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AMI, utilizing its Specialty Pharmacy Database , has identified the specialty pharmacies focusing on rare diseases and provided profiles of each pharmacy.

AMI has published a related report in February on Specialty Pharmacy Centers of Excellence. Over 7, rare diseases affect more than 30 million people in the United States. Many rare conditions are life-threatening and most do not have treatments. Since the Orphan Drug Act was signed into law in , the FDA has approved hundreds of drugs for rare diseases, but most rare diseases do not have FDA-approved treatments.

The increase for orphan and rare diseases in the marketplace is resulting in a segment of specialty pharmacy that are focusing on rare diseases. Medicare Part B covers physician services, hospital outpatient care, certain home health services, certain clinical laboratory services, some preventive services, durable medical equipment, and certain drugs.

Covered drugs include drugs administered in physician offices that usually are not self-administered, drugs used as part of durable medical equipment e. Under these provisions, Part B covers certain orphan drugs that are administered by infusion or injection in a physician's office or clinic, for example, galsulfase Naglazyme , a treatment for Maroteaux-Lamy syndrome, a rare metabolic disorder.

Likewise, Part B typically covers certain orphan drugs that are administered at home using equipment that is covered by Part B. An example is dornase alfa Pulmozyme , a medication for cystic fibrosis that is inhaled using a neubulizer. In addition, Part B also covers drugs provided as part of hospital outpatient services.

These services are covered by a prospective payment system that includes inexpensive drugs and diagnostic radiopharmaceuticals as part of the packaged payment to an outpatient facility for a service such as a surgical procedure.

More expensive drugs and biologics are reimbursed separately MedPAC, The Medicare Prescription Drug Improvement and Modernization Act of changed the way that Medicare pays physicians for Part B drugs and drug administration services.

Policy makers agreed that the payment rates for Part B drugs were too high, but some providers argued that the high rates for the drugs were needed to offset payment rates for administering the drugs that were lower than the costs of administration.

Since , physicians who provide Part B drugs to their patients are reimbursed for those drugs at percent of the average sales price, which is computed as the average transaction price for all sales in the United States. The law provided that new biologics and single-source drugs brand-name drugs with no generic version would be paid based on an individually determined average sales price so that payment would not be coded or averaged with other products.

At the same time that Congress reduced reimbursement for Part B drugs, it increased the payment to physicians for administering the drugs. A report by the Medicare Payment Advisory Commission MedPAC concluded that the change to the new payment system resulted in lower Part B expenditures for almost all covered drugs, largely due to lower prices MedPAC, For example, from to , the drop in drug expenditures ranged from 1 percent for rheumatology Part B drugs to 52 percent for urology drugs.

Patients pay a general Part B deductible and then 20 percent of the Medicare-approved payment amount. A patient's Part B coinsurance liability for medications is not capped and stays at 20 percent no matter how expensive the drug.

However, as of , just over 90 percent of beneficiaries had some form of public or private supplemental insurance that shielded them from Part B cost sharing requirements MedPAC, b. Some drugs may be covered under Part B or Part D depending on the circumstances.

Several of these products were approved as orphan drugs for at least one, generally several, indications. Medicare Part D adds an outpatient prescription drug benefit to the Medicare program.

All Medicare beneficiaries have access to the benefit. Although they are not required to enroll, beneficiaries who do not enroll during their initial eligibility period and who do not have equivalent alternative coverage will pay more if they enroll later.

As of February , more than 26 million beneficiaries were enrolled in a Part D plan KFF, b. The Part D benefit is administered by private plans approved by CMS. Part D benefits are offered through stand-alone prescription drug plans and through Medicare Advantage plans that cover all Medicare benefits including medications.

Congress also specified that drug coverage for all individuals dually eligible for Medicare and Medicaid would shift from the Medicaid program to the Part D benefit. As a result, all dual eligibles are now enrolled in private Part D plans. com, Beneficiaries with low incomes and modest assets receive substantial financial assistance with Part D premiums and cost sharing.

For example, full-benefit dual eligibles pay no premiums, pay relatively nominal fixed copayments per prescription, and are not subject to the deductible or the coverage gap described below. Plans have the option to deviate from this standard benefit by offering an actuarially equivalent benefit or by offering enhanced benefits.

