In December 2009, the Saban Center for Middle East Policy conducted a day-long simulation of the diplomatic and military fallout that could result from an Israeli military strike against the Iranian nuclear program. In this Middle East Memo, Kenneth M. Pollack analyzes the critical decisions each side made during the wargame.

The simulation was conducted as a three-move game with three separate country teams. One team represented a hypothetical American National Security Council, a second team represented a hypothetical Israeli cabinet, and a third team represented a hypothetical Iranian Supreme National Security Council. The U.S. team consisted of approximately ten members, all of whom had served in senior positions in the U.S. government and U.S. military. The Israel team consisted of a half-dozen American experts on Israel with close ties to Israeli decision-makers, and who, in some cases, had spent considerable time in Israel. Some members of the Israel team had also served in the U.S. government. The Iran team consisted of a half-dozen American experts on Iran, some of whom had lived and/or traveled extensively in Iran, are of Iranian extraction, and/or had served in the U.S. government with responsibility for Iran.

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Introduction

The issue of Iran has become a central preoccupation for the international community in recent months, thanks to the intersection of the historic changes in the region, an American presidential election, sharpening rhetoric from Israel, and Tehran’s relentless determination to advance its nuclear capabilities. The focus of policymakers in Washington and around the world remains fixed on the options for forestalling Iran’s determined march toward a nuclear weapons capability. This is the appropriate objective; the best possible outcome for maintaining peace and security in the Gulf and avoiding a deeply destabilizing nuclear arms race remains a credible, durable solution that curtails Iran’s nuclear ambitions. And while achieving such an outcome remains profoundly problematic, largely as a result of Tehran’s intransigence, preventing Iran from crossing the nuclear weapons threshold—either through persuasion, coercion, or some combination of the two—remains fully and unambiguously within the capabilities of the international community.

The shadow cast by Tehran has created a particularly intense sense of existential anxiety for the smaller Gulf states, including Kuwait, Bahrain, the United Arab Emirates, Qatar, and Oman. After all, these are the same states whose civil orders were repeatedly disrupted by Iranian subversion and sponsorship of terrorism during the first decade after Iran’s Islamic revolution, and whose thriving economies rely on unimpeded access to the global commons. The events of the past decade have only exacerbated the smaller Gulf states’ endemic sense of insecurity. Iran has achieved a synergistic, sometimes even parasitic, relationship with the leadership of post-Saddam Iraq that, together with Tehran’s longstanding relationships with Syria and Lebanese Hizballah, greatly enables its bid for predominance in the heart of the Middle East. Today, the uncertainties surrounding the implications of regional flux have left Tehran simultaneously weakened and emboldened—a particularly dangerous combination for this particular array of Iranian leaders.

With Iran’s nuclear program advancing by the month and its efforts to tilt the regional balance in its favor growing more forceful, the small states of the Persian Gulf must face the distinct dilemma of preparing for the possible worst-case scenario of the nuclearization of their neighborhood, while participating ever more robustly in the international efforts to preclude that very possibility. In some respects, the Gulf states’ situation is unique. Unlike Israel, another small state that perceives an existential threat from Iran, the Gulf states cannot fall back upon either a presumptive nuclear deterrent or a primordial bond to the body politic of the world’s only remaining superpower. And in contrast to Iran’s other neighbors, the vast resources and history of ideological and territorial disputes between the Gulf states and Tehran significantly intensify the stakes. Even before the Gulf became the vital transportation corridor for global energy, the fault line in the regional balance of power had always run between the northern states and their southern rivals. The mere possibility that the north may gain a nuclear advantage is reshaping the security environment for Iran’s neighbors in the Gulf.

Because the threat of Iran looms large, the exigency of considering the widest possible array of alternative prospects for the evolution of this protracted crisis is important. This paper tackles the scenarios that successive American presidents have deemed unacceptable—an Iranian development or acquisition of a nuclear weapons capability or of nuclear weapons themselves—and the implications that such scenarios would have for the global nonproliferation regime and regional security, with a particular focus on the special challenges faced by Iran’s southern neighbors. To protect against threats along their borders, the Gulf states have traditionally hedged their bets by seeking balanced relations with their more powerful neighbors while cultivating extra-regional allies. That formula is already changing, as evidenced by a new assertiveness in Gulf states’ postures toward Tehran and a new creativity in deploying strategies for deterring and mitigating Iran’s efforts to extend its influence and/or destabilize its neighbors. The Gulf states must transform this tactical innovation into a full-fledged new hedging policy: one that deploys every possible tool to prevent a nuclear Iran while taking every possible step to prepare for such an eventuality.

