EN-US"&gt;: A total 852 scientific productions were identified, and 37 studies were selected by contain information about the off-label therapy in diabetic retinopathy. &lt;/span&gt;&lt;/em&gt;&lt;strong&gt;&lt;em&gt;&lt;span style="font-size: 8.0pt; font-family: Calibri-BoldItalic; mso-bidi-font-family: Calibri-BoldItalic; mso-ansi-language: EN-US;" lang="EN-US"&gt;Conclusion&lt;/span&gt;&lt;/em&gt;&lt;/strong&gt;&lt;em&gt;&lt;span style="font-size: 8.0pt; font-family: Calibri-Italic; mso-hansi-font-family: Calibri-BoldItalic; mso-bidi-font-family: Calibri-Italic; mso-ansi-language: EN-US;" lang="EN-US"&gt;: The practice of off-label prescribing in diabetic retinopathy has benefits, and in some situations is the only treatment available.&lt;/span&gt;&lt;/em&gt;&lt;/p&gt;

Off-Label Prescribing in Older Patients

The practice of off-label prescribing, i.e. prescribing drugs either for unregistered/unapproved therapeutic indications and age groups or using unregistered/unapproved doses or methods of administration, is common in older patients. This may be due to the poor representation of this group in pre-marketing clinical trials assessing therapeutic efficacy and safety of novel therapies or merely to the fact that trials in a particular indication have not been undertaken. Off-label prescribing should not be viewed as scientifically or ethically unsound when there are good clinical data to support a particular therapeutic indication. However, a number of steps should be followed in order to ensure therapeutic efficacy, reducing, at the same time, the risk of adverse drug reactions and/or medical litigation. This article discusses the current epidemiology and trends in off-label prescribing in older patients, the scientific and ethical justification of this practice, medico-legal implications, and proposed strategies for risk mitigation.

Off-label chemotherapy use in a military treatment facility

6631 Background: Off-label prescribing of chemotherapeutics is thought to be frequent but scant data exist to quantify its occurrence. The few studies evaluating off-label drug use in oncology show that the frequency ranges from 6.7% to 75%. This is the first known evaluation of oncology prescribing practices in a military treatment facility. Methods: After approval by the institutional review board, all outpatient chemotherapy orders from 2006 given in our clinic were reviewed. The date, drug name, dose, diagnosis, intention of therapy (curative, adjuvant, or palliative), and provider status (staff or fellow) were entered into an Excel spreadsheet. Package inserts for each drug were reviewed to determine if the medication was given on- or off-label. The dates of approval and label updates were further defined from FDA press releases. The percentage of courses and individual doses given off-label were calculated. Results: 186 patient charts were included in the analysis. Of 1,341 courses of chemotherapy, 50.48 % (n = 677) were given off-label. Of 3,299 doses of chemotherapy, 47.9% (1,581) were given off-label. Of the drugs prescribed, the most frequently dosed off-label were fluorouracil (n = 334), capecitabine (n = 229), traztuzumab (n = 123), leucovorin (n = 119), and carboplatin (n = 112). Of the 1,581 doses given off-label, 49% (n = 779) were given adjuvantly, 34% (n = 543) were given palliatively, and 16% (n = 259) were given curatively. Conclusions: Based on the current FDA labeling of chemotherapeutics, nearly half of the doses given in our outpatient clinic were off-label. However, the vast majority of our off-label use, such as adjuvant fluorouracil-based therapy, is considered standard of care and is supported by National Comprehensive Cancer Network practice guidelines and compendium listings. This retrospective analysis adds to the scant literature regarding off-label prescribing practices in oncology. No significant financial relationships to disclose.

Unapproved prescription practices in primary pediatric clinics in Israel: A prospective analysis

Background: Many medications have not been approved for children because of a lack of data that can ensure acceptable standards of safety, efficacy, and optimal dose. Objective: The purpose of this study was to determine the extent of unlicensed and off-label medications used in primary pediatric clinics in Israel. Methods: This study was a prospective analysis of medications prescribed during consecutive clinic visits to children from different ethnic communities and different regions of Israel, during different seasons of the year. Pediatricians completed forms with patient and medication data for each patient visit included in the study. The product licenses for age, dose, indication, and route of administration of medications prescribed to children aged <18 years were compared. Results: The study was carried out in the clinical practices of 6 board-certified pediatricians treating a total of ∼9300 children in 2000–2001. A total of 1925 prescriptions for 160 different medications were given to 1802 children (959 boys, 843 girls, mean [SD] age, 4.8 [3.9] years). Of the 298 (15.5%) of unapproved prescriptions given, 1 (0.3%) was for an unlicensed medication, and 297 (99.7%) were given in an off-label manner to 280 children (15.5%). Antibiotic and antiashmatic agents were the most frequently prescribed off-label medications. Infants received more unapproved medications than did children ( P < 0.001), and children, more than did adolescents ( P < 0.001). Statistical analysis did not reveal significant ethnic or seasonal differences in off-label prescribing practices. Conclusions: Based on the results of the present survey, many medications prescribed to children have not passed the licensing process as exists for adults. A large number of children in primary pediatric clinics in Israel as well as in other countries receive a myriad of unapproved medication, prescriptions.