However, the vast majority of drug plans 80 percent offered no benefits in the coverage gap as of January , and most plans that did offer such benefits covered only generic drugs in the coverage gap KFF, b. Under the Affordable Care Act, beginning January 1, , Part D beneficiaries in the coverage gap will receive a 50 percent discount absorbed by the manufacturer off their plan's negotiated price for brand-name drugs and biologics covered by the plan.

Over the subsequent 10 years, the beneficiary's coinsurance for brand-name drugs in the coverage gap will drop annually or biannually, down to 25 percent by , and the coinsurance for generic drugs will likewise drop to 25 percent.

Within limits specified by the federal government, Part D plans have considerable flexibility in structuring formularies, imposing cost sharing requirements, and establishing procedures for managing drug utilization.

For companies making orphan drugs or considering development of an orphan drug, several features of Part D plans could significantly affect beneficiary access and costs. More details about these features as they affect orphan drugs are included in Appendix C.

Most Part D plans use tiered formularies. Generic drugs in tier 1 require the lowest copayment; brand-name drugs preferred by the plan in tier 2 require a somewhat higher copayment; nonpreferred brand-name drugs in tier 3 require a still higher copayment. Rather than paying a fixed copayment per prescription e.

Although the incentives in tiered formularies for beneficiaries to use generic or preferred drugs can provide leverage for plans to negotiate discounts with drug manufacturers, both the lack of competition for many orphan drugs and the small number of users for these drugs, as noted above, weaken the negotiating position of plans.

This assumes that the patient has no other applicable out-of-pocket costs. Depending on how the initiation of treatment matched the start of a coverage year, that period of more generous coverage could last as long as 6 months before the coverage cycle started anew.

A recent GAO b study reported that high-cost drugs i. It also reported that 55 percent of beneficiaries who used at least one specialty-tier drug exceeded the upper threshold of the coverage gap.

In addition, more than 75 percent of prescriptions for specialty tier-eligible drugs were for subsidized beneficiaries such as dual eligibles who qualify for reduced cost sharing for these and other drugs and who are not subject to the coverage gap.

In addition to patient cost sharing features, Part D plans also employ a variety of utilization management strategies to control the use of drugs and overall costs as well as to promote medication safety in some instances.

These include prior authorization, step therapy, and quantity limits. Other things being equal, a pharmaceutical company would expect less use of an orphan drug and lower profits if the drug were a target of the most stringent of these utilization controls.

Plans generally require enrollees to obtain prior authorization from the plan to secure coverage for certain medications, particularly higher-cost medications or drugs with particular safety concerns.

The committee found no data on the extent to which plans approve or deny requests for prior authorization. Plans also may employ what are termed step-therapy requirements for certain medications for which alternatives are available.

Under step therapy, enrollees are required to try a lower-cost medication and document a poor response to that drug before coverage of a higher-cost medication would be granted. Quantity limits i. In general, more frequent prescriptions to obtain the same quantity of a drug mean more costs shifted to patients.

FDA approval of a drug is for a specific indication or indications based on evidence of safety and effectiveness for each indication.

These indications are described in the FDA-approved labeling for the product. Physicians may legally prescribe drugs for off-label indications. For example, a drug approved for use with a common disease may be used off-label for a rare condition, and physicians likewise may prescribe an orphan drug for either a common indication or a rare indication other than the indication s for which it has been approved.

Some have expressed concern that some companies seeking orphan drug approval and marketing protection are really aiming at off-label use for a common indication and are inappropriately benefiting from the marketing protections attached to orphan drug approval Fugh-Berman and Melnick, ; Wellman-Labadie and Zhou, In addition to cost concerns, off-label use raises concerns about patient exposure to drugs that have not been determined to be safe and effective for uses other than those approved by FDA.

At the same time, such use may provide options for patients for whom FDA-approved products are limited or nonexistent because physicians can try a medically plausible treatment approach to a disease Kocs and Fendrick, ; Gillick, If case reports suggest promise from such an off-label use, then this may prompt companies or others to undertake controlled studies to support approval by FDA of a new indication.

