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MS drug clinical trial success rate was 27% compared to a 10% industry rate.
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Clinical trial success rates in MS surpass that of industry across all phases.
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Small molecule drugs have a higher overall success rate compared to biologics in MS.
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Phase II trials enrolling “Relapsing MS” populations best predict Phase III success.
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MS-tested drugs with prior FDA approved had lower success rates than novel drugs.
Abstract
Objective
To determine the risk of clinical trial failure for new drugs in multiple sclerosis (MS) and to identify factors that could improve outcomes.
Methods
We collected data on compounds that were tested in MS from Phase I to Phase III clinical trials between 1998 and January 2015. Clinical trials success rates were calculated and compared to industry standards. The exclusion criteria for the drugs in this study were: drugs that commenced Phase I in MS prior to 1998, non-industry conducted trials, trials testing non-disease modifying drug treatment, and trials testing combinations of drugs already approved by the FDA.
Results
Fifty-three distinct drugs met our inclusion criteria. The cumulative success rate for MS drugs was 27%, almost triple the 10% industry rate. Clinical trial success rates in MS surpass that of industry across all phases. Phase II clinical trials completed in a "Relapsing MS" population were most successful in predicting Phase III clinical trial success. Small molecules were found to have a higher overall success rate compared to biologics; however, both drug technologies largely pursue different molecular targets. Drugs that were previously FDA approved for another indication and were subsequently tested in MS had lower success rates than drugs that had no previous FDA approval history.
Conclusions
Overall, MS enjoys almost triple the clinical trial success rates of other disease areas. In addition, small molecules are superior to biologics in MS and novel drugs are superior to drugs with a previous FDA approval history outside MS.
The rapid expansion in the armamentarium of multiple sclerosis (MS) therapeutics is widely considered an exemplary achievement of modern drug development. In the span of approximately 20 years, therapeutic options for patients with MS increased from solely steroids to eleven FDA approved disease-modifying therapies (DMT's), ranging from injectable biologics to the more recently approved small molecule drugs (
). It is considered even more remarkable that the majority of the drug approvals occurred during a time when the FDA approved 25% fewer drugs on average than in past decades, despite increases in research and development spending (
). Although the sudden progress in DMT's for MS is encouraging, the therapeutic landscape for MS is far from complete as there is a particular dearth of therapeutics indicated for progressive MS. Additionally, although studies have quantified clinical trial risk in the drug industry as a whole, (
) to our knowledge, no study has quantified the clinical trial success and attrition within this particularly “successful” disease area. Therefore, the aim of our study was to quantify clinical trial risk in MS as it compares to failure rates in the drug industry as a whole and to highlight clinical trial risk factors specific to MS with the view to improve future decision making in MS drug development. The study applies methodology reported previously in several publications examining clinical trial attrition in disease areas such as prostate cancer, lung cancer, Crohn's disease and rheumatoid arthritis (
), Phase I, II and III clinical trials evaluating investigational drugs for the treatment of multiple sclerosis in its varying subtypes—relapsing-remitting (RRMS), secondary-progressive (SPMS) and primary-progressive (PPMS)—were analyzed. Clinical trials for drugs that were intended to treat secondary complications of MS, such as spasticity, fatigue and cognitive impairment, were excluded from the study. Only drugs being developed as “disease-modifying therapy” were included. Additionally, the trials must have been industry sponsored and Phase I trials must have been completed after 1998. Drugs being tested in combination with other drugs were included so long as one of the drugs being tested was not already FDA approved for the purposes of MS.
2.2 Database and online tools
The primary information source used for this study was the public, online, clinical trial database: http://clinicaltrials.gov/. “Multiple sclerosis” was used as the primary search term and the results were filtered based on the above stated inclusion criteria. Additional research outside the scope of this database was completed using publically available Internet resources, press releases, and online journals/periodicals (accessed through University of Toronto Libraries).
2.3 Classification of cinical trial success
A simple, transparent, and previously established rule was applied to classify clinical trial outcomes (
). In order to be considered a Phase I clinical trial success, a compound must have completed a Phase I clinical trial and subsequently transitioned to a Phase II clinical trial. Similarly, a compound was classified as a Phase II clinical trial success if it subsequently moved on to Phase III, and a Phase III clinical trial success if the compound was granted Food and Drug Administration (FDA) approval for MS. Compounds in Phase I/II clinical trials were considered to be in Phase I, and compounds in Phase II/III clinical trials were considered to be in Phase II. Therefore, a compound that completed a Phase I/II clinical trial and moved on to Phase II/III clinical trials was considered a Phase I success. Additionally, compounds transitioning from Phase IIa to Phase IIb were not considered Phase II successes. Similarly, a transition from Phase II to Phase II/III was considered a transition from Phase IIa to Phase IIb, and therefore not considered a Phase II success.