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• Thinking the Unthinkable: The Gulf States and a Nuclear Iran

It seems the Senate could have a really hot summer. Majority leader Harry Reid (D-NV) has reportedly threatened to “go nuclear” this July—meaning that Senate Democrats would move by majority vote to ban filibusters of executive and judicial branch nominees. According to these reports, if Senate Republicans block three key nominations (Richard Cordray to head the Consumer Financial Protection Bureau, Thomas Perez at Labor, and Gina McCarthy at EPA), Reid will call on the Democrats to invoke the nuclear option as a means of eliminating filibusters over nominees.

Jon Bernstein offered a thoughtful reaction to Reid’s gambit, noting that Reid’s challenge is to “find a way to ratchet up the threat of reform in order to push Republicans as far away from that line as possible.” Jon’s emphasis on Reid’s threat is important (and is worth reading in full).  Still, I think it’s helpful to dig a little deeper on the role of both majority and minority party threats that arise over the nuclear option.

Before getting to Reid’s threat, two brief detours. First, a parliamentary detour to make plain two reasons why Reid’s procedural gambit is deemed “nuclear.” First, Democrats envision using a set of parliamentary moves that would allow the Senate to cut off debate on nominations by majority vote (rather than by sixty votes). Republicans (at least when they are in the minority) call this “changing the rules by breaking the rules,” because Senate rules formally require a 2/3rds vote to break a filibuster of a measure to change Senate rules. The nuclear option would avoid the formal process of securing a 2/3rds vote to cut off debate; instead, the Senate would set a new precedent by simple majority vote to exempt nominations from the reach of Rule 22. If Democrats circumvent formal rules, Republicans would deem the move nuclear. Second, Reid’s potential gambit would be considered nuclear because of the anticipated GOP reaction: As Sen. Schumer argued in 2005 when the GOP tried to go nuclear over judges, minority party senators would “blow up every bridge in sight.” The nuclear option is so-called on account of the minority’s anticipated parliamentary reaction (which would ramp up obstruction on everything else).

A second detour notes simply that the exact procedural steps that would have to be taken to set a new precedent to exempt nominations from Rule 22 have not yet been precisely spelled out.  Over the years, several scenarios have been floated that give us a general outline of how the Senate could reform its cloture rule by majority vote. But a CRS report written in the heat of the failed GOP effort to go nuclear in 2005 points to the complications and uncertainties entailed in using a reform-by-ruling strategy to empower simple majorities to cut off debate on nominations. My sense is that using a nuclear option to restrict the reach of Rule 22 might not be as straight forward as many assume.

That gets us to the place of threats in reform-by-ruling strategies. The coverage of Reid’s intentions last week emphasized the importance of Reid’s threat to Republicans: Dare to cross the line by filibustering three particular executive branch nominees, and Democrats will go nuclear. But for Reid’s threat to be effective in convincing GOP senators to back down on these nominees, Republicans have to deem Reid’s threat credible. Republicans know that Reid refused by go nuclear last winter (and previously in January 2009), not least because a set of longer-serving Democrats opposed the strategy earlier this year. It would be reasonable for the GOP today to question whether Reid has 51 Democrats willing to ban judicial and executive branch nomination filibusters. If Republicans doubt Reid’s ability to detonate a nuclear device, then the threat won’t be much help in getting the GOP to back down. Of course, if Republicans don’t block all three nominees, observers will likely interpret the GOP’s behavior as a rational response to Reid’s threat. Eric Schickler and Greg Wawro in Filibuster suggest that the absence of reform on such occasions demonstrates that the nuclear option can “tame the minority.”  Reid’s threat would have done the trick.