Alternatively, because systematic research could contradict the promising case reports and thereby curtail off-label sales, companies may choose not to pursue further studies. Studies have indicated that off-label use is common in oncology see, e. Off-label use is likewise common in pediatrics.

Indeed, the lack of testing of drugs for use with children prompted legislation to encourage and in some cases require such testing see Chapter 3. One study of outpatient prescribing patterns reported that of more than medications covered in the study, 21 percent of uses were off-label and most of these off-label uses 73 percent lacked clinical evidence of efficacy Radley et al.

Even when off-label uses are backed by research, companies may not wish to incur the costs of pursuing FDA approval unless they expect such approval to encourage further use that will offset those costs.

The initial CMS regulations for the Part D program denied coverage of medications for off-label uses unless the prescribed use was supported by one of three specific medical compendia Le Masurier and Edgar, One concern is that questions have been raised about the independence of compendia compilers, the degree to which they cite current evidence or any evidence , the quality of their methods and their assessments of evidence, and the potential for official acceptance of such compendia to discourage research aimed at FDA approval of off-label uses Tillman and Gardner, ; Abernethy et al.

To inform future off-label coverage determinations, CMS commissioned a technology assessment from the Agency for Healthcare Research and Quality AHRQ to summarize the process by which anticancer drugs are added to various compendia and to identify methods used to collect evidence for listed drugs and biologics and their indicated uses Abernethy et al.

The assessment covered six compendia and a sample of 14 anticancer combinations that were selected to include newer and older agents, common and rare cancers, and biologics and drugs. Among the findings was that there was little agreement in the evidence regarding efficacy cited by the compendia and that the compendia were discordant on whether they discussed adverse effects among patients with specific cancers.

Moreover, when compendia did not include off-label indications, the analysts could not determine whether a particular omission reflected a conscious editorial decision following the evaluation of available evidence or whether the available evidence was not identified and evaluated.

The authors observed that although they could not generalize to other disease areas, the compendia's performance might be expected to be highest in oncology, given their importance for reimbursement.

The authors also pointed out the major challenges of managing a near-continuous systematic review of large numbers of drug uses not approved by FDA. They also noted that FDA itself was not authorized or prepared to undertake such a review.

For rare diseases, the volume of drugs and uses is obviously much smaller but so is the research to support evaluations of off-label use. The growing databases from Part D claims could, when linked to Medicare hospital and physician claims data, be a resource for studying the nature and outcomes of some off-label use of orphan and other drugs for patients with rare conditions.

Congress has not provided CMS itself with the authority to negotiate prices with pharmaceutical manufacturers. For many expensive drugs, including many orphan drugs, insurers may have little leverage in negotiating price discounts.

Given the introduction of Part D just 4 years ago, only limited empirical evidence has accumulated on its impact on drug prices.

A recent study by Duggan and Morton found that Part D led to a decrease in the average price for brand-name drugs and an increase in overall utilization of Part D drugs among Medicare recipients Duggan and Morton, They estimate that each percentage point increase in the pre-Part D Medicare market share for a given drug is associated with a 1.

However, Frank and Newhouse found some evidence that the shift from Medicaid to Part D of drug coverage for dual eligibles resulted in higher drug prices for this population. These analyses did not specifically consider orphan or specialty-tier drugs.

An analysis commissioned by MedPAC reported that prices for Part D drugs rose 11 percent between January and December based on national drug codes as the unit of analysis MedPAC, a. However, after taking into account the substitution of generic for brand-name drugs which is encouraged by Part D plans , the analysis found Part D prices declined by 3 percent over the same period.

Appendix C presents the results of a commissioned analysis of Part D plan coverage of orphan drugs as reported in the January CMS Prescription Drug Plan, Pharmacy Network, and Pricing Information Files.

For drugs that are not covered by Medicare Part B or, rarely, Part A and that thus are eligible for Part D coverage, the analysis found that the great majority are covered by more than half of Part D plans Table Of the handful of orphan drugs that were not covered by any plan as of January , several of these have now been added to the formularies of at least one plan.

In addition, several drugs that were included in the analysis because they were not in the CMS price list for Part B-covered drugs have since been added to that price list. Coverage of Part D-Eligible Drugs by Type of Medicare Prescription Drug Plan. There are some differences in coverage of orphan drugs across different types of Part D plans.