Compounds with registered Phase II and/or Phase III clinical trials but missing Phase I clinical trials registered on clinicaltrials.gov were “backfilled” as Phase I clinical trial successes as long as the Phase II trial began no earlier than the year 2000. Similarly, compounds undergoing Phase III clinical trials with absent Phase II clinical trials were backfilled as Phase II clinical trial successes. This was typically the case if the compound with the missing Phase II was analogous to a previously tested drug (with Phase II data), or the drug was being tested in a new disease subtype after already undergoing a Phase II trial in another MS subtype.
In exceptional cases, a drug was considered a Phase II success if it moved on to Phase III based on the interim date of an ongoing Phase II trial. After applying these criteria, the clinical trial transition probability was calculated by determining the percentage of unique drugs that successfully completed a phase of development out of the total number of drugs tested in a particular phase of development, as demonstrated using the following equation:
Transition probability for Phase x=(# of drugs passed to Phase x+1) ((# of drugs that passed to Phase x+1)+(# drugs that failed at Phase x))
Data was collected from clinicaltrials.gov up until 1 January 2015, at which point the dataset was officially closed.
2.4 Classification of clinical trial failure
Clinical trial failures were categorized as either clinical or commercial. A compound was deemed a clinical failure if it failed to progress to the next phase of clinical testing because the most advanced trial raised safety concerns and/or failed to meet it's primary endpoint. Conversely, a compound was considered a commercial failure if it failed to progress to a subsequent clinical trial within two years of the most recent trial completion date, despite press reports or publication of positive clinical trial results.
Occasionally, pharmaceutical companies chose to discontinue clinical trials for an efficacious compound in order to develop a newer, analogous agent to be tested in its place. In this event, the first compound was considered a commercial failure, despite its proven efficacy, and the analogous agent was treated as a separate entity undergoing it's own stream of clinical trials. Additionally, because this study includes only industry-sponsored trials, drugs were considered failures if industry sponsored trials were abandoned whether or not a public institution chose to conduct further testing.
2.5 Compound classification
Compounds were classified as either small molecules or biologics. Biologics were determined in accordance with the FDA definition, which includes “vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins” (
). Any active compound that did not fall within this definition was considered a small molecule. Compounds were categorized as previously FDA approved drugs if they received approval for another indication prior to undergoing MS clinical trial testing. In order to be included in this category, the drug being tested for MS must have been in the exact form as the drug that was FDA approved; metabolites of FDA approved drugs or similar compounds were categorized as drugs with “No prior FDA approval history”.
2.6 Classification of clinical trial study population
Clinical trial study populations were determined for Phase II and Phase III clinical trials using the trial inclusion and exclusion criteria listed on clinicaltrials.gov. Considering Phase I studies were completed in a wide variety of study populations, including healthy volunteers, we chose not to classify Phase I study populations. Phase II and Phase III clinical trials enrolled one of the following study populations: relapsing remitting MS (RRMS), secondary progressive MS (SPMS), “Relapsing MS” (RRMS or SPMS with relapses), or primary progressive MS (PPMS). A given compound may have undergone more than one Phase II or III clinical trial, each in a separate study population; in this event, the drug was treated as a separate entity for each of the subtypes it was investigated in. For example, a single drug may undergo a distinct series of clinical trials enrolling patients with one MS subtypes (i.e. RRMS) and another enrolling patients with a different MS subtype (i.e. PPMS). In this event, the compound may be successful in one of the subtypes (i.e. RRMS) while failing in the other (i.e. PPMS), and would therefore be reflected in the dataset twice. Occasionally, approved MS drugs were tested in a progressive population following their FDA approval for use in a RRMS/RMS population. In this case, the start date of the drug's original Phase I clinical trial, which was likely prior to 1998, was not an exclusion factor, given that the established safety profile eliminates the need for a new Phase I trial to be completed prior to investigating the progressive subtype.
