Rahul Sasane

Increasing Patient Involvement in Drug Development

BACKGROUND To ensure the creation of treatments that maximize value at the lowest cost, all aspects of the health care system need to align with patient needs and preferences. Despite growing efforts to engage patients in research and regulatory activities, the pharmaceutical industry has yet to maximize patient involvement in the drug development process. OBJECTIVE To gain a better understanding of the present state of patient involvement in drug development. METHODS Through a semistructured interview methodology, we sought to identify opportunities, barriers, and examples of patient involvement in the drug development process. Telephone interviews were conducted with six senior leaders of evidence generation within the pharmaceutical industry and four patients. These interviews were supplemented with interviews with a research funder, a regulator, a patient advocacy group, and a caregiver. RESULTS Although our interviewees spoke of the potential benefits of aligning research around the needs of patients, there were few examples they could share to suggest this was occurring at scale. A number of barriers were identified including the added burden associated with adverse event reporting, concerns about patient representativeness or their ability to participate in drug development conversations, and the costs in time and resources involved relative to returns on investment. CONCLUSIONS As health care systems continue to evolve and establish patients as the primary stakeholder in their health care decision making, the pharmaceutical industry will need to be innovative to demonstrate the value of their products relative to the outcomes experienced by patients. Pharmaceutical companies should recognize the value of involving patients across the entire product life cycle and work to transform present perceptions and practices throughout their organizations.

The natural history of brain volume loss among patients with multiple sclerosis: A systematic literature review and meta-analysis

BACKGROUND Multiple sclerosis has been associated with progressive brain volume loss. OBJECTIVE We aimed to systematically summarize reported rates of brain volume loss in multiple sclerosis and explore associations between brain volume loss and markers of disease severity. METHODS A systematic literature search (2003-2013) was conducted to identify studies with ≥12months of follow-up, reported brain volume measurement algorithms, and changes in brain volume. Meta-analysis random-effects models were applied. Associations between brain volume change, changes in lesion volume and disease duration were examined in pre-specified meta-regression models. RESULTS We identified 38 studies. For the meta-analysis, 12 studies that reported annualized percentage brain volume change (PBVC), specified first-generation disease-modifying treatments (e.g., interferon-beta or glatiramer acetate) and used Structural Image Evaluation of Normalized Atrophy algorithm were analyzed. The annualized PBVC ranged from -1.34% to -0.46% per year. The pooled PBVC was -0.69% (95% CI=-0.87% to -0.50%) in study arms receiving first-generation disease-modifying treatments (N=6 studies) and -0.71% (95% CI=-0.81% to -0.61%) in untreated study arms (N=6 studies). CONCLUSIONS In this study, the average multiple sclerosis patient receiving first-generation disease-modifying treatment or no disease-modifying treatment lost approximately 0.7% of brain volume/year, well above rates associated with normal aging (0.1%-0.3% of brain volume/year).

Preferred Features of Oral Treatments and Predictors of Non-Adherence: Two Web-Based Choice Experiments in Multiple Sclerosis Patients

Background Oral disease modifying therapies (DMTs) for multiple sclerosis (MS) differ in efficacy, tolerability, and safety. Objective We sought to understand how these attributes impact patient preference and predicted DMT non-adherence among oral-naïve MS patients. Methods Adult MS patients from the “PatientsLikeMe” Web-based health data-sharing platform completed a discrete choice exercise where they were asked to express their preference for one of three hypothetical oral DMTs, each with a certain combination of levels of tested attributes. Another Web-based exercise tested a number of possible drivers of non-adherence, mainly side effects. Data from an MS clinic were used to adjust for sample bias. Respondents’ preferences were analyzed using Hierarchical Bayesian estimation. Results A total of 319 patients completed all questions. Most respondents were female (77.7%, 248/319) with mean age 48 years (SD 10). Liver toxicity was the attribute that emerged as the most important driver of patient preference (25.8%, relative importance out of 100%), followed by severe side effects (15.3%), delay to disability progression (10.7%), and common side effects (10.4%). The most important drivers of predicted non-adherence were frequency of daily dosing (17.4% out of 100%), hair thinning (14.8%), use during pregnancy (14.1%), severe side effects (13.8%), and diarrhea (13.0%). Conclusions Understanding the important concerns expressed by patients may help health care providers to understand and educate their patients more completely about these concerns. This knowledge may therefore improve both choices of appropriate therapy and adherence to therapy over time.