As a potentially nuclear Senate summer approaches, I would keep handy an alternative interpretation.  Reid isn’t the only actor with a threat: given Republicans’ aggressive use of Rule 22, Republicans can credibly threaten to retaliate procedurally if the Democrats go nuclear.  And that might be a far more credible threat than Reid’s. We know from the report on Reid’s nuclear thinking that “senior Democratic Senators have privately expressed worry to the Majority Leader that revisiting the rules could imperil the immigration push, and have asked him to delay it until after immigration reform is done (or is killed).” That tidbit suggests that Democrats consider the GOP threat to retaliate as a near certainty. In other words, if Republicans decide not to block all three nominees and Democrats don’t go nuclear, we might reasonably conclude that the minority’s threat to retaliate was pivotal to the outcome. As Steve Smith, Tony Madonna and I argued some time ago, the nuclear option might be technically feasible but not necessarily politically feasible.

To be sure, it’s hard to arbitrate between these two competing mechanisms that might underlie Senate politics this summer.  In either scenario—the majority tames the minority or the minority scares the bejeezus out of the majority—the same outcome ensues: Nothing. Still, I think it’s important to keep these alternative interpretations at hand as Democrats call up these and other nominations this spring. The Senate is a tough nut to crack, not least when challenges to supermajority rule are in play.

Event Information

The Joint Comprehensive Plan of Action (JCPOA) adopted by Iran and the P5+1 partners in July 2015 was an effort not only to prevent Iran from acquiring nuclear weapons but also to avert a nuclear arms competition in the Middle East. But uncertainties surrounding the future of the Iran nuclear deal, including the question of what Iran will do when key JCPOA restrictions on its nuclear program expire after 15 years, could provide incentives for some of its neighbors to keep their nuclear options open.

In their Brookings Arms Control and Non-Proliferation Series monograph, “The Iran Nuclear Deal: Prelude to Proliferation in the Middle East?,” Robert Einhorn and Richard Nephew assess the current status of the JCPOA and explore the likelihood that, in the wake of the agreement, regional countries will pursue their own nuclear weapons programs or at least latent nuclear weapons capabilities. Drawing on interviews with senior government officials and non-government experts from the region, they focus in depth on the possible motivations and capabilities of Egypt, Turkey, Saudi Arabia, and the United Arab Emirates for pursuing nuclear weapons. The monograph also offers recommendations for policies to reinforce the JCPOA and reduce the likelihood that countries of the region will seek nuclear weapons.

On May 31, the Brookings Arms Control and Non-Proliferation Initiative hosted a panel to discuss the impact of the JCPOA on prospects for nuclear proliferation in the Middle East. Brookings Senior Fellow and Deputy Director of Foreign Policy Suzanne Maloney served as moderator. Panelists included H.E. Yousef Al Otaiba, ambassador of the United Arab Emirates to the United States; Derek Chollet, counselor and senior advisor for security and defense policy at the German Marshall Fund; Brookings Senior Fellow Robert Einhorn; and Brookings Nonresident Senior Fellow Richard Nephew.

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• The Iran nuclear deal: Prelude to proliferation in the Middle East?

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• Uncorrected Transcript (.pdf)

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• 20160531_iran_nuclear_deal_transcript

In last summer’s congressional debate over the Iran nuclear deal—the Joint Comprehensive Plan of Action (JCPOA)—one of the more hotly debated issues was whether the deal would decrease or increase the likelihood that countries in the Middle East would pursue nuclear weapons.

Supporters of the JCPOA argued that, by removing the risk of a nuclear-armed Iran, it will reduce incentives for countries of the region to acquire nuclear arms. Opponents of the deal—not just in the United States but also abroad, especially Israel—claimed that the JCPOA would increase those incentives because it would legitimize enrichment in Iran, allow Iran to ramp up its nuclear capacity when key restrictions expire after 10 and 15 years, and boost the Iranian economy and the resources Iran could devote to a weapons program.