3. Results
The search term “multiple sclerosis” in clinicaltrials.gov returned 1247 trial results. Amongst these trials, 53 distinct compounds met our outlined inclusions criteria. Furthermore, five of these distinct compounds underwent two streams of clinical trial testing within different MS subtypes. Consequently, these five drugs are reflected in the dataset twice, once per disease subtype being investigated, lending a total of 58 clinical trial histories for analysis. Of these 58 series of clinical trials, 28 failed to progress at a given phase while 25 clinical trials remained in progress. Additionally, five compounds received FDA approval for MS during the study time frame—Tecfidera, Aubagio, Gilenya, Lemtrada and Plegridy —all of which are approved for “relapsing forms” of MS (
Fig. 1 displays the cumulative clinical trial success rate of drugs in MS as compared to reported industry-wide success rates for all disease indications (
). From these data, MS clinical trial success rates exceed industry expectations across all phases, with a cumulative pass rate of 27% compared to the 10% industry rate.
Fig. 1Clinical trial success rates for MS are shown alongside drug industry-wide clinical trial success rates (
). Transition probability is a measure of a compounds probability of successfully transitioning from Phase I to Phase II, Phase II to Phase III, or Phase III to FDA approval. The sample number above each column is the sum of the number of drugs that failed and the number of drugs that passed the corresponding phase, and therefore excludes the number of drugs that are currently conducting that phase. The cumulative pass rate is an expression of the product of the transition probabilities in each of the three clinical trial phases.
Although Fig. 1 provides a broad overview of clinical trial success in MS as a whole, Fig. 2 provides a more detailed analysis of the performance of each MS subtype in Phase II and Phase III. Most significantly, Phase II clinical trials completed in a “Relapsing MS” population were most successful in predicting Phase III clinical trial success, as seen by the 100% Phase III success rate for drugs tested in patients with “Relapsing MS” (Fig. 2). Furthermore, the cumulative success rate of “Relapsing MS” trials was 39% (Fig. 2) compared to the 22% cumulative RRMS success rate and the 27% cumulative success rate of all MS subtypes combined (Fig. 1).
Fig. 2Phase II and Phase III clinical trial success rates of drugs as a function of the study population they were conducted in. The “Relapsing MS” category includes trials that enrolled patients who experienced relapses regardless of whether they had RRMS or SPMS. The cumulative pass rate is the product of the “Varied MS Subtype” transition probability and the corresponding Phase II and Phase III subtype transition probabilities. Backfilled Phase II successes: 2 for RRMS, 2 for SPMS, 2 for PPMS and 1 for “Relapsing MS”.
Despite the superiority of a “Relapsing MS” population, the majority of clinical trials were completed in an exclusively RRMS population (n=22), while only four clinical trials (three Phase II trials, of which two were backfilled, and one Phase III trial) were completed in a PPMS population. To date, no Phase III clinical trials enrolling exclusively PPMS or SPMS patients have been successful; however, there is currently one ongoing Phase III clinical trial for PPMS (ocrelizumab) and three for SPMS (BAF312, Tysabri and RPC1063). Thus, it is difficult to interpret the success of Phase II SPMS and PPMS trials in predicting Phase III success until these Phase III trials are complete.
Out of the 53 compounds included in the dataset, there were slightly more biologics than small molecules (28 versus 24, respectively). The drug RNS60, a charge-stabilized nanostructure without any “active” medical ingredient, was considered neither a small molecule nor a biologic and was therefore excluded from this section of the analysis (
). Fig. 3 compares the transition probability of MS small molecules and biologics in relapsing and non-relapsing MS disease populations, alongside industry-wide values (
). Transition probabilities for MS biologics are lower than that for MS small molecules across all phases, regardless of the MS subtype being investigated (Fig. 3). The cumulative success rate of MS biologics is less than that of the industry biologic success rate (23% versus 32%) while the cumulative success rate of MS small molecules is greater than that of industry small molecules (31% versus 13%). However, it is important to note that the 100% Phase II transition probability for SPMS/PPMS small molecules was comprised of three drugs with backfilled Phase II's.
Fig. 3Clinical trial success rates for biologic and small molecule drugs in relapsing-MS (RRMS/RMS) and progressive-MS (SPMS/PPMS) are displayed alongside biologic and small molecule industry wide clinical trial success rates (
). One drug from the dataset was excluded from this analysis as it was neither a small molecule or biologic by definition. Backfilled Phase II successes: 3 for RRMS/RMS biologic, 0 for RRMS/RMS small molecule, 1 for SPMS/PPMS biologic, 3 for SPMS/PPMS small molecule. The “combined” transition probability is the product of the RRMS/RMS and SPMS/PPMS transition probabilities of the same drug class for the same phase.