For example, overall, orphan drug coverage seems to be somewhat more generous among national stand-alone Part D plans than among nonnational stand-alone plans. For orphan drugs, 27 percent are covered by fewer than half of nonnational plans, while only 9 percent are covered by fewer than half of national plans.

Still, Medicare beneficiaries who rely on an orphan drug should be able to find a Part D plan that covers it. Although nearly all orphan drugs are covered by at least half of Part D plans, significant limits of the kinds described above typically apply. Almost half 46 percent of orphan drugs are included in specialty tiers by 50 percent or more of stand-alone Part D plans.

One-third of orphan drugs were subject to prior authorization requirements before coverage is granted by 50 percent or more of stand-alone plans. The Medicaid program, which is jointly financed and administered by the federal and state governments, covers health and long-term care services for approximately 20 percent of Americans under age 65, including eligible low-income children, parents, and individuals with disabilities EPI, It also covers eligible low-income individuals over 65 who are covered by Medicare.

Under the Affordable Care Act, state Medicaid programs will be required to extend eligibility to all individuals with income up to percent of the federal poverty level. One estimate is that this eligibility expansion could increase Medicaid enrollment by approximately 16 million individuals Holahan and Headen, Although states are not required to cover prescription drugs in their Medicaid programs, all 50 states and the District of Columbia offer a drug benefit KFF, As noted above, prescription drug coverage for individuals who are dually eligible for Medicare and Medicaid shifted from Medicaid to the Medicare Part D program as of January Other Medicaid beneficiaries still receive drug coverage from their state Medicaid program.

Under the Medicaid Rebate Program, manufacturers are required to have a rebate agreement with the Secretary of Health and Human Services in order for states to receive federal Medicaid funding for outpatient prescription drugs dispensed to Medicaid patients.

Until , the rebate had been Under the Affordable Care Act, the minimum rebate for innovator drugs will increase in to The rebate for noninnovator drugs will increase from 11 to 13 percent of AMP.

Under the new law, Medicaid rebates must be paid on outpatient drugs dispensed to enrollees of Medicaid managed care plans close to 70 percent of all Medicaid enrollment , which was not the case before Overall, the rebate provisions make orphan drugs more affordable for state Medicaid programs, although very expensive drugs remain very expensive.

The committee found no analysis specific to orphan drugs, but some evidence suggests that this rebate approach results in much lower prices for Medicaid than for other payers in the market. For example, the House Committee on Oversight and Government Reform estimated that Medicaid pays prices that are about 30 percent lower than prices paid by Medicare Part D Outterson and Kesselheim, However, a study by Duggan and Morton found that drugs sold disproportionately to Medicaid beneficiaries have higher prices than otherwise similar drugs.

Because the Medicaid rebate is based on prices paid for these drugs in the private sector, manufacturers have an incentive to increase prices charged in the private sector, thereby distorting both the private market price and the Medicaid price.

In response to increasing prescription drug utilization and expenditures, states have adopted a variety of cost containment approaches over the past decade.

For example, according to an analysis of the 50 states and the District of Columbia, 44 states have state maximum allowable cost programs that set maximum reimbursement levels for generic and multisource brand-name drugs, and 26 states were members of multistate purchasing coalitions intended to increase negotiating power over price with pharmaceutical manufacturers Smith et al.

Forty-four states negotiate supplemental rebates in addition to rebates negotiated through the national drug rebate program for Medicaid. Almost one-third 16 states limit the number of prescriptions that are covered per enrollee, and 46 require prior authorization before granting coverage of specific medications as of There are also online butchers specializing in rare cuts of meat, seafood delivery services with sushi-grade fish and online cheese shops rife with Roquefort and Brie.

If you'd rather someone do the curating for you, I'll point you to our list of the best snack subscription boxes from around the globe.

But to kick your next dinner party into high gear or nab some truly special snacking supplies, we've rounded up the best specialty online food markets for every type of home chef. While some online shops might be best for one specific category -- fish, meat, spices -- iGourmet has the best selection across all categories.