Burden of illness among patients with fragile X syndrome (FXS): a Medicaid perspective

Abstract Background: Fragile X syndrome (FXS) is an inherited intellectual disability that imposes a substantial clinical and humanistic burden on patients and caregivers. This study aimed to quantify the incremental burden of illness following FXS diagnosis in Medicaid populations. Methods: A retrospective matched-cohort study was conducted using FL, NJ, MO, IA, and KS Medicaid claims (1997–2012). Patients with FXS were matched 1:5 to a comparison group without FXS, based on age, gender, state, and continuous Medicaid coverage. Healthcare resource utilization and costs were compared among cohorts over 1 year following first diagnosis. Results: Overall, 697 patients with FXS were matched to 3485 non-FXS patients. Median age was 12.0 years; 82% were male. Newly diagnosed FXS patients were younger (median age: 7.0 years). During the follow-up, patients with FXS had significantly higher medication use, medical procedure use, medical specialist visits, and associated costs than the non-FXS comparison group. One-fourth of FXS patients filled prescriptions for stimulants, antipsychotics, or anticonvulsants; 25% of patients with FXS had speech and language therapy and 39% had physical therapy (versus 9%, 4% and 8%, respectively, for the comparison group). At least 44% of FXS patients visited a neurologist, cardiologist, otolaryngologist, or gastroenterologist; 92% of patients with FXS had an outpatient visit, 35% had an emergency room visit, and 34% used home services (compared to 31%–32%, 64%, 27%, and 10%, respectively, for the comparison group) (all p < 0.05). Patients with FXS had an incremental annual total healthcare cost of

Increasing patient participation in drug development

33,409 (2012

Determinants of high cost in multiple sclerosis patients: a claims and chart review study.

) per person relative to the comparison group, while newly diagnosed FXS patients had incremental total annual healthcare costs of

Relationship between brain volume loss and cognitive outcomes among patients with multiple sclerosis: a systematic literature review

17,617 (2012

Parent preferences regarding stimulant therapies for ADHD: a comparison across six European countries

) per person. Conclusions: Both established and newly diagnosed FXS were associated with significantly increased use of multiple medications and medical services, and increased healthcare costs. Treatments that could help reduce this disease burden are urgently needed.

Brain MRI lesions and atrophy are associated with employment status in patients with multiple sclerosis.

volume 33 NumBeR 2 FeBRuARY 2015 nature biotechnology I also concur that program graduates must be able to communicate effectively across a broad spectrum of audiences, from the highly scientific to the lay person. In fact, we offer specific courses, such as ‘Bioscience Communication’ and ‘Managing and Leading Biotechnology Professionals’, where students learn to work effectively with peers, supervisors and employees and write scientific abstracts, prepare scientific papers, as well as write for a general audience—these skills are critical. Our students must also have a background in the science of biotech, including biochemistry and cell biology, before entering the program. My original article discussed the virtual, recently created Society of International Bioentrepreneurship Education and Research (SIBER) in helping corral core competencies and leaders in bioentrepreneurship education. This is a growing field, and the effort at the University of Dublin is noteworthy. Since the article was published, I’ve heard from several other schools that had not been included. I invite you and others to attend the next meeting of SIBER this June in Copenhagen to further engage in the conversation. to fully transform discoveries into products for patients. Finally, we would like to point out that the box listing selected schools with bioentrepreneurship programs did not mention the Masters in Biotechnology and Business program that is organized at UCD between the M. Smurfit Graduate School of Business and the School of Biomolecular and Biomedical Science. Gauging the interest from international students, we consider this program worth bringing to the attention of your readers.

The real-world patient experience of fingolimod and dimethyl fumarate for multiple sclerosis

Abstract Objective: To identify factors associated with high cost multiple sclerosis (MS) patients using integrated administrative claims and medical charts data. Methods: This study identified newly diagnosed MS patients (≥18 years) in a large United States managed care claims database between 1 January 2007 and 30 April 2011 using the ICD-9-CM code (340.xx). Mean annualized MS-related costs higher than the third quartile were categorized as high cost, lower than the first quartile as low, and the rest as medium. Patients were compared across cohorts with descriptive and inferential statistics. Baseline high cost factors were identified with multivariable logistic regression models. Results: Administrative claims (n = 4342) and medical chart records (n = 400) data was evaluated. Mean (SD) annualized MS-related costs were