Interestingly, the one category in which small molecules were not superior to biologics was in SPMS/PPMS Phase III's, wherein one of each drug class were tested and failed. Table 1 lists the molecular targets of small molecules and biologics and reveals C–C chemokine receptor type 2 (CCR2) as the only target shared by both drug types. Therefore, within MS, small molecules and biologic drugs interact predominantly with different targets.
Table 1List of the small molecule and biologic drugs included in the analysis and their corresponding molecular targets.
The MS clinical trial success of compounds with a previous history of FDA approval in another disease indication outside MS was compared across MS subtypes to that of compounds without any prior FDA approval history. Compounds with prior FDA approval had a lower cumulative success rate than drugs without FDA approval history in all phases other than Phase I (Fig. 4). Lemtrada is the only FDA approved drug for MS that was originally approved in another disease area. Table 2 outlines the MS clinical trial history for the 11 drugs with previous FDA approval in another indication, along with the type of failure classification. As Table 2 reveals, slightly more of the previously FDA approved drugs failed clinically (n=4) than commercially (n=3).
Fig. 4Clinical trial success rates for drugs that were being tested in different MS subtypes but already FDA approved in another indication compared to clinical trial success rates of drugs that had no prior FDA approval history. Backfilled Phase II successes: 1 for RRMS/RMS orange, 2 for RRMS/RMS blue, 0 for SPMS/PPMS orange, 3 for SPMS/PPMS blue. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Abatacept is currently conducting a phase II trial in MS sponsored by the National Institute of Allergy and Infectious Disease (NIAID) however, the drug is considered a fail for the purpose of our analysis because this trial is not industry sponsored.
Clinical
Minocycline+Rebif
Antibiotic+Approved MS
Phase 1 outside MS
Failed
Clinical
Minocycline+Copaxone
Antibiotic+Approved MS
Phase 1 outside MS
Failed
Commercial
Daclizumab
Organ Rejection (1997)
Phase 1 outside MS
Passed
Current
Alemtuzumab
Chronic Lymphocytic Leukemia (2001)
Passed (MS)
Passed
Passed
Cladribine
Hairy Cell Leukemia (2004)
Phase 1 outside MS
Passed
Failed
Clinical
a Abatacept is currently conducting a phase II trial in MS sponsored by the National Institute of Allergy and Infectious Disease (NIAID) however, the drug is considered a fail for the purpose of our analysis because this trial is not industry sponsored.
Additionally, Fig. 5 distinguishes between commercial and clinical failures for all drugs in the dataset that failed any phase. Interestingly, commercial failures were more common overall in MS than clinical failures in Phase I and Phase II. Not surprisingly, Phase III failures were exclusively clinical failures.
Fig. 5The number of commercial and clinical failures out of the total number of failures across all three phases for each MS subtype.
), none have investigated clinical trial risk within MS. The aim of this study was to quantify the risk of clinical trial attrition in MS drug development in comparison to industry trends, and identify MS-specific clinical trial failure trends to elucidate areas of underperformance. Our findings suggest that MS clinical trials outperform results seen in other disease indications. In addition, we examined the outperformance of small molecules in comparison to biologics in MS. Our findings suggest small molecules are superior to biologics in MS, yet small molecules and biologics pursue different sets of molecular targets. Finally, we compared the MS clinical trial success of drugs with prior FDA approval in a disease area other than MS with that of drugs without prior approval to determine if prior approval reduced MS clinical trial failure risk. Our study found that testing drugs with previous FDA approval carried greater failure risk than testing new drugs specifically developed for MS.
The clinical trial success rate for drugs in MS was found to be 27%, based on 58 clinical trial histories of 53 drugs that met our inclusion criteria, which is nearly three times the 10% industry-wide success rate (
). Of the 8 drugs that underwent Phase III trials in our dataset, three were failures. We searched for trends that may suggest probable cause for the underperformance of these three Phase III trials. Of these three failures, two trials were completed in patient populations with progressive forms of MS (Dirucotide in SPMS and Gilenya in PPMS). Additionally, the Phase III failure of Dirucotide may be attributed to its premature progression from Phase II to Phase III, as it progressed to Phase III while still undergoing a Phase II/III trial. This Phase II/III trial was ultimately unsuccessful, leading to the termination of the ongoing Phase III trial (
). Additionally, Gilenya progressed prematurely to a PPMS Phase III trial as well, as it did not complete a Phase II trial in a progressive population, likely because it had already gained approval for relapsing forms of MS.