I strongly believe the JCPOA will significantly reduce prospects for proliferation in the Middle East (and as my colleague Richard Nephew explains in another post out today, there are things the United States and other powers can do to help reduce that prospect further). But uncertainties about the future of the JCPOA and the region will persist for quite some time—and these uncertainties could motivate regional countries to keep their nuclear options open. They may ask themselves a variety of questions in the years ahead: Will the JCPOA be sustainable over time? Will it unravel over concerns about compliance? Will it withstand challenges by opponents in Tehran and Washington? Will it survive leadership transitions in the United States and Iran? Will Iran ramp up its fissile material production capacities when key restrictions expire? Will it then break out of the JCPOA and seek to build nuclear weapons? Will Iran continue to threaten the security of its neighbors in the years ahead? And will the United States maintain a strong regional military presence and be seen by its partners as a reliable guarantor of their security?

I strongly believe the JCPOA will significantly reduce prospects for proliferation in the Middle East.

Richard and I studied how these and other questions might affect nuclear decision-making in the Middle East. In particular, we evaluated the likelihood that key states will pursue nuclear weapons, or at least enrichment or reprocessing programs that could give them a latent nuclear weapons capability. We focused on four states often regarded as potential candidates to join the nuclear club: Saudi Arabia, the United Arab Emirates, Egypt, and Turkey.

Saudi Arabia

Of the four, Saudi Arabia is the most highly motivated to pursue nuclear weapons. It sees Iran as an implacable foe that is intent on destabilizing its neighbors, achieving regional hegemony, and upending the Kingdom’s internal order. At the same time, the Saudis have lost much confidence in the U.S. commitment to the security of its regional partners. In part as a result, the new Saudi leadership has taken a more assertive, independent role in regional conflicts, especially in Yemen. But despite their reservations about the United States, the Saudis know they have no choice but to rely heavily on Washington for their security—and they know they would place that vital relationship in jeopardy if they pursued nuclear weapons.

The Saudis clearly have sufficient financial resources to make a run at nuclear weapons. But acquiring the necessary human and physical infrastructure to pursue an indigenous nuclear program would take many years.

Given the Kingdom’s difficulty in developing an indigenous nuclear weapons capability, speculation has turned to the possibility that it would receive support from a foreign power, usually Pakistan, which received generous financial support from Saudi Arabia in acquiring its own nuclear arsenal. But while rumors abound about a Pakistani commitment to help Saudi Arabia acquire nuclear weapons, the truth is hard to pin down. If such a Saudi-Pakistani agreement was ever reached, it was probably a vague, unwritten assurance long ago between a Pakistani leader and Saudi king, without operational details or the circumstances in which it would be activated. In any event, the Saudis would find it hard to rely on such an assurance today, when Pakistanis are trying to put the legacy of A.Q. Khan behind them and join the international nonproliferation mainstream. 

United Arab Emirates (UAE)

Like Saudi Arabia, the UAE believes Iran poses a severe threat to regional security and has become more aggressive since the completion of the JCPOA. And like the Saudis, the Emiratis have lost considerable confidence in the reliability of the United States as a security guarantor. But also like the Saudis, the Emiratis are reluctant to put their vital security ties to the United States in jeopardy.

[L]ike the Saudis, the Emiratis have lost considerable confidence in the reliability of the United States as a security guarantor.

Moreover, the Emiratis are heavily invested in their ambitious nuclear energy program—with efforts currently underway, with the help of a South Korean-led consortium, to construct four nuclear power reactors—and they know this project would be dead in the water if they opted for nuclear weapons.

The Emiratis have also been a leading regional supporter of nonproliferation. In their bilateral agreement for civil nuclear cooperation with the United States, they formally renounced the acquisition of enrichment or reprocessing capabilities (the so-called “gold standard”), effectively precluding the pursuit of nuclear weapons. After the JCPOA permitted Iran to retain its enrichment program, the UAE, faced with criticism domestically and from some Arab governments for having given up its nuclear “rights,” said it may reconsider its formal renunciation of enrichment. But subsequently, Emirati officials have made clear that their nuclear energy plans have not changed and that they have no intention to pursue enrichment or reprocessing.

Egypt

Egypt is on everyone’s short list of potential nuclear aspirants—in part because of its former role as leader of the Arab world and its flirtation with nuclear weapons in the Gamal Abdel Nasser years. But while Egypt and Iran have often been regional rivals, Egypt does not view Iran as a direct military threat. Instead, Egypt’s main concerns include extremist activities in the Sinai, the fragmentation of Iraq and Syria, disarray in Libya—and the adverse impact of these developments on Egypt’s internal security. The Egyptians recognize that none of these threats can be addressed by the possession of nuclear weapons.