At this sprawling online market, you'll find a spread of savory and items including gourmet cheese, fancy pantry staples, imported sauces, oils, crackers, fresh meat and seafood. iGourmet carries tons of specialty producers from every corner of the globe, although there's a bit of a French influence you can feel as you scroll the expansive site.

After the many pages of cheese to peruse, my favorite section to scroll through has got to be the savory snacks. There you'll find munchable treasures like cranberry hazelnut crackers , hot pepper vinegar chip s and lemon-ginger butter biscuits.

The high-end online grocery has meal kits and bundles along with subscriptions for monthly shipments of goods including cheese, charcuterie and bacon. is an online market specializing in Asian and Mexican foods. Here you'll find an eye-popping inventory of fresh produce, pantry items, spices, sauces, frozen foods, noodles galore, snacks, drinks, cosmetics and more.

Food items are broken down by category but you can also search by the country of origin including foods from China, Taiwan, Japan, South Korea, India, the Philippines and Mexico.

Need chili crisp? You'll find several varieties of addicting sweet and spicy condiments and plenty of other sauces to give your next stir-fry a punch. has those too. only offers fresh food delivery in the San Francisco Bay Area and Seattle, currently. But it ships dry goods, pantry items and snacks by mail to other regions of the US.

To find out if Weee! ships to your region, punch in your ZIP code. Umamicart is another popular new online market specializing in Asian groceries.

If you can't find what you're looking for at Weee! I could spend hours scrolling the frozen dim sum alone but just about every food category is bursting with options you won't likely find in your local market.

Craving a bag of those salty shrimp chips you discovered abroad but can't find here? When you can't stroll down a busy Tuscan market, Supermarket Italy is the next best thing for scoring Italian goods for your next festa.

Supermarket Italy is a trusted importer of Italian and European goods -- both luxury and budget-friendly -- sourcing items from the highest quality vendors in Europe.

Get just about any type of pasta, sauce, cheese, spices and coffee along with cured meats and jars of olives and artichokes for the most decadent antipasti plate outside of Rome.

If it's cans of San Marzano tomatoes and artisan pasta you're after, Ditalia is a good place to find it all. This importer of specialties has all you'll need for Italian night including pantry staples, premade sauces, salumi, cheese and pasta. Ditalia isn't a budget retailer by any stretch.

The online Italian market carries groceries from some high-end producers based in Italy and elsewhere. With a massive supply of risotto rice, white beans, polenta and penne, it shouldn't be hard to do. There are dozens of excellent options for ordering seafood online.

I've tested a whole bunch of them which you can read more about here. For the best selection of high-quality fish, shellfish and other fresh seafood, Fulton Fish Market is my favorite. Fulton also carries heaps of clams, oysters , caviar and fish roe along with sauces and seasonings to make your fish sing on the grill.

I found Fulton's prices to be competitive when compared to other vendors in the category. Most of the fish is flash-frozen at peak freshness and shipped right away.

That means it's probably fresher than what you find at the supermarket since that seafood is often frozen, thawed and then laid out on ice for purchase. This online arm of New York's sprawling seafood market has hundreds of varieties of fish to choose from including filets you most likely won't find in your local shops like fresh barramundi and whole dover sole.

Much like seafood delivery options, there are a host of excellent specialty online butchers. If you're looking for wild boar, venison, duck breast or quail, this online meat shop is your best bet for finding it.

Rastelli's and Porter Road are two of my favorite online butchers, generally, but for specialty meats D'Artagnan has the best selection of unique cuts, wild game and charcuterie.

D'Artagnan has staples in spades -- chicken , ground beef , pork chops and bacon -- but the online butcher also carries a range of rare cuts, charcuterie and pantry goods to fancy up your next barbecue.

iGourmet sports a dizzying display of cheese. The online market stocks favorites including aged cheddars and creamy bries but also less common creations such as Baldauf Chilikase and French raclette. iGourmet has just about any type of cheese you can dream up and the site makes it easy to find them, too.

You can search by country, region, cheese type or producer. The cheese is mostly all cut and packaged directly by iGourmet it'll let you know when it's not which means prices are as fair as any I've seen from a high-end online cheesemonger.

If you seek spice in your life, Spicewalla has a staggering supply of individual spices and spice mixes to stock your rack.

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