Cladribine was the third drug to fail Phase III, however this trial was completed with RRMS patients. Yet, similar to Dirucotide and Gilenya, Cladribine did not have a Phase II trial registered on clinicaltrials.gov with a start date prior to the earliest registered Phase III trial. A literature search revealed that this drug was tested in multiple clinical trials during the early to mid-1990s (
). During this timeframe, Cladribine was tested in progressive MS populations, however its progress came to a halt following inconclusive Phase III results (
). Cladribine's clinical trial history in progressive MS is not reflected in our dataset because the trials were completed prior to 1998; however, Cladribine completed a successful Phase II RRMS trial, for which results were published in 1999 (
). This late 1990s trial is the latest Phase II trial preceding the most recent failed Phase III trial. Although this Phase III trial demonstrated efficacy in RRMS patients (
). Therefore, perhaps the risk of Phase III failure may have been mitigated if a more recent and updated Phase II trial was completed. Overall, these observations suggest the potential importance of completing a successful and recent Phase II prior to the commencement of a Phase III trial to help mitigate Phase III failure risk.
Additionally, during our timeframe small molecule drugs largely dominate clinical trial success in MS compared to biologics. This discrepancy in success was largest in Phase III trials completed in RRMS/RMS populations. This is in contrast to reports in the literature that have found greater clinical trial success rates for biologics compared to small molecules (
). Conversely, this finding is congruent with results of clinical trial success rates in breast cancer, which show increased success of small molecule in clinical testing beyond Phase I (
). As a whole, these results suggest that whether or not biologics or small molecules are superior is dependent on the disease area. Moreover, perhaps the traditional domination of biologics versus small molecules may be attributed to the confounding variable of differing molecular targets. A comparison of the known drug targets of the small molecules and biologic drugs in our sample (Table 1) revealed there was little overlap between the targets of small molecules and biologics, whereas there was substantial target overlap within each drug type.
In MS, at least, the superiority of small molecules to biologics may reflect the drug technology itself or the target choice. Considering the case that small molecule MS drug success is a reflection of the superiority of the small molecule targets rather than the superiority of small molecule drug technology, perhaps testing biologics aimed at small molecule targets may further enhance success given the suggested superiority of the biologic technology (
). Conversely, perhaps the success of small molecules in treating MS is due to their ability to cross the blood-brain barrier (BBB) and interact with cells of the central nervous system (CNS). Fingolimod, the first approved oral MS drug, has been shown to cross the BBB where it may have direct effects on CNS cells (
). If this is the case, biologics may be inferior to small molecules in MS because of their inability to effectively traverse the BBB. Technology developed to increase the brain penetration and potency of monoclonal antibodies may therefore prove useful in MS (
The higher success rate of novel drugs developed for MS compared to previously FDA approved drugs is of interest as well. A theoretical advantage of undergoing clinical trials in MS with previously FDA approve drugs is that the safety of that drug has already been largely explored, offering the potential advantage of reduced clinical trial attrition due to safety concerns. However, four out of the seven failures of previously approved drugs were determined to be clinical, rather than commercial, failures. Rituximab is an interesting example of a commercial failure in which the drug showed impressive Phase II efficacy (
); however, instead of pursuing this drug further, Roche chose to develop an analogous, but humanized, monoclonal antibody called ocrelizumab, which although similar to rituximab, was expected to show improved benefit with reduced risk. However, a Phase II study of ocrelizumab revealed increased serious adverse events compared to rituximab (
), yet the compound continued to pursue Phase III testing in RRMS and PPMS. Interestingly, positive efficacy and safety for both RRMS and PPMS Phase III studies were recently announced at the 31st congress of the European Committee for Treatment and Research in Multiple Sclerosis (
Roche, 2015. Roche's ocrelizumab first investigational medicine to show efficacy in people with primary progressive multiple sclerosis in large Phase III study. In: Investor update [online]. Available at: 〈http://www.roche.com/investors/updates/inv-update-2015-09-28.htm〉, (accessed 10.31.15).