Although Russia is committed to work with Egypt on its first nuclear power reactor, Cairo’s nuclear energy plans have experienced many false starts before, and there is little reason to believe the outcome will be different this time around, especially given the severe economic challenges the Egyptian government currently faces. Moreover, although Egypt trained a substantial number of nuclear scientists in the 1950s and 1960s, its human nuclear infrastructure atrophied when ambitious nuclear energy plans never materialized.

Turkey

Because of its emergence in the last decade as a rising power, its large and growing scientific and industrial basis, and its ambition to be an influential regional player, Turkey is also on everyone’s short list of potential nuclear-armed states. But Turkey has maintained reasonably good relations with Tehran, even during the height of the sanctions campaign against Iran. Although the two countries have taken opposing sides in the Syria civil war, Turkey, like Egypt, does not regard Iran as a direct military threat. Indeed, Ankara sees instability and terrorism emanating from the Syrian conflict as its main security concerns—and nuclear weapons are not viewed as relevant to dealing with those concerns.

Current tensions with Russia over Turkey’s November 2015 shoot-down of a Russian fighter jet are another source of concern in Ankara. But the best means of addressing that concern is to rely on the security guarantee Turkey enjoys as a member of NATO. While Turkish confidence in NATO has waxed and waned in recent decades, most Turks, especially in the military, believe they can count on NATO in a crisis, and they would be reluctant to put their relationship with NATO at risk by pursuing nuclear weapons.

Former nuclear aspirants

For the sake of completeness, our study also looked at regional countries that once actively pursued nuclear weapons but were forced to abandon their programs: Iraq, Libya, and Syria. But we concluded that, given the civil strife tearing those countries apart, none of them was in a position to pursue a sustained, disciplined nuclear weapons effort.

Bottom line

Our study found that the Iran nuclear deal has significantly reduced incentives for countries of the Middle East to reconsider their nuclear options. At least for the foreseeable future, none of them is likely to pursue nuclear weapons or even latent nuclear weapons capabilities—or to succeed if they do. 

Editors’ Note: Bob Einhorn and Richard Nephew spoke about their new report at a recent Brookings event. You can see the video from the event here.

Was the Iran nuclear deal, signed last summer, a prelude to proliferation across the Middle East? This is a question that Brookings Senior Fellow Robert Einhorn and Non-resident Senior Fellow Richard Nephew explore in a new report. At an event to discuss their findings—moderated by Brookings Deputy Director of Foreign Policy and Senior Fellow Suzanne Maloney and with panelists Derek Chollet and H.E. Yousef Al Otaiba—Einhorn and Nephew argued that none of the Middle East’s “likely suspects” appears both inclined and able to acquire indigenous nuclear weapons capability in the foreseeable future. They also outlined policy options for the United States and other members of the P5+1.

Einhorn described the incentives and capabilities of Egypt, Saudi Arabia, Turkey, and the United Arab Emirates for acquiring nuclear weapons. He argued that, while both Saudi Arabia and the UAE a) consider Iran a direct military threat, b) have concerns about the U.S. commitment to the security of the region, and c) have sufficient financial resources, they recognize that they have no choice but to rely on the United States for their security and are unwilling to jeopardize that relationship by seeking nuclear weapons. Einhorn also said that both Egypt and Turkey do not view Iran as a direct military threat and are more preoccupied with instability on their borders and internal security, concerns that cannot be addressed by possession of a nuclear weapons capability.

Nephew outlined policy recommendations, including measures to ensure strict implementation of the JCPOA, greater intelligence sharing and security cooperation with Middle East allies, and means of fostering IAEA-supervised regional arrangements that would encourage peaceful nuclear energy development and limit potentially destabilizing nuclear activities. Nephew also asserted that some elements of the JCPOA, such as online monitoring of nuclear facilities, could be applied to other nuclear energy programs in the region to enhance transparency. 

