9 research outputs found

    The Prevalence and Cost of Unapproved Uses of Top-Selling Orphan Drugs

    Get PDF
    Introduction: The Orphan Drug Act encourages drug development for rare conditions. However, some orphan drugs become top sellers for unclear reasons. We sought to evaluate the extent and cost of approved and unapproved uses of orphan drugs with the highest unit sales. Methods We assessed prescription patterns for four top-selling orphan drugs: lidocaine patch (Lidoderm) approved for post-herpetic neuralgia, modafinil (Provigil) approved for narcolepsy, cinacalcet (Sensipar) approved for hypercalcemia of parathyroid carcinoma, and imatinib (Gleevec) approved for chronic myelogenous leukemia and gastrointestinal stromal tumor. We pooled patient-specific diagnosis and prescription data from two large US state pharmaceutical benefit programs for the elderly. We analyzed the number of new and total patients using each drug and patterns of reimbursement for approved and unapproved uses. For lidocaine patch, we subcategorized approved prescriptions into two subtypes of unapproved uses: neuropathic pain, for which some evidence of efficacy exists, and non-neuropathic pain. Results: We found that prescriptions for lidocaine patch, modafinil, and cinacalcet associated with non-orphan diagnoses rose at substantially higher rates (average monthly increases in number of patients of 14.6, 1.45, and 1.58) than prescriptions associated with their orphan diagnoses (3.12, 0.24, and 0.03, respectively (p75%). Increases in lidocaine patch use for non-neuropathic pain far exceeded neuropathic pain (10.2 vs. 3.6 patients, p<0.001). Discussion In our sample, three of four top-selling orphan drugs were used more commonly for non-orphan indications. These orphan drugs treated common clinical symptoms (pain and fatigue) or laboratory abnormalities. We should continue to monitor orphan drug use after approval to identify products that come to be widely used for non-FDA approved indications, particularly those without adequate evidence of efficacy

    Multicenter external validation and comparison of stone scoring systems in predicting outcomes after percutaneous nephrolithotomy

    No full text
    Background and Purpose: Several scoring systems have recently emerged to predict stone-free rate (SFR) and complications after percutaneous nephrolithotomy (PCNL). We aimed to compare the most commonly used scoring systems (Guy's stone score, S.T.O.N.E. nephrolithometry, and CROES nomogram), assess their predictive accuracy for SFR and other postoperative variables, and develop a risk group stratification based on these scoring systems. Materials and Methods: We performed a retrospective review of patients who have had a PCNL at four academic institutions between 2006 and 2013. Primary outcome was SFR within 3 weeks of the surgery and secondary outcomes were operative time (OT), complications, and length of stay (LOS). We performed chi-squared, t-test, logistic, linear, and Poisson regressions, as well as receiver operating characteristics curve with area under the curve (AUC) calculation. Results: We identified 586 patients eligible for analysis. Of these, 67.4% were stone free. Guy's, S.T.O.N.E., and CROES score were predictive of SFR on multivariable logistic regression (odds ratio [OR]: 1.398, 95% confidence interval [CI]: 1.056, 1.852, p=0.019; OR: 1.417, 85% CI: 1.231, 1.631, p<0.001; OR: 0.993, 95% CI: 0.988, 0.998, p=0.004) and have similar predictive accuracy with AUCs of 0.629, 0.671, and 0.646, respectively. On multivariable linear regression, only S.T.O.N.E. was an independent predictor of longer OT (=14.556, 95% CI: 12.453, 16.660, p<0.001). None of the scores were independent predictors of postoperative complications or a longer LOS. Poisson regression allowed for risk group stratification and showed the S.T.O.N.E. score and CROES nomogram to have the most distinct risk groups. Conclusions: The three evaluated scoring systems have similar predictive accuracy of SFR. S.T.O.N.E. has additional value in predicting OT. Risk group stratification can be used for patient counseling. Further research is needed to identify whether or not any is superior to the others with regard to clinical usefulness and predictive accuracy

    Evidence-Based Clinical Practice Guidelines for Laser-Assisted Drug Delivery.

    No full text
    ImportanceLaser-assisted drug delivery (LADD) is used for various medical and cosmetic applications. However, there is insufficient evidence-based guidance to assist clinicians performing LADD.ObjectiveTo develop recommendations for the safe and effective use of LADD.Evidence reviewA systematic literature review of Cochrane Central Register of Controlled Trials, Embase, and MEDLINE was conducted in December 2019 to identify publications reporting research on LADD. A multidisciplinary panel was convened to draft recommendations informed by the systematic review; they were refined through 2 rounds of Delphi survey, 2 consensus meetings, and iterative review by all panelists until unanimous consensus was achieved.FindingsOf the 48 published studies of ablative fractional LADD that met inclusion criteria, 4 were cosmetic studies; 21, oncologic; and 23, medical (not cosmetic/oncologic), and 6 publications of nonablative fractional LADD were included at the request of the expert panel, producing a total of 54 studies. Thirty-four studies (63.0%) were deemed to have low risk of bias, 17 studies (31.5%) had moderate risk, and 3 (5.5%) had serious risk. The key findings that informed the guidelines developed by the expert panel were as follows: LADD is safe in adults and adolescents (≥12 years) with all Fitzpatrick skin types and in patients with immunosuppression; it is an effective treatment for actinic keratosis, cutaneous squamous cell carcinoma in situ, actinic cheilitis, hypertrophic scars, and keloids; it is useful for epidermal and dermal analgesia; drug delivery may be increased through the application of heat, pressure, or occlusion, or by using an aqueous drug solution; laser settings should be selected to ensure that channel diameter is greater than the delivered molecule; antibiotic prophylaxis is not recommended, except with impaired wound healing; antiviral prophylaxis is recommended when treating the face and genitalia; and antifungal prophylaxis is not recommended. The guideline's 15 recommendations address 5 areas of LADD use: (I) indications and contraindications; (II) parameters to report; (III) optimization of drug delivery; (IV) safety considerations; and (V) prophylaxis for bacterial, viral, and fungal infections.Conclusions and relevanceThis systematic review and Delphi consensus approach culminated in an evidence-based clinical practice guideline for safe and effective use of LADD in a variety of applications. Future research will further improve our understanding of this novel treatment technique
    corecore