). Despite these results, FDA approval of ocrelizumab in RRMS and/or PPMS is required before it can be classified as a Phase III success in our dataset.
Finally, the results of this study overwhelmingly reveal the sheer dearth and failure of clinical trials enrolling patients with progressive forms of MS. Some have suggested the main reason for failed drug development in progressive MS is due to a lack of understanding of the pathophysiology of progression (
). There is currently no FDA approved drug for the treatment of PPMS; however, there are drugs in Phase II and III testing for PPMS treatment. Ocrelizumab recently released the first positive Phase III trial results in a PPMS population and will be seeking FDA approval in early 2016 (
Roche, 2015. Roche's ocrelizumab first investigational medicine to show efficacy in people with primary progressive multiple sclerosis in large Phase III study. In: Investor update [online]. Available at: 〈http://www.roche.com/investors/updates/inv-update-2015-09-28.htm〉, (accessed 10.31.15).
). Furthermore, Gilenya is undergoing a Phase III extension trial as a follow-up to its recently failed Phase III PPMS trial. Results remain pending at the time of this writing on the MIS416 Phase II/III clinical trial in PPMS. Additionally, masitinib, laquinomod, and ibudilast are all in the process of Phase II PPMS or PPMS/SPMS trials. In regards to compounds for the treatment of relapsing forms of MS, the results of this study seem to suggest higher clinical trial success when testing the compound in patients with “Relapsing forms” of MS rather than RRMS exclusively.
In conclusion, with a cumulative pass rate of 27%, the risk of failure in drug development for MS is much lower than industry expectation. The results of this study suggest small molecules are superior to biologics in MS for reasons that are yet to be fully determined, but could be the result of differences in target selection. Prior FDA approval of drugs in an alternate indication does not confer a reduction in clinical trial risk for MS, and clinical trials in “Relapsing MS” populations are more successful than any other disease subtype.
The methodology applied to examine clinical trial outcomes has limitations that have been discussed previously (
). Most importantly, the sample sizes are small and this should be regarded as a descriptive study, where the robustness of the findings will need to be tested by revisiting MS over time. Furthermore, the sample sizes for clinical trials completed in PPMS/SPMS populations are much smaller than those in RRMS/RMS and therefore limit our ability to draw bold conclusions and comparisons between the clinical trial performances of MS subtypes. Additionally, our primary information source (clinicaltrials.gov) is a US based third-party source that may not be indicative of the larger MS clinical trial landscape.
Finally, four drugs in the dataset were considered commercial failures because clinical trial results were not published and the drug did not undergo further development. However, there is always the possibility that the development of these drugs was terminated for clinical reasons not disclosed by the firm. It is also important to acknowledge that the results of this study are dependent on the assessed time interval, which as a result of the nature of our inclusion/exclusion criteria excluded numerous clinical trials that lead to the approval of first-generation MS biologics. Over time, the results of this study may be challenged by the approval of emerging next-generation biologics; however, this study depicts the most current MS drug development trends.
Disclosures
C. De Gasperis-Brigante reports no disclosures.
J. Parker worked in the pharmaceutical industry and advises a hedge fund that may or may not have investments pertaining to any products mentioned in this study.
P.W. O’Connor receives consulting fees and/or research support from Actelion, Bayer, Biogen Idec, BioMS, Cognosci, Daiichi Sankyo, EMD Serono, Genentech, Genmab, Novartis, Rocher, Sanofi-Aventis, Teva, Warburg Pincus.
T.R. Bruno received honoraria from Biogen, Teva, EMD Serono, Novartis, Allergan, Medtronic (some via MS Society unrestricted educational grants). She is a member of the advisory board for the use of Dalfampridine in MS and Equitable Access to Rehab Advisory Board. She also participated in the Allergan Academy of Excellence and has been an expert reviewer for the MS National Exercise Guidelines and Toolkit generation.
Funding
This study was funded by the Reasearch Opportunity Program at the the University of Toronto Mississauga. The sponsor of the study was not involved in the design and execution of the study.
Acknowledgments
This study was funded by the Reasearch Opportunity Program (ROP) at the the University of Toronto Mississauga.
Roche, 2015. Roche's ocrelizumab first investigational medicine to show efficacy in people with primary progressive multiple sclerosis in large Phase III study. In: Investor update [online]. Available at: 〈http://www.roche.com/investors/updates/inv-update-2015-09-28.htm〉, (accessed 10.31.15).
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