Derek Chollet of the German Marshall Fund argued the United States must deter Iran and reassure U.S. allies by maintaining a robust military presence in the region, planning a range of U.S. responses to destabilizing Iranian activities, and ensuring that U.S. forces have the weapons systems and personnel required for scenarios involving Iran. He suggested that the United States and its Middle East allies continue regular summit meetings on security and broader partnership issues, and possibly formalize security cooperation by establishing a dedicated regional security framework. 

Emirati Ambassador to the United States Yousef Al Otaiba emphasized that, to many of the countries in the region, Iran poses a threat wider than just its nuclear activities. He suggested that the JCPOA will be judged on the degree to which the United States and its allies address Iran’s destabilizing behavior outside of the nuclear file, such as Tehran’s support for Hezbollah and the Houthis, as well as its ballistic missile activities. Al Otaiba said that, though he has seen some efforts by the Obama administration to push Iran on its regional behavior, it has sent a mixed message overall, with senior U.S. officials also encouraging European banks to invest in Iran. The ambassador asserted that rigorous enforcement of the JCPOA will be critical to convincing Iran not to eventually proceed to build nuclear weapons.

On Saudi Arabia, Einhorn noted that although the Obama administration supported the Saudi military campaign in Yemen, there was a risk that the Kingdom would overreact to its regional security challenges. He suggested that the United States pursue a dual-track approach: counter provocative Iranian behavior and defend the security interests of its regional partners, while at the same time seeking a resolution of regional disputes and encouraging Saudi Arabia and Iran to find ways of reducing tensions between them.

On the possibility that Iran would rapidly scale up its enrichment program, Einhorn acknowledged that while Tehran can legally do so under the JCPOA in 10 to 15 years, it will not have a strong civil nuclear rationale since it will be able to acquire nuclear fuel from Russia and other suppliers. Furthermore, Iran’s progress in centrifuge research and development may not be as rapid as Iran currently anticipates. Moreover, even if Iran elects to ramp up its enrichment program down the line, the JCPOA and Nuclear Non-Proliferation Treaty (NPT) will bar it from pursuing nuclear weapons, and monitoring arrangements still in place will provide warning and enable the United States to intervene and prevent Iran from building nuclear weapons.

On reaching a regional accommodation that includes Iran, Al Otaiba indicated that the UAE would have much to gain, especially economically, from a better relationship with Tehran. He said the UAE and others in the region would like to try to engage with Iran to reduce tensions—but Iran, for its part, seems unwilling.

On prospects for a U.S.-Saudi civil nuclear cooperation agreement, Einhorn said that progress on such an agreement has stalled due to Saudi reluctance to formally renounce enrichment, something the United States has so far insisted on. He suggested that Washington should be prepared to relax the so-called “gold standard” (i.e., a formal renunciation of on enrichment and reprocessing) and instead accept an approach that would still discourage Saudi fuel cycle programs, such as giving Riyadh the right to pursue enrichment but allowing the United States to cease its nuclear cooperation if the Kingdom exercised that right. On the UAE’s civil nuclear program, Al Otaiba affirmed that the Emiratis continue to value the “gold standard” barring enrichment which is enshrined in the U.S.-UAE civil nuclear agreement, and have no plans to change their position on enrichment.

Education is at a critical juncture in many nations around the world. It is vital for student learning, workforce development, and economic prosperity. For example, research in Turkey has found that raising the compulsory education requirement from five to eight years increased the percentage of women having eight years of school by 11 percentage points, and had a variety of positive social consequences.

Yet despite the emergence of digital learning, most countries still design their educational systems for agrarian and industrial eras, not the 21st century. This creates major problems for young people who enter the labor force as well as teachers and parents who want children to compete effectively in the global economy.

In this paper, Darrell West examines how mobile devices with cellular connectivity improve learning and engage students and teachers. Wireless technology and mobile devices:

• Provide new content and facilitate information access wherever a student is located
• Enable, empower, and engage learning in ways that transform the environment for students inside and outside school
• Allow students to connect, communicate, collaborate, and create using rich digital resources, preparing them to adapt to quickly evolving new technologies
• Incorporate real-time assessment of student performance
• Catalyze student development in areas of critical-thinking and collaborative learning, giving students a competitive edge

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The breakthrough therapy designation (BTD) program was initiated by the U.S. Food and Drug Administration (FDA) in 2012 to expedite the development of treatments for serious or life-threatening illness that demonstrate “substantial improvement” over existing therapies. The program has since become a widely supported mechanism for accelerating patient access to new drugs. As of March 2015, FDA has received a total of 293 requests for BTD. However, it has granted just  82 (28%), which indicates an ongoing lack of clarity over what exactly meets the criteria for the designation.

On April 24, the Center for Health Policy at Brookings convened a public meeting to explore the designation’s qualifying criteria and how FDA applies those criteria across therapeutic areas. Panelists used real-world and hypothetical case studies to frame the discussion, and highlighted major considerations for the application process, the FDA’s evaluation of the evidence, and the key factors for acceptance or rejection. The discussion also identified strategies to ensure that qualifying criteria are well understood. Here are the five big takeaways:

1.  The BTD program is viewed positively by drug companies, researchers, advocates, and others 

Across the board, participants expressed enthusiasm for the BTD program. Industry representatives noted that their experience had been extremely positive, and that the increased cooperation with and guidance from FDA were very helpful in streamlining their development programs. Receiving the designation can also raise a drug company’s profile, which can facilitate additional investment as well as clinical trial patient recruitment; this is particularly important for smaller companies with limited resources.

Patient and disease advocates were likewise supportive, and expressed hope that the early lessons learned from successful breakthrough therapy approvals (which have been mostly concentrated in the oncology and antiviral fields) could be translated to other disease areas with less success. However, while BTD is an important tool in expediting the development of new drugs, it is just one piece of broader scientific and regulatory policy landscape. Accelerating the pace of discovery and development of truly innovative new drugs will depend on a range of other factors, such as developing and validating new biomarkers that can be used to measure treatment effects at an earlier stage, as well as establishing networks that can streamline the clinical trial process. It will also be important to develop effective new approaches to collecting, analyzing, and communicating information about these treatments once they are on the market, as this information can potentially be used by FDA, providers, and patients to  further improve prescription drug policy and medical decision-making.

2.  BTD requests far outnumber those that actually meet the qualifying criteria

Since the program began, less than 30 percent of requests have received BTD designation. A substantial majority were denied at least in part due to either a lack of data or problems with the quality of the data, or some combination of the two. For example, some sponsors requested the designation before they had any clinical data, or submitted the request using clinical data that was incomplete or based on flawed study designs. Many requests also failed to meet the Agency’s bar for “substantial improvement” over existing therapies.

One reason for the high denial rate may be a lack of a clear regulatory or statutory bar that could be used as a definitive guide for sponsors to know what is needed to qualify for the designation. BTD denials are also confidential, which means that sponsors effectively have nothing to lose by submitting a request. Going forward, manufacturers may need to exercise more discretion in deciding to request the designation, as the process can be resource- and time-intensive for both sides.

3.  There is no single threshold for determining what defines a breakthrough therapy

About 53 percent of the 109 total BTD denials were due at least in part to the fact that the drug did not represent a substantial improvement over existing therapies. During the day’s discussion, FDA and sponsors both noted that this is likely because the criteria for BTD are inherently subjective. In practice, this means there is no clear threshold for determining when a new therapy represents a “substantial improvement” over existing therapies. Designation decisions are complex and highly dependent on the context, including the disease or condition being targeted, the availability of other treatments, the patient population, the outcomes being studied, and the overall reliability of the data submitted. Given the multiple factors at play, it can be difficult in some cases to determine when a new product is potentially “transformational” as opposed to “better,” especially for conditions that are poorly understood or have few or no existing treatments. In making its determinations, FDA considers the totality of the evidence submitted, rather than focusing on specific evidentiary requirements.

4.  Early communication with FDA is strongly recommended for BTD applicants

Roughly 72 percent of the BTD denials related at least in part to trial design or analysis problems, which led several people to suggest that sponsors engage with FDA prior to submitting their request. Though there are several formal mechanisms for interacting with the agency, informal consultations with the relevant review division could help sponsors to get a better  and much earlier sense of what kind of data FDA might need. This early communication could both strengthen viable BTD requests and reduce the number of frivolous requests.

5.  FDA may need more resources for implementing the BTD program